Canine Neoplasia

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REVIEW- cancer chemoprevntative compounds and canine cancer

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·      NSAIDS: inactivate COX (chemoprev for TCC)– mitogens, tumor promoters and growth factors upreg COX-2. Piroxicama nd meloxicam inhibit COX-2 and induce apoptosis in cell culture

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Vp

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·      Tx of mammary CA w/ COX-2 inhibitor, blocks PGE2 synth and v cell prolif

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·      PG bind specific receptros -> signaling thru receptor EP2 impt in tumorigenesis (disruption of EP1 and EP3 had no effect)

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·      EP2 is g-prot > increases cAMP > activation of PKA sig path > increase amphiregulin, enhances RAS-MAP path and transactivationof PPARg receptor path, also P GSK-3band alters APC/b-catenin / TCF pathto reg cell prolif, angiogenesis, and apoptosis

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·      Conjugated linoleic acid decreases EP2 expression in mammary cells

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·      LOX activity implicated in several types of neoplasia

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·      NSAID-activated gene-1 (NAG-1)—broad activity in infl and cancer-

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·      NAG1 expression â TNFa in Mf. inhibits prolif of primitive hematopoietic precursors

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·      NAG-1 suppresses tumor growth in mouse models of cancer – induced by several NSAIDs

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·      Early growth response-1 (EGR-1)= tumor suppressor gene. Is downreg in tumors- induced by tumor suppressor prot

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·      TSP-1 and ATF-3 are also á by NSAIDs – both attenuate invasion of tumor cells

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·      PPARg is ligand activated transcription factor – forms complex with retinoid X receptor and complex binds PPAR response element- fxns as reg of cellular differentiation, apoptosis, infl, lipid metabolism, and metabolic dz. Activation responsible for enzyme indxn, peroxisome prolif, liver enlargement and anti-infl

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·      Obesity á risk of dev cancer

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·      CLA reg COX-2 and EP2 prot expression

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·      Vit D can inhibit cell prolif, induce differentiation, promote apoptosis

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·     Calcitriol (VDR agonist) when added to TCC, SCC, and ACA inhibits cell growth via cell cycle arrest (k9 tumors)

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Influence of catechol-O-methyltransferase (COMT) genotypes on Px of K9 mammary tumors

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·     Involved in inactivation of catechol estrogens, are metabolites w/ carcinogenic prop

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Vp

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·     Bitches with both genetic variations simultaneously are more likely to dev recurrence of mammary lesions

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·     Increased prolonged exposure of mammary tissue to estrogen = á risk for mammary cancer – promote epith cell growth and are precursors for mutagenic estrogen metabolites

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COX-2 expresssion in k-9 mamary CA: corr w/ angiogenesis and overall survival

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·     CD31 to measure microvessel density

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Vp

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·     Cox-2 expression corr w/ CD31, but did not corr w/ tumor type

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·     Cox-2 and CD31 rel to worse px

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·     Hypoxia, IL-6, ras, VEGF lead to á COX-2 expression

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·     Tumor invasiveness mediated tjru increased activity of MMP-9 and MMP-2

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Estrogens metabolism associated with polymorphisms: influence of COMY G482a genotype on age at onset of k9 mammary tumors

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·     COMT=Catechol-O-methyltransferase> impt enzyme participating in inactivation of carcinogenic estrogen metabolites.

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Vp

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·     Animals with variant allele are 3X more likely to develop mammary tumors when >9yo.

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Plasticity of cloned canine mammary spindle cell tumor , OSA and CA cells

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·     All give rise to tumor types distinct from original

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Vp

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Expression of p63 and CK5 in mixed tumors of canine mammary gland provides new insights into histogenesis of these neoplasms

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·     Mixed tumors of k9 mammary are myoepith origin

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Vp

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·     CK5 and p63 co-expression in myoepith of benign mixed tumors and in squamous differentiation of carcinoma arising from benign mixed tumors

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·     CK5 marker of basal epith cells and myoepith in k9 mixed tumors

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·     Basal epith cells may rel to origin of epith component of mixed tumors of k9 mammary gl

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·     Normal mammary= luminal layer : ck7, 8, 18, 19

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·     Basal epith = ck5, 14,17, NOT SMA

