General Path Neoplasia

Front 1

explain the naming of benign tumors

Back 1

benign tumors are designated by attaching the suffix -oma to the cell type from which the tumor arises. A benign tumor arising in fibrous tissue is a fibroma; a benign cartilaginous tumor is a chondroma.

adenoma is applied to benign epithelial neoplasms producing gland patterns and to neoplasms derived from glands but not necessarily exhibiting gland patterns

Papillomas are benign epithelial neoplasms, growing on any surface, that produce microscopic or macroscopic finger-like fronds

Front 2

what is a glandular benign tumor?

Back 2

adenoma

Front 3

what is a polyp?

Back 3

A polyp is a mass that projects above a mucosal surface, as in the gut, to form a macroscopically visible structure

Front 4

explain nomenclature of malignant tumors

Back 4

Malignant neoplasms arising in mesenchymal tissue or its derivatives are called sarcomas. A cancer of fibrous tissue origin is a fibro sarcoma, and a malignant neoplasm composed of chondrocytes is a chondro sarcoma. Sarcomas are designated by their histogenesis (i.e., the cell type of which they are composed). Malignant neoplasms of epithelial cell origin are called carcinomas. It must be remembered that the epithelia of the body are derived from all three germ-cell layers; a malignant neoplasm arising in the renal tubular epithelium (mesoderm) is a carcinoma, as are the cancers arising in the skin (ectoderm) and lining epithelium of the gut (endoderm). It is evident that mesoderm may give rise to carcinomas (epithelial) and sarcomas (mesenchymal). Carcinomas may be qualified further. Carcinomas that grow in a glandular pattern are called adenocarcinomas, and those that produce squamous cells are called squamous cell carcinomas. Sometimes the tissue or organ of origin can be identified, as in the designation of renal cell adenocarcinoma or cholangiocarcinoma, which implies an origin from bile ducts. Sometimes the tumor shows little or no differentiation and must be called poorly differentiated or undifferentiated carcinoma.

Front 5

what is an epithelial cell malignant tumor?

Back 5

carcinoma

Front 6

what is a mesenchymal malignant tumor?

Back 6

sarcoma

Front 7

what is a tumor that has all three germ layers in it?

Back 7

teratoma

Front 8

what is an adenocarcinoma?

Back 8

malignant glandular like epithelial tumor

Front 9

what is anaplasia?

Back 9

The term anaplasia literally means "to form backward". It implies dedifferentiation, or loss of structural and functional differentiation of normal cells.

the more rapidly growing and the more anaplastic a tumor, the less likely it is to have specialized functional activity.

Front 10

describe histologic characteristics anaplasia

Back 10

Anaplastic cells display marked pleomorphism (i.e., marked variation in size and shape) (Fig. 6-4). Characteristically the nuclei are extremely hyperchromatic (darkly stained) and large. The nuclear-to-cytoplasmic ratio may approach 1:1 instead of the normal 1:4 or 1:6. Giant cells that are considerably larger than their neighbors may be formed and possess either one enormous nucleus or several nuclei. Anaplastic nuclei are variable and bizarre in size and shape. The chromatin is coarse and clumped, and nucleoli may be of astounding size. More important, mitoses are often numerous and distinctly atypical; anarchic multiple spindles may be seen and sometimes appear as tripolar or quadripolar forms (Fig. 6-5). Also, anaplastic cells usually fail to develop recognizable patterns of orientation to one another (i.e., they lose normal polarity). They may grow in sheets, with total loss of communal structures, such as gland formations or stratified squamous architecture. Anaplasia is the most extreme disturbance in cell growth encountered in the spectrum of cellular proliferations.

Front 11

describe histologic appearance dysplasia

Back 11

dysplasia, a term used to describe disorderly but non-neoplastic proliferation. Dysplasia is encountered principally in the epithelia. It is a loss in the uniformity of individual cells and in their architectural orientation. Dysplastic cells exhibit considerable pleomorphism and often possess hyperchromatic nuclei that are abnormally large for the size of the cell. Mitotic figures are more abundant than usual. Frequently the mitoses appear in abnormal locations within the epithelium. In dysplastic stratified squamous epithelium, mitoses are not confined to the basal layers, where they normally occur, but may appear at all levels and even in surface cells. There is considerable architectural anarchy.

Front 12

What is the difference between dysplasia and anaplasia?

Back 12

Dysplasia leads to the development of neoplasia. Anaplasia is characteristic of malignant neoplasia.

