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205 Cards in this Set
- Front
- Back
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2ND LEADING CAUSE OF DEATH IN THE UNITED STATES
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CANCER
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% OF AMERICANS NOW LIVING WHO WILL GET CANCER IN THEIR LIFETIME
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30%
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MOST FEARED DISEASES (GALLUP POLL)
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CANCER - 58%
BLINDNESS - 21% HEART DISEASE - 10% ALZEIMER’S DISEASE - 4% STROKE - 2% LOSS OF LIMB - 2% ARTHRITIS - 1% |
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US CANCER DIAGNOSES 2010
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ALABAMA – 25,530
ARKANSAS – 16,070 FLORIDA – 113,400 GEORGIA – 44,580 MISSISSIPPI – 14,900 TEXAS – 105,000 |
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US CANCER DEATHS 2010
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ALABAMA – 10,210
ARKANSAS – 6,460 FLORIDA – 40,980 GEORGIA – 15,860 MISSISSIPPI – 6.060 TEXAS – 36,770 |
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NEOPLASM
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UNCORDINATED “NEW GROWTH” OF TISSUE
UNLIMITED GROWTH POTENTIAL DOES NOT REGRESS WITH REMOVAL OF INITIATING STIMULIS |
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NEOPLASIA INVOLVES
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GENETIC CHANGES THAT ALLOW EXCESSIVE AND UNREGULATED CELL PROLIFERATION THAT ARE INDEPENDENT OF PHYSIOLOGIC GROWTH-REGULATORY MECHANISMS
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NEOPLASIA LIMITATIONS
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NUTRITIONAL SUPPORT
VASCULAR SUPPLY SOMETIMES ENDOCRINE SUPPORT |
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TUMOR
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LITERALLY: A SWELLING
(MAY OR MAY NOT BE A NEOPLASM) (TO ME: NEOPLASM = TUMOR) |
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ONCOLOGY
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THE STUDY OF NEOPLASMS
ONCOLOGIC SURGEONS RADIOLOGIC ONCOLOGISTS MEDICAL ONCOLOGISTS PATHOLOGISTS |
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NEOPLASMS -CLASSIFICATION-
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NAME SHOULD TELL: CELL OF ORIGIN, LIKELY BEHAVIOR
EXCEPTIONS = FOLLOW RULES MOST END IN -OMA |
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TYPES OF NEOPLASMS
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BENIGN
MALIGNANT (CANCER) |
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BENIGN
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A LOCALLY GROWING NEOPLASM WHICH USUALLY DOES NOT KILL THE PATIENT
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MALIGNANT
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(CANCER)
AN INVASIVE NEOPLASM WHICH HAS THE CAPACITY TO SPREAD TO OTHER PARTS OF THE BODY AND WILL KILL THE HOST UNLESS REMOVED |
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BENIGN NEOPLASM
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BENIGN = “BLESSED”
REMAIN LOCALIZED CANNOT SPREAD TO OTHER SITES CAN BE SURGICALLY REMOVED PATIENT GENERALLY SURVIVES CAN BE SERIOUS (SIZE, LOCATION, FUNCTION) DESIGNATED BY “-OMA” |
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USUALLY BENIGN TUMORS ARE NAMED BY
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ADDING -OMA TO THE TISSUE OF HISTOGENESIS
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BENIGN NEOPLASMS
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FIBROMA – FIBROUS CT
CHONDROMA – CARTILAGE OSTEOMA – BONE LIPOMA – ADIPOSE TISSUE… ADENOMA – GLANDULAR TISSUE PAPILLOMA - EPITHELIAL |
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MALIGNANT NEOPLASM
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MALIGNANT = “MALICIOUS”
AKA CANCER (“CRAB”) INVADES AND DESTROYS ADJACENT TISSUE CAN SPREAD (METASTASIZE) TO DISTANT SITES MAY KILL THE HOST TWO TYPES: CARCINOMAS, SARCOMAS |