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·     Myoepith cells CK5, 14, 17, p63, SMA

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Prospective analysis of IHC determined ERα and Progesterone receptor expression and host and tumor factors as predictors of disease free pd in k9 mammary tumors

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·     Benign = ERα + / PR +

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Vp

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·     Malignant = ERα - / PR +

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·     Tumor size and histo grading were independent prognosticators

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Expression of maspin in k9 mammary tumors

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·     Maspin is serine protease inhibitor that inhibits tumor invasion and mets—is consistently expressed by mammary epith cells

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Vp

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·     Sensitive marker of normal and neoplastic myoepith that does not stain stromal myofibroblasts

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Expression of Connexins 26 and 43 in Canine Hyperplastic and neoplastic mammary glands

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·     Gap jxns composed of connexins

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Vp

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·     Expression and distribution of connexins and E-cadherin are inversely correlated to cell prolilferation in malignant mammary neoplasms of dogs and may be rel to mor aggressive histo and behavior

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Epo receptor expression in k9 mammary tumor : IHC study

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·     EPO and EPOR expressed in several neoplastic cell lines and solid tumors

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Vp

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·     EPOR expression in k9 mammary gl tumor

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·     Binding of EPO to receptor inhibits apoptosis

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COX-2 expression assoc w/ histo tumor type in k9 mammary CA

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·     Anaplastic CA had ^ COX-2 staining distribution, intensity and index compared to those for ACA

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Vp

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·     Direct assoc btw COX-2 expression and tumor histo subtype in k9 mammary CA

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Tumor assoc Carbohydrate Ag: Sialyl Lea and T/Tn Ag in k9 mammary tumors

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·     Only T and Tn Ag assoc w/ malignant xformation of mammary gl cells & are potential diagnostic markers

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Vp

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·     Tumor assoc carbohydrates divided into 2 major groups ;

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·     1) modified lacto-series type1 or type2 chains, Sialyl Lea and sialyl Lex

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·     2) core carbohydrate strx of O-linked mucin-type, T and Tn Ag.

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IHC char of mammary SCC in dog

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·     Pancytokeratin and CK19 were most useful to establish histogenesis.

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Jvdi

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·     Epidermal squamous: PanCK + / CK19 –

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·     Gland derived: PanCK + / CK19 +

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Serum acute phase protein concentrations in female dogs with mammary tumors

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·     Positive APP = C-reactive protein, SAA, Hp

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Jvdi

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·     Negative APP = Albumin

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·     Alb decreased in animals with mets and concomitant dz

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·     Acute phase response stim in females with mammary tumors b/c of diff factors incl mets, lg size of primary mass, and ulceration or secondary infl of neoplasm

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Microsatellite instability in k9 mammary tumors

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·     Lo-level MSI oft obs.

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JVIM

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·     Hi-level MSI infreq in mammary tumors

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Mammary gland tumors in male dogs

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·     Estrogen receptor expression strong in majority of tumors

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Jvim

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·     Mammary gl tumors in male dogs rare, usu benign, surgery to tx

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↓PTEN prot expression and px implications in canine and Fe Mammary tumors

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·     K9 mammary tumors = sig corr btw losso f PTEN excpression and simple carcinoma histotype, lymphatic vessel invasion, LN mets, distant organ mets, tumor dedifferentiation, tumor recurrence, and shorter survival,

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Vp

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·     Fe mammary tumors= corr btw loss of PTEN and lymphatic vessel invasion

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·     PTEN inhibits P of PI2P to PI3P by antagonizing PI3Kand inhibiting downstream cascade. > cell prolif and survival via PKB path

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·     PTEN also stabilizes jxns that interact with guanulate kinase inverted family> loss of this fxn corr w/ ↑ invasiveness of tumor cells

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·     PTEN also interacts with p53 and increases DNA binding, and transcriptional activity

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Mitotic index predictive for survival for k9 cutaneous MCT

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·     Mitotic index = # mitosis / 10 HPF

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Vp

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·     MI < 5 increased survival time

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·     MI>5 decreased survival time

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Cellular proliferation in canine cutaneous MCT: assoc w/ c-KIT and role in Px

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·     Increased ki67 and AgNOR assoc with decreased survival