Also, anaplasia I think has more messed up differentiation

Front 13

explain differences in rate of growth of tumors

Back 13

The rate of growth of malignant tumors correlates in general with their level of differentiation. In other words, rapidly growing tumors tend to be poorly differentiated. However, there is wide variation in the rate of growth.

Front 14

explain how benign neoplasms don't invade

Back 14

they usually develop a capsule either from host tissue, or from self. (sometimes they don't have a capsule tho)

They don't invade host tissue. It does not have the capacity to infiltrate, invade, or metastasize to distant sites, as do malignant neoplasms

Front 15

explain local invasiveness of malignant tumors

Back 15

Cancers grow by progressive infiltration, invasion, destruction, and penetration of the surrounding tissue (Figs. 6-9 and 6-10). They do not develop well-defined capsules. There are, however, occasional instances in which a slowly growing malignant tumor deceptively appears to be encased by the stroma of the surrounding host tissue, but microscopic examination usually reveals tiny crablike feet penetrating the margin and infiltrating adjacent structures. The infiltrative mode of growth makes it necessary to remove a wide margin of surrounding normal tissue when surgical excision of a malignant tumor is attempted. Surgical pathologists carefully examine the margins of resected tumors to ensure that they are devoid of cancer cells (clean margins). Next to the development of metastases, local invasiveness is the most reliable feature that distinguishes malignant from benign tumors.

Front 16

how do malignant tumors disseminate?

Back 16

Malignant neoplasms disseminate by one of three pathways: (1) seeding within body cavities, (2) lymphatic spread, or (3) hematogenous spread.

Front 17

what are most common metastatic sites for hematogenous dissemination?

Back 17

Since all portal area drainage flows to the liver, and all caval blood flows to the lungs, the liver and lungs are the most frequently involved secondary sites in hematogenous dissemination.

Front 18

what are principal causes of carcinogenesis?

Back 18

Genetic damage

Four classes of normal regulatory genes—growth-promoting proto-oncogenes, growth-inhibiting tumor suppressor genes, genes that regulate programmed cell death (i.e., apoptosis), and genes involved in DNA repair—are the principal targets of genetic damage.

Front 19

how many copies of a gene must be damaged for carcinogenesis to occur?

Back 19

Mutant alleles of proto-oncogenes are called oncogenes. They are considered dominant because mutation of a single allele can lead to cellular transformation. In contrast, typically both normal alleles of tumor suppressor genes must be damaged for transformation to occur, so this family of genes is sometimes referred to as recessive oncogenes.

Front 20

what types of cells will be in a tumor? will they be monoclonal?

Back 20

Even though most malignant tumors are monoclonal in origin, by the time they become clinically evident, their constituent cells are extremely heterogeneous. During progression, tumor cells are subjected to immune and nonimmune selection pressures. For example, cells that are highly antigenic are destroyed by host defenses, whereas those with reduced growth factor requirements are positively selected. A growing tumor, therefore, tends to be enriched for subclones that “beat the odds” and are adept at survival, growth, invasion, and metastasis.

Front 21

what are the fundamental changes in cancer (in terms of cell physiology)?

Back 21

1. Self-sufficiency in growth signals
2. Insensitivity to growth-inhibitory signals
3. Evasion of apoptosis
4. Limitless replicative potential (i.e., overcoming cellular senescence and avoiding mitotic catastrophe)
5. Development of sustained angiogenesis
6. Ability to invade and metastasize
7. Genomic instability resulting from defects in DNA repair

Front 22

explain oncogenes

Back 22

Genes that promote autonomous cell growth in cancer cells are called oncogenes. They are derived by mutations in proto-oncogenes and are characterized by the ability to promote cell growth in the absence of normal growth-promoting signals. Their products, called oncoproteins, resemble the normal products of proto-oncogenes except that oncoproteins are devoid of important regulatory elements, and their production in the transformed cells does not depend on growth factors or other external signals

Front 23

explain growth factors and cancer

Back 23

All normal cells require stimulation by growth factors to undergo proliferation. Most soluble growth factors are made by one cell type and act on a neighboring cell to stimulate proliferation (paracrine action). Many cancer cells acquire growth self-sufficiency, however, by acquiring the ability to synthesize the same growth factors to which they are responsive.

overexpression of growth factor receptors, which can render cancer cells hyper-responsive to levels of the growth factor that would not normally trigger proliferation

Front 24

explain signal transduction proteins in cancer

Back 24

A relatively common mechanism by which cancer cells acquire growth autonomy is mutations in genes that encode various components of the signaling pathways downstream of growth factor receptors. These signaling molecules couple growth factor receptors to their nuclear targets. Many such signaling proteins are associated with the inner leaflet of the plasma membrane, where they receive signals from activated growth factor receptors and transmit them to the nucleus, either through second messengers or through a cascade of phosphorylation and activation of signal transduction molecules. Two important members in this category are RAS and ABL.