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CARCINOMA
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A MALIGNANT NEOPLASM DERIVED FROM EPITHELIAL TISSUES
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CARCINOMAS GENERAL
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EPITHELIAL ORIGIN
90% OF MALIGNANCIES OLDER ADULTS ULCERATED MASSES FAIR PROGNOSIS |
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CARCINOMA EXAMPLES
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SQUAMOUS CELL CARCINOMA: STRATIFIED SQUAMOUS EPITHELIUM
ADENOCARCINOMA: GLANDULAR EPITHELIUM TRANSITIONAL CELL CARCINOMA: TRANSITIONAL EPITHELIUM |
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SARCOMA
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A MALIGNANT NEOPLASM DERIVED FROM MESENCHYMAL TISSUE
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SARCOMAS GENERAL
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MESENCHYMAL ORIGIN
10% OF MALIGNANCIES YOUNGER PATIENTS BULKY, FLESHY MASSES POORER PROGNOSIS |
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SARCOMA EXAMPLES
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FIBROSARCOMA
CHONDROSARCOMA OSTEOSARCOMA LIPOSARCOMA RHABDOMYOSARCOMA LEUKEMIA LYMPHOMA |
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NEOPLASM -COMPONENTS-
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PARENCHYMA
STROMA |
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NEOPLASM PARENCHYMA
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NEOPLASTIC COMPONENT
CELLS SOMEWHAT RESEMBLE EACH OTHER DETERMINES BIOLOGIC BEHAVIOR DETERMINES NOMENCLATURE |
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NEOPLASM STROMA
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SUPPORTING TISSUES
CONNECTIVE TISSUE, BLOOD VESSELS CRUCIAL FOR TUMOR SURVIVAL IMPARTS PHYSICAL CONSISTENCY TO TUMOR MAY INFLUENCE NOMENCLATURE (DESMOPLASIA = ABUNDANT FIBROUS TISSUE; SCIRRHOUS CARCINOMA OF BREAST) |
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NEOPLASMS -CLASSIFICATION EXCEPTIONS-
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SOME NAMED AFTER A PERSON (EWING’S SARCOMA)
SOME NAMES RETAINED BY USAGE (LEUKEMIA) SOME HAVE DESCRIPTIVE NAMES (PAPILLARY CYSTADENOMA LYMPHOMATSUM) SOME HAVE MULTIPLE NAMES (RENAL CELL CA, GRAWITZ TUMOR, HYPERNEPHROMA) MIXED TUMORS EXIST (DIVERGENT DIFFERENTIATION, MULTIPLE CELL TYPES, PLEOMORPHIC ADENOMA OF SALIVARY GLAND, FIBROADENOMA OF BREAST) |
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CHORISTOMA
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SINGLE ADULT TISSUE IN AN ECTOPIC LOCATION
DEVELOPMENTAL NEOPLASM |
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HAMARTOMA
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ONE OR MORE TISSUES IN A NORMAL LOCATION IN EXCESSIVE AMOUNT
DEVELOPMENTAL NEOPLASM |
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TERATOMA
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SEVERAL TISSUE IN ECTOPIC LOCATION
DEVELOPMENTAL NEOPLASM |
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BENIGN vs MALIGNANT
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DIFFERENTIATION
MODE OF GROWTH RATE OF GROWTH METASTASIS |
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DIFFERENTIATION IS
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THE EXTENT TO WHICH TUMOR CELLS RESEMBLE NORMAL CELLS
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BENIGN NEOPLASMS ARE COMPOSED OF CELLS WHICH
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CLOSELY RESEMBLE NORMAL CELLS
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MALIGNANT NEOPLASMS VARY IN
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DIFFERENTIATION BUT ARE LESS DIFFERENTIATED THAN NORMAL CELLS
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DEGREES OF DIFFERENTIATION
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WELL DIFFERENTIATED (CLOSE TO NORMAL; RECOGNIZABLE BUT ABNORMAL)