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Vp

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·     MCT with aberrant KIT protein localization or internal tandem duplication c-KIT mutations are assoc with increased cellular proliferation

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Widespread mismatch repair protein expression in k9 MCT

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·     Results DO NOT support that MMR defects predispose to MCT and mech for inheritance is unclear

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Vp

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Study of mutations in c-kit gene in dogs with mastocytoma

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·     Mutations in intracellular juxtamembrane domain of ckit gene

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Jvdi

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·     Substitutions found in dogs with grade I or II MCT

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·     Deletion in dog with grade II

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Nuclear morphometry in cytopathology: px indicator for k9 cutaneous MCT

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·     Corr btw mean nuclear area and survival

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Jvdi

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·     Proliferation markers and KIT expression patterns also px indicators

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IHC detection of Protein Gene Product 9.5 (PGP 9.5) in k9 epitheliotropic t-cell LSA (mycosis Fungoides)

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·     PGP 9.5 is an ubiquitin COOH-terminal hydrolase expressed in variety of epith and mesenchymal tumors.

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Vp

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·     PGP 9.5 IHC DID NOT predict tumor behavior

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Anemia assoc with decreased survival time in dogs with LSA

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·     Cancer rel anemia more freq in dogs with LSA than in controls or dogs with OSA.

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Jvim

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·     No effect of anemia on remission time in dogs with LSA

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t-cell LSA with eosinophilic infiltration involving the intestinal tract

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·     LSA of intestinal origin resemble MCT of intestinal origin with respect to cell strx and eos infiltration

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Vp

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·     IHC to Dx

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·     Majority of k9 intestinal LSA are t-cell origin

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·     Small to med sized LSA = epitheliotoropism

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·     Mod to lg LSA w/w/o epitheliotropism

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Canine Indolent Nodular LSA

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·     Indolent canine lymphoid proliferation primarily b-cell

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Vp

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·     Marginal zone LSA in LN and spleen

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·     Mantle cell LSA > solitary splenic masses

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·     Follicular LSA in LN

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·     Indolent LSA arise on bkgrd of follicular lymphoid hyperplasia, and include follicular, mantle cell, and marginal zone LSA of b-cell type.

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·     Lo-mitotic rate and slow progression—in advanced stages lose follicle related strx

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Inactivation of the p16 CDK Inhibitor in hi-grade k9 non-hodgkins t-cell LSA

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·     Deletion of p16 increases tumor cells with Rb phosphorylation at canonical CDK4 sites.

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Vp

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·     Rb phos was seen in hi grade B-cell NHL assoc with c-Myc overexpression

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·     P16 deletion / inactivation almost exclusive to hi-grade t-cell NHL

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·     CDK4 controls transition of activated T cells from G0 to G1 and from G1 to S phase.

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Antioxidant status and biomarkers of oxidative stress in dogs with LSA

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·     Dogs with LSA have altered oxidant and antioxidant concentrations and status of some of these normalize after remission

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Jvdi

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Prevalence and px impact of hypocobalaminemia in dogs w/ LSA

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·     Hypocobalaminemia uncommon, assoc w/ poor outcome

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Javma

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·     Dogs unable to synth cobalamin (req for nucleic acid synth, hematopoiesis)

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IHC and histochem stain for differentiating k9 cutaneous round cell tumors

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·     Mast cells + tryptase Ag and chymase activity

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Vp

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·     Chymase in tumor and non-tumor cells

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·     Serotonin not detected in most MCT

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·     Histiocytomas + CD18 and MHC II (also LSA-therefore use CD3 and cd79A to differentiate)

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·     3 types of mast cells: chymase only, tryptase only, or chymase and tryptase

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Survival of dogs following surgical excision of histologically well-differentiated melanocytic neoplasms of the mucous membranes of the lips and oral cavity

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·     Prolonged survival expected if tumor well differentiated with local excision.