Front 25

explain RAS

Back 25

RAS is most commonly mutated proto-oncogene in human cancer.

When a normal cell is stimulated through a growth factor receptor, inactive (GDP-bound) RAS is activated to a GTP-bound state. Activated RAS recruits RAF-1 and stimulates the MAP-kinase pathway to transmit growth-promoting signals to the nucleus. MYC gene is one of several targets of the activated RAS pathway. The mutant RAS protein is permanently activated because of inability to hydrolyze GTP, leading to continuous stimulation of cells without any external trigger. The anchoring of RAS to the cell membrane by the farnesyl moiety is essential for its action, and drugs that inhibit farnesylation can inhibit RAS action.

Front 26

explain MYC

Back 26

A host of oncoproteins, including products of the MYC, MYB, JUN, FOS, and REL oncogenes, function as transcription factors that regulate the expression of growth-promoting genes, such as cyclins. Of these, the MYC gene is involved most commonly in human tumors. The MYC proto-oncogene is expressed in virtually all cells, and the MYC protein is induced rapidly when quiescent cells receive a signal to divide. In normal cells, MYC levels decline to near basal level when the cell cycle begins. In contrast, oncogenic versions of the MYC gene are associated with persistent expression or overexpression, contributing to sustained proliferation.

MYC promotes tumorigenesis by increasing expression of genes that promote progression through the cell cycle and repressing genes that slow or prevent progression through the cell cycle. Dysregulation of the MYC gene resulting from a t(8;14) translocation occurs in Burkitt lymphoma, a B-cell tumor.

Front 27

explain cyclins/CDKs in cancer

Back 27

Complexes of cyclins with cyclin-dependent kinases (CDKs) drive the cell cycle by phosphorylating various substrates; CDKs are controlled by inhibitors; mutations in genes encoding cyclins, CDKs, and CDK inhibitors result in uncontrolled cell cycle progression. Such mutations are found in wide variety of cancers including melanomas, brain, lung, and pancreatic cancer.

cyclin D/CDK4 are the most common problems with this

Front 28

explain RBs

how many hits do you need?

Back 28

RB is a tumor suppressor

you need two hits (because have two copies) to get cancer from this

in inherited/familial disease, inherit one hit, and need the other hit to be a mutation

in sporadic disease, need both mutations to occur spontaneously

RB enforces G1 gap (between M and S)

It binds E2F and prevents it from working as a TF

The initiation of DNA replication requires the activity of cyclin E/CDK2 complexes, and expression of cyclin E is dependent on the E2F family of transcription factors. Early in G1, RB is in its hypophosphorylated active form, and it binds to and inhibits the E2F family of transcription factors, preventing transcription of cyclin E. Hypophosphorylated RB blocks E2F-mediated transcription in at least two ways (Fig. 6-21). First, it sequesters E2F, preventing it from interacting with other transcriptional activators. Second, RB recruits chromatin remodeling proteins, such as histone deacetylases and histone methyltransferases, which bind to the promoters of E2F-responsive genes such as cyclin E. These enzymes modify chromatin at the promoters to make DNA insensitive to transcription factors. This situation is changed upon mitogenic signaling. Growth factor signaling leads to cyclin D expression and activation of cyclin D–CDK4/6 complexes. These complexes phosphorylate RB, inactivating the protein and releasing E2F to induce target genes such as cyclin E. Expression of cyclin E then stimulates DNA replication and progression through the cell cycle. When the cells enter S phase, they are committed to divide without additional growth factor stimulation. During the ensuing M phase, the phosphate groups are removed from RB by cellular phosphatases, regenerating the hypophosphorylated form of RB.

Front 29

how do viruses get around RB?

Back 29

HPV makes E7, which binds RB and makes it non-functional. That's how you get hpv related cancer.

Front 30

explain p53

Back 30

this is a tumor suppressor. called guardian of the genome for a reason.