MODERATELY DIFFERENTIATED (FAIRLY ABNORMAL) POORLY DIFFERENTIATED (VERY ABNORMAL; MAY NOT BE RECOGNIZABLE) |
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NEOPLASM FUNCTIONAL CAPACITIES
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BETTER DIFFERENTIATED TUMORS RETAIN FUNCTIONAL CAPABILITIES
PRODUCTION OF CELL PRODUCTS (SQUAMOUS CELL CARCINOMAS MAKE KERATIN; ADENOCARCINOMA MAKE MUCIN) ELABORATION OF HORMONES |
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NEOPLASM HORMONE PRODUCTION
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NEUROENDOCRINE TUMORS
ECTOPIC HORMONE PRODUCTION PARANEOPLASTIC SYNDROMES LUNG CANCERS… ACTH, PTH MAY MISLEAD DIAGNOSIS |
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NEOPLASM FETAL PROTEINS
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LIVER AND COLON CANCERS
CARCINOEMBRYONIC ANTIGEN… α-FETOPROTEIN… USED DIAGNOSTICALLY USED PROGNOSTICALLY |
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POORLY DIFFERENTIATED TUMORS
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GROW FASTER
ARE MORE INVASIVE ARE MORE LIKELY TO METASTASIZE METASTASIZE EARLIER EXHIBIT LESS FUNCTIONAL CAPACITY HAVE A POORER PROGNOSIS BUT ARE MORE SENSITIVE TO IRRADIATION AND CHEMOTHERAPY |
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BENIGN VS MALIGNANT -HISTOLOGIC DIFFERENTIATION-
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BENIGN: WELL
MALIGNANT: POORLY |
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DYSPLASIA DEFINITION
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(ATYPIA)
LOSS OF UNIFORMITYOF CELLS AND THEIR ARCHITECTURAL ORIENTATION WITHIN TISSUE DISORDERLY BUT TECHNICALLY NON-NEOPLASTIC PROLIFERATION |
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DYSPLASIA CHARACTERISTICS
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OFTEN “PRE-MALIGNANT”: MAY BE MERELY REACTIVE; MAY OR MAY NOT PROGRESS TO CANCER; ODDS OF PROGRESSION INCREASES WITH SEVERITY OF CHANGES
APPLIES BEST TO EPITHELIUM |
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DYSPLASIA -HISTOLOGIC CRITERIA-
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INCREASED NUCLEAR:CYTOPLASMIC RATIO
INCREASED HYPERCHROMATISM INCREASED MITOTIC INDEX MITOTIC FIGURES IN ABNORMAL LOCATIONS NUCLEAR AND CYTOPLASMIC PLEOMORPHISM ARCHITECTURAL ANARCHY (JUMBLING OF CELL LAYERS) INTACT BASEMENT MEMBRANE (NO INVASION) |
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DYSPLASIA -DEGREES-
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NO DYSPLASIA
MILD DYSPLASIA (CHANGES RESTRICTED TO BASAL CELL LAYER) MODERATE DYSPLASIA (DYSPLASIA IN LOWER HALF OF EPITHELIUM) SEVERE DYSPLASIA (DYSPLASIA IN UPPER EPITHELIAL LEVELS) CARCINOMA-IN-SITU (FULL THICKNESS INVOLVEMENT) |
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ANAPLASIA
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LACK OF CELLULAR DIFFERENTIATION
REALLY BAD DYSPLASIA CELLS APPEAR PRIMATIVE, UNDIFFERENTIATED AND UNSPECIALIZED HALLMARK OF MALIGNANCY! |
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ANAPLASIA MAY RESULT FROM
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DEDIFFERENTIATION OF CELLS
OR LACK OF STEM CELL DIFFERENTIATION |
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ANAPLASIA HISTOLOGIC CRITERIA
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SAME AS DYSPLASIA BUT MORE SEVERE
FORMATION OF TUMOR GIANT CELLS ATYPICAL MITOTIC FIGURES (TRIPOLAR) |
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BENIGN VS MALIGNANT -MODE OF GROWTH-
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BENIGN: EXPANSILE
MALIGNANT: INVASIVE RELIABLE FEATURE FOR BENIGN vs. MALIGNANT |
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BENIGN TUMORS MODE OF GROWTH
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EXPANSILE
DISPLACE AND COMPRESS SHARPLY DEMARCATED MAY HAVE A FIBROUS CAPSULE |
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MALIGNANT TUMORS MODE OF GROWTH
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INVASIVE