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Vp

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Histo and epidemiologic basis for px considerations in k9 melanocytic neoplasia

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·     Negative determinants incl:

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Vp

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·     Mets

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·     Mitotic index

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·     Nuclear atypia

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·     Tumor score

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·     Increasing size / volume

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·     Presence of deep infl

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·     Intralesional necrosis

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·     Age impt in skin tumors

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·     Age and jxn activity for feet and lips

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·     Nuclear atypia most accurate prediction of behavior

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IHC char and eval of px factors in canine oral melanomas with osteocartilaginous differentiation

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·     Osteocartilaginous differentiation rare in oral melanoma

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Vp

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·     Osteocartilaginous area + for S100 and melan A

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·     Clin course sim to other melanomas in oral cavity

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Expression of monocarboxylate transporter 1 in oral and ocular canine melanocytic tumors

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·     In hypoxia, tumor cells upreg glycolysis and gen more lactate

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Vp

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·     MCT-1 = major prot

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·     Most oral melanomas stain for mct1 in membrane, ocular were negative

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·     Increased MCT1 in oral melanomas may reflect the different biology from ocular melanomas

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Histo features and clin outcomes of melanomas of lip, haired skin, and nail bed in dogs

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·     All nail bed melanomas had histo features of malignancy and all invaded 3rd phalanx

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Jvdi

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Mitotic index predictive for survival for k9 cutaneous MCT

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·     Mitotic index = # mitosis / 10 HPF

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Vp

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·     MI < 5 increased survival time

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·     MI>5 decreased survival time

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·     MI predictor of overall survival for dogs with cutaneous MCT

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Cellular proliferation in canine cutaneous MCT: assoc w/ c-KIT and role in Px

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·     Increased ki67 and AgNOR assoc with decreased survival

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Vp

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·     MCT with aberrant KIT protein localization or internal tandem duplication c-KIT mutations are assoc with increased cellular proliferation

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Assessment of COX-2 expression in k9 HSA, histiocytic sarcoma and MCT

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·     K9 HSA, HS and MCT DO NOT express COX-2

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Vp

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Mammary gland tumors in male dogs

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·     Estrogen receptor expression strong in majority of tumors

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Jvim

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·     Mammary gl tumors in male dogs rare, usu benign, surgery to tx

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Mutations of Phosphate and Tensin Homolog deleted from Chromosome 10 in k9 HSA

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·     Point mutations or deletions of PTEN C-term in k9 HSA

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Vp

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Histo grade predicts recurrence for marginally excised canine subcutaneous soft tissue sarcomas

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·     Clean margins predict non-recurrence

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Vp

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·     Tumor recurrence did not significantly reduce survival time

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Cytokeratin and vimentin co-expression in k9 1° pulm epith neoplasms

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·     ACA (+) CK, few (+) for CK and Vim

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Jvdi

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·     Papillary aca all vim (-)

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·     Anaplastic pattern has more vim

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·     Ck and vim co-expression occus in k9 1° pulm epith tumors

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·     CK and vim (+) : mesothelioma, anaplastic CA, amelanotic melanoma, renal CA, prostatic CA, HCC, fe bronchogenic ACA

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IHC Expression of VEGF-R assoc with tumor cell proliferation in k9 cutaneous SCC and trichoepitheliomas

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·     VEGF and VEGF-R2 may promote tumor cell prolif in trichoepitheliomas and SCC

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Vp

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·     Only VEGF-R2 is capable of angiogenesis

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Expression of VEGF, Basic fibroblast growth factor and their receptors (Flt-1, Flk-2, and Flg-1) in k9 vascular tumors

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·     VEGF receptors = flt-1, flk-1

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Vp

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·     bFGF receptor= flg-1

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·     VEGF, bFGF, flt-1 and flk-1 + in HSA

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·     hemangiomas =weak expression of VEGF

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·     HSA with intense flk-1 had hi prolif activity

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VEGF mRNA expression and peritumoral edema in k9 primary CNS tumors

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·     Increased VEGF predominantly in hi-grade astrocytic (grade IV) and oligodendroglial (grade III) tumors.

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Vp

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·     Lower expression in lower grade tumors.