In nonstressed, healthy cells, p53 has a short half-life (20 minutes) because of its association with MDM2, a protein that targets it for destruction. When the cell is stressed, for example by an assault on its DNA, p53 undergoes post-transcriptional modifications that release it from MDM2 and increase its half-life. During the process of being unshackled from MDM2, p53 also becomes activated as a transcription factor. Dozens of genes whose transcription is triggered by p53 have been found. They can be grouped into two broad categories: those that cause cell cycle arrest and those that cause apoptosis. If DNA damage can be repaired during cell cycle arrest, the cell reverts to a normal state; if the repair fails, p53 induces apoptosis or senescence.

Of human tumors, 70% have homozygous loss of p53. Patients with the rare Li-Fraumeni syndrome inherit one defective copy in the germ line and lose the second one in somatic tissues; such individuals develop a variety of tumors.
• As with RB, p53 can be incapacitated by binding to proteins encoded by oncogenic DNA viruses like HPV, and possibly EBV and HBV.

Front 31

explain TGF-B and APC in cancer. Why are these grouped together? What proteins do they work with?

Back 31

Transforming Growth Factor-β and Adenomatous Polyposis Coli–β-Catenin Pathways
• TGF-β inhibits proliferation of many cell types by activation of growth-inhibiting genes like CDKIs and suppression of growth-promoting genes like MYC and cyclins.
• TGF-β function is compromised in many tumors by mutations in its receptors (colon, stomach, endometrium) or by mutational inactivation of SMAD genes that transduce TGF-β signaling (pancreas).
• APC gene exerts antiproliferative actions by regulating the destruction of the cytoplasmic protein β-catenin. With a loss of APC, β-catenin is not destroyed and it translocates to the nucleus, where it acts as a growth-promoting transcription factor.
• In familial adenomatous polyposis syndrome inheritance of a germ-line mutation in the APC gene causes the development of hundreds of colonic polyps at a young age. One or more of these polyps evolves into a colonic cancer with loss of heterozygosity at the APC locus. Somatic loss of both alleles of the of APC gene is seen in approximately 70% of sporadic colon cancers.

Front 32

explain evasion of apoptosis in cancer

Back 32

• Apoptosis can be initiated through the extrinsic or intrinsic pathways.
• Both pathways result in the activation of a proteolytic cascade of caspases that destroys the cell.
• Mitochondrial outer membrane permeabilization is regulated by the balance between pro-apoptotic (e.g., BAX, BAK) and anti-apoptotic molecules (BCL2, BCL-XL). BH-3-only molecules activate apoptosis by tilting the balance in favor of the pro-apoptotic molecules.
• In 85% of follicular B-cell lymphomas the anti-apoptotic gene BCL2 is activated by the t(8;14) translocation.

Front 33

explain telomerase in cancer

Back 33

Limitless Replicative Potential
• In normal cells, which lack expression of telomerase, the shortened telomeres generated by cell division eventually activate cell cycle checkpoints, leading to senescence and placing a limit on the number of divisions a cell may undergo.
• In cells that have disabled checkpoints, DNA repair pathways are inappropriately activated by shortened telomeres, leading to massive chromosomal instability and mitotic crisis.
• Tumor cells reactivate telomerase, thus staving off mitotic catastrophe and achieving immortality.

Front 34

explain angiogenesis in cancer

Back 34

The angiogenic switch is controlled by several physiologic stimuli, such as hypoxia. Relative lack of oxygen stimulates production of a variety of pro-angiogenic cytokines, such as vascular endothelial growth factor (VEGF), through activation of hypoxia-induced factor-1α (HIF1α), an oxygen-sensitive transcription factor. HIF1α is continuously produced, but in normoxic settings the von Hippel–Lindau protein (VHL) binds to HIF1α, leading to ubiquitination and destruction of HIF1α. In hypoxic conditions, such as a tumor that has reached a critical size, the lack of oxygen prevents HIF1α recognition by VHL, and it is not destroyed. HIF1α translocates to the nucleus and activates transcription of its target genes, such as VEGF. Because of these activities, VHL acts as a tumor suppressor gene, and germ-line mutations of the VHL gene are associated with hereditary renal cell cancers, pheochromocytomas, hemangiomas of the central nervous system, retinal angiomas, and renal cysts (VHL syndrome).

Many other factors regulate angiogenesis; for example, p53 induces synthesis of the angiogenesis inhibitor thrombospondin-1.