INFILTRATE, PENETRATE, DESTROY… CANCER = “CRAB” |
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DYSPLASIA (ANAPLASIA) + INVASION =
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CANCER
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BENIGN VS MALIGNANT -RATE OF GROWTH-
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BENIGN: SLOW
MALIGNANT: FAST |
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BENIGN TUMORS RATE OF GROWTH
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TYPICALLY GROW SLOWLY
MAY ACHIEVE LARGE SIZES MAY GROW RAPID DUE TO HORMONAL STIMULATION |
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MALIGNANT TUMORS RATE OF GROWTH
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USUALLY GROW RAPIDLY
CORRELATES WITH DIFFERENTIATION STILL TAKES YEARS TO BECOME A CLINICAL TUMOR MAY OUTGROW BLOOD SUPPLY & NECROSE |
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METASTASIS
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THE ABILITY TO SEED REMOTE TISSUES BY MALIGNANT CELLS
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BENIGN VS MALIGNANT -METASTASIS-
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BENIGN: NOT CAPABLE
MALIGNANT: CAPABLE |
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PRIMARY TUMOR
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AT SITE OF ORIGIN
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SECONDARY TUMORS
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METASTASES
AT SITES OF SEEDING |
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METASTASIS
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ALL MALIGNANT NEOPLASMS HAVE THE CAPACITY TO METASTASIZE
SOME ARE MORE PRONE THAN OTHERS (BASAL CELL CA OF SKIN RARELY METASTASIZES; PRIMARY BRAIN TUMORS RARELY METASTASIZE; SMALL CELL CARCINOMA OF LUNG ALMOST METASTASIZES) METASTASIS MAY BE THE FIRST SIGN (EMBRYONAL CARCINOMA OF TESTIS) 50% HAVE METASTASES AT DIAGNOSIS (30% CLINICALLY EVIDENT; ADDITIONAL 20% OCCULT) MORE RELIABLE FEATURE FOR BENIGN vs MALIGNANT SIGNIFICANT FACTOR IN PROGNOSIS |
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METASTASIS FACTORS
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TYPE OF CANCER
DEGREE OF ANAPLASIA TUMOR SIZE |
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METASTASIS -PATHWAYS-
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SEEDING OF BODY CAVITIES
LYMPHATIC SPREAD HEMATOGENOUS SPREAD IATROGENIC TRANSPLANTATION |
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SEEDING OF BODY CAVITIES
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CELLS DETACH AND FLOAT IN BODY CAVITY FLUID
ATTACH TO BODY WALL, ORGANS OVARIAN TUMORS, PENETRATING BOWEL CANCERS |
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LYMPHATIC SPREAD
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FAVORED ROUTE OF CARCINOMAS
CELLS PENETRATE THIN WALLED LYMPHATIC VESSELS DRAIN TO REGIONAL LYMPH NODES (“SENTINEL LYMPH NODE”) OFTEN CAUSE LYMPHADENOPATHY (ENLARGEMENT OF LYMPH NODES; MAY ALSO BE REACTIVE) |
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HEMATOGENOUS SPREAD
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FAVORED ROUTE FOR SARCOMAS &CARCINOMAS
VEINS > ARTERIES EMBOLIZES TO NEXT CAPILLARY BED (LUNGS AND LIVER ARE FAVORED SITES; METASTATIC CANCER IS MORE COMMON THAN PRIMARY CANCER IN THESE SITES!) SOME HAVE PREFERRED SITES (LUNG CANCER → ADRENALS AND BRAIN PROSTATE CANCER → BONE) SOME SITES RARELY AFFECTED (SKELETAL MUSCLE, HEART, KIDNEY) |
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NEW CASES OF CANCER DIAGNOSED IN THE U.S. EACH YEAR
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ABOUT 1,400,000
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CAUSES OF DEATH IN U.S.
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HEART DISEASE
CANCER STROKE RESPIRATORY DISEASE ACCIDENTS |
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BASAL CELL CARCINOMA OF SKIN STATS
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IS THE MOST COMMON FORM OF CANCER – BY FAR!