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·     All 3 VEGF isoforms present- VEGF 164 predominant isoform in tumors with highest VEGF expression

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·     VEGF induces vascular permeability

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Ki-67 and VEGF in k9 intracranial meningiomas

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·     VEGF is predictive marker for survival in dogs with intracranial meningiomas

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Jvim

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·     Ki-67 (MIB-1 Ab) shows cell prolif but does not predict outcome

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MMP-2 and MMP-9 expression in k9 and fe meningioma

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·     Highest values of MMP-2 in psammomatous and MMP-9 in meningothelial tumor

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Vp

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·     No sig corr btw MMP and reverse transcriptase

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Spectrum of k9 cutaneous perivascular wall tumors: characterization

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·     Dx based on vascular growth patterns: staghorn, placentoid, perivascular, whorling, bundles) and IHC for smooth m. markers and cell membrane ganglioside

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Vp

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·     Preferential acral location

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·     Cytology= mod to hi cellularity, cohesive groups of cells, caps and bi-to multinucleated cells

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·     Smoothelin, heavy caldesmon, desmin, myosin, calponin, and membrane ganglioside were most valuable markers to dx PWT

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·     Progressive increase of vascular caliber, subendothelial lining cells convert from pericytes in caps to myopericytes in pre and post cap compartments, and in mature sm m cells in arteries and large veins

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·     Pericytes (+)= vimentin, +/- pan-actin, alpha SMA,

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·     Myopericytes (+) for above and desmin and calponin

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·     Sm M cells (+) = smoothelin and heavy caldesmon

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Comparative aspects and clin outcomes of k9 renal HSA

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·     Renal HSA not as bad as splenic, cardiac, retroperitoneal HSA

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Jvim

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Alk Phos to differentiate OSA from other vimentin (+) tumors

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·     ALP is highly sensitive and fairly specific marker in Dx of OSA

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Vp

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Hyalinizing Pancreatic ACA in dogs

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·     Histo= tubules and acini with bright eos granular apical cyto

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Vp

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·     Lumina and tumor stroma cont abundant hyaline material resembling amyloid

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·     (-) = amyloid A, Ig light chains, amylin, laminin, and a1-antitrypsin

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Nasal and paranasal ACA with neuroendocrine differentiation in dogs

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·     None of CA had cytological or histo features indicative of neuroendocrine differentiation, yet some (+) for Synpt and chromogranin A

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Vp

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Canine carcinosarcoma in head

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·     Carcinomatous cells resemble SCC

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Vp

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·     Sarcomatous cells show osteoid matrix (OSA)

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Usefulness of Thyroid Transcription Factor-1 IHC staining in dDx of primary pulmonary tumors in dogs

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·     TTF-1 (+) in bronchioloalveolar CA and bronchogenic CA

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Vp

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·     TTF-1 is moderately sensitive marker for k9 pulmonary epith tumors

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·     Thyroglobulin-prod cells, C-cells, and parathyroid cells express TTF-1

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·     In lung TTF-1 activates surfactant proteins and Clara cell secretory protein gene promoters

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·     TTF-1 nec for lung epith morphogenesis

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K9 hepatic neuroendocrine CA

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·     All (+) for NSE, chromogranin A, and synpt.

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Vp

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·     EM (+) for neurosecretory granules

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·     Chromogranin alone is not as useful in dogs

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Expression of embryonic TF Oct4 in k9 neoplasms- potential marker for stem cell subpops in neoplasia

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·     Oct4 assoc with pluripotent or stemlike cells

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Vp

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·     Oct4 expressed during embryogenesis- developmentally regulated

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·     Expression down reg as surrounding cells differentiate into trophoectoderm

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IHC detection of multiple myeloma 1 / IFN regulatory factor 4 (MUM1/IRF4) in k9 plasmacytoma

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·     MUM1/IRF4 involved in lymphoid cell differentiation, esp plasma cells

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Vp

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·     Ab to MUM1:

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·     specific for plasmacytomas

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·     Superior to CD79a and CD20 for ID of k9 plasmacytomas in formalin fixed paraffin embedded tissue

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·     LSA that express MUM1 are few and are usu of b-cell origin

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·     Other k9 leukocytic and melanocytic tumors do not express MUM1/IRF4

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·     Plasmacytomas oft found on lips, pinnae, digits, and chin- most benign

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·     (+) for CD45 and IgG, A, or M

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Detection of k9 oral papillomavirus DNA in conjunctival epith hyperplastic lesion in dogs

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·     ISH (+) for COPV within nuclei of hyperplastic epith

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Vp

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·     Spontaneous immune-med regression

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·     SCC of skin and gingival rarely assoc w/ k9 papillomavirus infxn