Front 35

explain invasion and metastasis

Back 35

Invasion and Metastasis
• Ability to invade tissues, a hallmark of malignancy, occurs in four steps: loosening of cell-cell contacts, degradation of ECM, attachment to novel ECM components, and migration of tumor cells.
• Cell-cell contacts are lost by the inactivation of E-cadherin through a variety of pathways.
• Basement membranes and interstitial matrix degradation is mediated by proteolytic enzymes secreted by tumor cells and stromal cells, such as MMPs and cathepsins.
• Proteolytic enzymes also release growth factors sequestered in the ECM and generate chemotactic and angiogenic fragments from cleavage of ECM glycoproteins.
• The metastatic site of many tumors can be predicted by the location of the primary tumor. Many tumors arrest in the first capillary bed they encounter (lung and liver, most commonly).
• Some tumors show organ tropism, probably due to expression of adhesion or chemokine receptors whose ligands are expressed by the metastatic site.

Front 36

explain HNPCC

Back 36

Patients with HNPCC syndrome have defects in the mismatch repair system and develop carcinomas of the colon. These patients show microsatellite instability (MSI), in which short repeats throughout the genome change in length.

Front 37

explain xeroderma pigmentosum

Back 37

Patients with xeroderma pigmentosum have a defect in the nucleotide excision repair pathway and are at increased risk for the development of cancers of the skin exposed to UV light, because of an inability to repair pyrimidine dimers.

Front 38

what are direct acting carcinogens?

Back 38

Direct-acting agents require no metabolic conversion to become carcinogenic.

an example is chemotherapy CAUSING leukemia

Front 39

what are indirect-acting carcinogens?

Back 39

The designation indirect-acting agent refers to chemicals that require metabolic conversion to an ultimate carcinogen before they become active. Some of the most potent indirect chemical carcinogens—the polycyclic hydrocarbons—are present in fossil fuels. For example, benzo [a] pyrene and other carcinogens are formed in the high-temperature combustion of tobacco in cigarette smoking. These products are implicated in the causation of lung cancer in cigarette smokers.

Front 40

how do chemical carcinogens work?

Back 40

Because malignant transformation results from mutations, it should come as no surprise that most chemical carcinogens are mutagenic. Indeed, all direct and ultimate carcinogens contain highly reactive electrophile groups that form chemical adducts with DNA, as well as with proteins and RNA. Although any gene may be the target of chemical carcinogens, the commonly mutated oncogenes and tumor suppressors, such as RAS and p53, are important targets of chemical carcinogens.

Front 41

explain radiation carcinogenesis

Back 41

• Ionizing radiation causes chromosome breakage, translocations, and, less frequently, point mutations, leading to genetic damage and carcinogenesis.
• UV rays induce the formation of pyrimidine dimers within DNA, leading to mutations. Therefore UV rays can give rise to squamous cell carcinomas and melanomas of the skin.

UV light has several biologic effects on cells. Of particular relevance to carcinogenesis is the ability to damage DNA by forming pyrimidine dimers. This type of DNA damage is repaired by the nucleotide excision repair pathway. With extensive exposure to UV light, the repair systems may be overwhelmed, and skin cancer results. As mentioned above, patients with the inherited disease xeroderma pigmentosum have a defect in the nucleo-tide excision repair pathway. As expected, there is a greatly increased predisposition to skin cancers in this disorder.

Front 42

most common causes of cancer in men

Back 42

Prostate, lung, colorectal

Front 43

most common causes of cancer death among men

Back 43

lung, prostate, colorectal

(the first two switch for just most common causes of cancer in men)

Front 44

most common causes of cancer in women

Back 44

breast, lung, colorectal

Front 45

most common causes of cancer death in women

Back 45

lung, breast, colorectal

Front 46

explain HTLV-1

Back 46

oncogenic RNA (retrovirus) virus

• HTLV-1 causes a T-cell leukemia that is endemic in Japan and the Caribbean.
• HTLV-1 encodes a viral TAX protein, which turns on genes for cytokines and their receptors in infected T cells. This sets up autocrine and paracrine signaling loops that stimulate T-cell proliferation. Although this proliferation is initially polyclonal, the proliferating T cells are at increased risk of secondary mutations that lead to the outgrowth of a monoclonal leukemia.

Front 47

what does HPV E6 do?