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Inflammatory myofibroblastic tumor in dogs

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·     Well demarcated

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Vp

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·     Bland spindle cells with numerous LPC scattered

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Choroid plexus tumor in dogs

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·     CSF protein concentration increased in choroid plexus CA than in choroid plexus papilloma

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Jvim

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Regulation of cox-2 expression in k9 prostate CA—Increased COX-2 expression is NOT related to inflammation

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·    

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Jvim

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Androgen receptor CAG repeat polymorphisms in k9 prostate cancer

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·     Short CAG-1 repeats in androgen receptor gene assoc with increased risk of dev k9 prostate cancer

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Jvim

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K9 hemophagocytic histiocytic SA- prolif disorder of CD11d+ macrophages

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·     Histiocytic disorders have prolif of dendritic cells of either Langerhan's or interstitial lineage

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Vp

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·     Coombs (-) anemia, decreased plt, decreased alb

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·     Diffuse splenomegaly with ill-defined masses

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·     Histo lesions in spleen, liver, lung, BM

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·     Histiocytes erythrophagocytic

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·     Well differentiated to atypical with atypia more prevalent in spleen than BM

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·     Tumors arose from splenic red pulp and BM macrophages

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Px significance of intratumoral microvessel density in k9 soft tissue SA

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·     IMD is of px value for histo grade, features, cellular prolif (AgNOR), and mets likelihood of k9 STS esp when using FVIII-RA as marker

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Vp

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Uveal spindle cell tumor of blue-eyed dogs- IHC

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·     All tumors in iris w/w/o ciliary body involvement- composed of spindle cells arranged in fascicles and whorls

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Vp

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·     All (+) for vimentin and s-100

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·     All (-) for SMA, desmin, melan A, and MITF-1

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·     Schwannoma

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·     Other common mets spindle cell tumors of eye= HSA, OSA, mets malig melanoma, anaplastic tumors of undetermined origin

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Microarray analysis of differentially expressed genes of primary tumors in the k9 CNS

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·     Found differentially expressed genes unique to either meningiomas or glial tumors

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Vp

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·     Meningiomas most common- most intracranial and arise from arachnoid cells

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IHC dx of k9 ovarian epithelial and granulosa cell tumors

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·     Normal ovary: surface epith (+): CK7, CKAE1/AE3, vimentin / (-) inhibin a

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Jvdi

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·     Granulosa cells (-) for CK7 / (+) inhibin a

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Evaluation of factors assoc with survival of dogs w/ untreated nasal carcinomas

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·     Epistaxis (+), had increased hazard of dying

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Javma

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K9 intracranial primary neoplasia

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·     Meningiomas, astrocytoma, oligodendroglioma, pnet, histiocytic sarcoma, vascular hamartoma

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Jvim

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·     Most tumors within telencephalon

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·     Brachycephalic breeds have ^ risk

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Expression of the tumor suppression genes NF2, 4.1B, and TSLC1 in k9 meningiomas

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·     No assoc btw tumor grade, subtype, or location and tumor suppressor gene expression

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Vp

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·     Loss of these tumor suppressor genes is freq in k9 meningiomas and may be early event in tumorigenesis

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Localized, plexiform, diffuse, and other variants of neurofibroma in dogs, horses and chicken

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·     Schwannoma = highly and poorly cellular areas of fusiform neoplastic schwann cells in stroma that is collagenous and scant (antoni A) or myxoid and abundant (antoni B) – also with nuclear palisading, verocay bodies and hyalinized microvessels. S-100 (+)

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Vp

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·     Neurofibromas are a mixture of schwann cells, perineurial cells and fibroblasts

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·     Very slender, elongated cells with buckled or wavy nuclei in fibromyxoid stroma with thin wire-like collagen fibers

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Solitary intracerebral plasmacytoma in A dog

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·     (+): vimentin, CD18, CD79a, λ light chain

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Vp

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Expression of connexins in normal and neoplastic k9 bone

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·     Main connexin involved in dev, differentiation, and reg of bone is connexin 43

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Vp

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·     Cx 46 is also expressed mostly within trans-golgi rgn

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·     Alterations in expression pattern and aberrant location assoc w/ oncogenesis, showing def gap jxn intercellular communication in neoplastic tissues

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·     Cx43 normally in intercellular membranes – in tumor, in cell membrane and cyto

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·     + corr btw cx43 expression and collagen deposition

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·     Cx46 lower levels of expression in neoplastic bone than in normal

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·     Connexins compose gap jxns

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Expression of hepatocyte growth factor and proto-oncogene receptor c-Met in k9 OSA

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·     Corr btw c-Met and HGF mRNA expression.