Back 47

binds to and mediates the degradation of p53 and BAX, a pro-apoptotic member of the BCL2 family, and it activates telomerase.

Front 48

H. pylori and cancer

Back 48

• H. pylori infection has been implicated in both gastric adenocarcinoma and MALT lymphoma.
• The mechanism of H. pylori –induced gastric cancers is multifactorial, including immunologically mediated chronic inflammation, stimulation of gastric cell proliferation, and production of reactive oxygen species that damage DNA. H. pylori pathogenicity genes, such as CagA, may also contribute by stimulating growth factor pathways.
• It is thought that H. pylori infection leads to polyclonal B-cell proliferations and that eventually a monoclonal B-cell tumor (MALT lymphoma) emerges as a result of accumulation of mutations.

Front 49

HBV/HCV and cancer

Back 49

• Between 70% and 85% of hepatocellular carcinomas worldwide are due to infection with HBV or HCV.
• The oncogenic effects of HBV and HCV are multifactorial, but the dominant effect seems to be immunologically mediated chronic inflammation, hepatocellular injury, stimulation of hepatocyte proliferation, and production of reactive oxygen species that can damage DNA.
• The HBx protein of HBV and the HCV core protein can activate a variety of signal transduction pathways that may also contribute to carcinogenesis.

Front 50

what is cancer cachexia?

Back 50

Cachexia, defined by progressive loss of body fat and lean body mass, accompanied by profound weakness, anorexia, and anemia, is caused by release of cytokines by the tumor or host.

TNFa from macrophages thought responsible.

Front 51

what are paraneoplastic syndromes?

Back 51

Paraneoplastic syndromes, defined by systemic symptoms that cannot be explained by tumor spread or by hormones appropriate to the tissue, are caused by the ectopic production and secretion of bioactive substances, such as ACTH (cushing's), PTHrP (hypercalcemia), or TGF-α (hypercalcemia).

The paraneoplastic syndromes are diverse and are associated with many different tumors (Table 6-5). The most common syndromes are hypercalcemia, Cushing syndrome, and nonbacterial thrombotic endocarditis

Front 52

explain cancer grading

Back 52

The grading of a cancer attempts to establish some estimate of its aggressiveness or level of malignancy based on the cytologic differentiation of tumor cells and the number of mitoses within the tumor. The cancer may be classified as grade I, II, III, or IV, in order of increasing anaplasia.

Front 53

explain staging of cancer

Back 53

Staging of cancers is based on the size of the primary lesion, its extent of spread to regional lymph nodes, and the presence or absence of metastases. This assessment is usually based on clinical and radiographic examination (computed tomography and magnetic resonance imaging) and in some cases surgical exploration. Two methods of staging are currently in use: the TNM system (T, primary tumor; N, regional lymph node involvement; M, metastases) and the AJC (American Joint Committee) system. In the TNM system, T1, T2, T3, and T4 describe the increasing size of the primary lesion; N0, N1, N2, and N3 indicate progressively advancing node involvement; and M0 and M1 reflect the absence or presence of distant metastases. In the AJC method, the cancers are divided into stages 0 to IV, incorporating the size of primary lesions and the presence of nodal spread and of distant metastases. Examples of the application of these two staging systems are cited in subsequent chapters. It is worth noting that when compared with grading, staging has proved to be of greater clinical value.

Front 54

explain TNM staging system

Back 54

T = size of tumor (1-3)
N = amount of lymph node involvement (0-4)
M = presence of metastases (0 or 1)

Front 55

explain what PSA is and problem with it

Back 55

Prostatic carcinoma can be suspected when elevated levels of PSA are found in the blood. However, PSA screening also highlights problems encountered by virtually every tumor marker. Although PSA levels are often elevated in cancer, PSA levels also may be elevated in benign prostatic hyperplasia (Chapter 18). Furthermore, there is no PSA level that ensures that a patient does not have prostate cancer. Thus, the PSA test suffers from both low sensitivity and low specificity.

Front 56

explain molecular methods in cancer diagnosis/staging

Back 56

• Molecular analyses are used to determine diagnosis, prognosis, the detection of minimal residual disease (eg PCR to find BCR-ABL in chronic myeloid leukemia), and the diagnosis of hereditary predisposition to cancer.
• Molecular profiling of tumors by cDNA arrays (micro-array) can determine expression of large segments of the genome at once and can be useful in molecular stratification of otherwise identical tumors for the purpose of treatment and prognostication.