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Vp

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·     C-Met mRNA not assoc w/ dz-free time or survival time

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·     C-Met expression assoc w/ mets fia lymphatics

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Expression of receptor activator of NF-KB ligand (RANKL) in neoplasia of dogs and cats

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·     Receptor activator of NFKB (RANK) , RANK-L and soluble decoy receptor osteoprotegerin (OPG) modulate osteoclastogenesis

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Jvim

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·     In health, RANKL-expressing bone stromal cells and osteoblasts activate osteoclasts through RANK ligation

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·     Dogs and cats- tumors involving bone and causing pain often express RANKL

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Survey of epithelial odontogenic tumors and cysts in dogs and cats

Back 252

·      

Hint 252

Vp

Front 253

IHC expression of p63 and ∆Np63 in mixed tumors of mammary glands and rel w/ p53 expression

Back 253

·     P63 expressed in myoepith cells of all benign mixed tumors and most mixed carcinomas

Hint 253

Vp

Back 254

·     No corr btw p63, p53 and ∆Np63 expression

Back 255

·     ↓p63 (and isoform ∆Np63) impt in dev of carcinomas in mixed tumors

Front 256

↑ expression of BRCA2 and RAD51 in LN mets of K9 mammary ACA

Back 256

·     Primary tumors vs mets - ↑ mRNA of BRCA1, BRCA2, and RAD51 in LN mets

Hint 256

Vp

Front 257

COX-2 expression in normal and neoplastic k9 mammary cell lines

Back 257

·     Some neoplastic k9 mammary cell lines over express COX-2

Hint 257

Vp

Back 258

·     COX-2 inhibition decreases PGE2 ­ production and cell proliferation

Front 259

Estrogen-dependent induction of COX-2 in canine prostate

Back 259

·     No COX-2 staining in prostate of untx or androgen-tx castrated or intact dogs

Hint 259

Vp

Back 260

·     Tx of dogs with estrogen resulted in squamous metaplasia with ^ COX-2 expression

Back 261

·     Indxn of COX-2 by estrogen

Front 262

Clonal origin and evolution of a transmissible tumor

Back 262

·     During progressive growth, CTVT down modulates MHC antigen expression

Hint 262

Cell

Back 263

·     CTVT only induced by transplanting living tumor cells

Front 264

IHC eval of GATA-4 in k9 testicular tumors

Back 264

·     Expressed in Sertoli cells, not germ cells

Hint 264

Vp

Back 265

·     Sertoli cell tumors –strong diffuse nuclear and weak cyto (+)

Back 266

·     Leydig cell tumors – strong nuclear, weak +/- cyto (+)

Back 267

·     Seminomas – (-)

Back 268

·     Mixed germ cell sex-cord stromal tumors – sex-cord stromal cells (+)

Back 269

·     GATA-4, -5, -6 expressed in ht, intestinal epith, gonads, and yolk sac endoderm

Back 270

·     GATA-1, -2, -3 hematopoietic cells (+)

Front 271

Bilat malig mixed mullerian tumor in A dog

Back 271

·     Intermingled carcinomatous and sarcomatous components

Hint 271

Vp

Back 272

·     Mets not mixed

Front 274

RAD51 prot expression ↑ in canine mammary CA

Back 274

·     RAD51 = key enzyme of homologous recombination and repair of DNA ds breaks

Hint 274

Vp0

Back 275

·     Expression reg by BRCA1 and BRCA2

Back 276

·     Mammary adenomas had ↓RAD51 mRNA when compared to non-neoplastic tissue in same dog

Front 277

Histo, IHC, and EM of vasculogenic mimicry in k9 mammary cancer

Back 277

·     K9 inflammatory mammwry cancer = most aggressive and lethal type

Hint 277

Vp0

Back 278

·     Gen of microvascular channels my malignant tumor cells (endoth-leke cells) w/o endoth cell participation ≡ vasculogenic mimicry

Back 279

·     Cells are AE1/ AE3 and CK14 (+), (-) to endoth markers

Back 280

·     Phenomenon more common in inflammatoryh vs non-infl mammary cancer (edema, erythema, firmness and warmth of glands)

Front 281

Px factors for dogs w/ mammary infl carcinoma

Back 281

·     If also have coagulopathy, ↓ survival time

Hint 281

Javma9

Back 282

·     Infl carcinoma = distinct entity, not part of tumor spectrum

Front 283

Prevalence and classification of spontaneous mammary intraepith lesions in dogs w/o clinical mammary dz

Back 283

·     Mammary intraepith lesions are noninvasive epith prolif that include ductal hyperplasia, atypical ductal hyperplasia, and ductal carcinoma in situ

Hint 283

Vp0

Back 284

·     Lo-grade DCIS had lower scores for all markers than did non-lesioned adj gland – PR sig ↓ in DCIS

Back 285

·     Many (most) tumors had loss of ERa

Front 286

Combined expression pattern of BMP2, LTBP4, and DERL-I discriminates malignant fm benign mammary tumors

Back 286

·      

Hint 286

Vp0

Back 287

·      

Front 288

Dysregulation of Wnt/b-catenin path in k9 cutaneous melanotic tumor

Back 288

·     Substantial ↑ in ctnnb1 (b-catenin) mRNA in melanotic tumors regardless of benign / malignant

Hint 288

Vp0

Back 289

·     b-catenin accumulation in cyto

Back 290

·     In melanoma, nuclear b-catenin

Back 291

·     Transformed melanocytes lose normal ctc w/ surrounding cells and prolif

Back 292

·     Benign in dobies, schnauzers // malig in poodles

Back 293

·     b-catenin implicated in neural tube formation – melanoblasts

Back 294

·     Dysreg of b-catenin path assoc w/ uncontrolled cell prolif and differentiation caused by accum of b-catenin in cells

Front 295

VEGF expression and microvasc density in soft tissue sarcomas in dogs

Back 295

·     VEGF participates in angiogenesis of soft tissue sarcomas

Hint 295

Jvdi0

Front 296

Novel carbohydrate tumor Ag C2-o-sLex is upreg in canine gastric CA

Back 296

·     Normal gastric mucosa is (-), >50% tumors (+)

Hint 296

Vp0

Back 297

·     More poorly differentiated tumor types had more and larger intensely stained areas

Back 298

·     Signet ring CA had markedly ↑ distribution and intensity of PAS and alcian blue staining than tubular CA

Front 299

Morphological study of canine LSA

Back 299

·     Presenting signs = generalized or local lymphadenopathy, extranodal dz involving skin and other sites

Hint 299

Vp0

Back 300

·     B-cell > T-cell> null cell (cd3 / cd79a-)

Back 301

·     Most B-cell cases = hi-grade centroblastic polymorphonuclear subtype

Back 302

·     Most T-cell = hi-grade pleomorphic mixed and large T-cell LSA subtypes

Back 303

·     Marginal zone LSA common // follicular LSA rare

Back 304

·     Overrepresentation of boxers for T-cell LSA

Back 305

·      

Front 306

Cardiac myxosarcoma w/ adrenal adenoma and pituitary hyperplasia resembling Carney complex in A dog

Back 306

·     Left atrial ossifying myxosarcoma, bilat adrenocort adenomas, mf pituitary hyperplasia w. expression of adrenocoricotropic hormone, and multiple Rathke’s cleft cysts

Hint 306

Vp0

Back 307

·     Cardiac myxoma is an endocardial neoplasm originating fm multipotent mesenchymal cells in subendocardial layer

Front 308

Urinary bladder mass in A dog

Back 308

·     Canine polypoid eosinophilic cystitis = benign inflammatory fibrous polyp

Hint 308

Vp0

Front 309

Adenomatous polyp w/ intestinal metaplasia of the esoph (Barrett Esoph) in A dog

Back 309

·     Papillary projections covered by columnar epith w/ goblet cells supported by fibrous stroma

Hint 309

Vp0