ITS HAS A HIGH SURVIVAL RATE (90%+ FIVE YEAR SURVIVAL) IF INCLUDED IN CANCER STATS IT WOULD SKEW THE STATISTICS ACS DECIDED TO IGNORE IT |
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INCIDENCE OF CANCER -MALES-
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55% OF ALL CANCERS
SITES : PROSTATE – 33% LUNG – 13% COLON/RECTUM – 10% |
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INCIDENCE OF CANCER -FEMALES-
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45% OF ALL CANCERS
SITES: BREAST – 31% LUNG – 12% COLON/RECTUM – 11% |
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MORTALITY OF CANCER -MALES-
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OVERALL SURVIVAL = 58%
MOST LETHAL SITES: LUNG – 31% COLON/RECTUM – 10% PROSTATE – 9% |
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MORTALITY OF CANCER -FEMALES-
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OVERALL SURVIVAL = 62%
MOST LETHAL SITES: LUNG – 26% BREAST – 15% COLON/RECTUM – 10% |
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CANCER RATE TRENDS
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STEADY INCREASE IN LUNG CA (SMOKING)
MARKED DECLINE IN UTERINE CERVICAL CA (ROUTINE PAP SMEARS) STEADY DECLINE IN STOMACH CA (UNKNOWN REASONS) SLIGHT DECLINE IN BOWEL CA (RECENT) VERY SLIGHT DECLINE IN LUNG CA (RECENT) |
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GEOGRAPHIC VARIABLES
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ENVIRONMENT CAUSES MUTATIONS (MUTATIONS CAUSE CANCER)
CHANGE OF ENVIRONMENT CHANGES RISK (IMMIGRANTS ASSUME RISK OF NEW LOCATION) MANY ENVIRONMENTAL CARCINOGENS HAVE BEEN IDENTIFIED MANY SOCIAL HABITS ARE CARCINOGENIC (TOBACCO, ALCOHOL, BETEL NUT) SOME SEXUALLY TRANSMITTED (HPV) |
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INTERESTING GEOGRAPHIC FACTS
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NASOPHARYNGEAL CARCINOMA - HONG CONG
ESOPHAGUS - FEMALES IN N. IRAN STOMACH - JAPAN COLORECTAL - UNITED STATES LIVER - SUB-SARAHAN AFRICA SKIN - NORTHERN AUSTRALIA BREAST - EUROPE AND U.S. PROSTATE - U.S. BLACKS BURKITT’S LYMPHOMA - EQUITORIAL AFRICA |
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EPIDEMIOLOGY OF CANCER -AGE-
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INCIDENCE INCREASES WITH AGE
INCREASED LONGIVITY = INCREASED CANCER RATE 80% OCCUR BETWEEN AGES 55-75 REASONS: ACCUMULATION OF MUTATIONS, REDUCED IMMUNOCOMPETENCY RATES DECLINE AFTER AGE 75 |
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CHILDHOOD CANCERS
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LEUKEMIAS
CNS TUMORS LYMPHOMAS SOFT TISSUE SARCOMAS BONE SARCOMAS (OSTEOSARCOMA, EWING’S SARCOMA) NEUROBLASTOMA, PHEOCHROMOCYTOMA, WILM’S TUMOR |
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EPIDEMIOLOGY OF CANCER -RACE-
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WHITE:
30% GET CANCER 40% SURVIVAL RATE NON-WHITE: 32% GET CANCER 25% SURVIVAL RATE |
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CANCER EPIDEMIOLOGY -HEREDITY-
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ONLY SMALL % INHERITED
INHERITED CANCER SYNDROMES (AUTOSOMAL DOMINANT PATTERN; GREATLY ↑ RISK OF CANCER) FAMILIAL CANCERS (RUN IN FAMILIES; NO DEFINITE INHERITANCE PATTERN; BREAST, COLON, OVARY, BRAIN) DEFECTIVE DNA REPAIR SYNDROMES (CHROMOSOMAL/DNA INSTABILITY; XEROSTOMIA PIGMENTOSA) |
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INHERITED CA SYNDROMES
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RETINOBLASTOMA
ADENOMATOUS POLYPOSIS NEUROFIBROMATOSIS MULTIPLE ENDOCRINE NEOPLASIA SYDNROMES BASAL CELL NEVUS SYNDROME |
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RETINOBLASTOMA
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MALIGNANT NEOPLASM OF THE EYE
40% ARE INHERITED MUTATION IN RB TUMOR SUPPRESSOR GENE 10,000X RISK BILATERAL TUMORS OFTEN DEVELOP ALSO RISK OF OSTEOGENIC SARCOMA |
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ADENOMATOIS POLYPOSIS
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APC TUMOR SUPPRESSOR GENE
NUMEROUS COLONIC POLYPS 100% DEVELOP CA WITHOUT TX! |
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NEUROFIBROMATOSIS
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NF1 OR NF2 GENE MUTATIONS
MULTIPLE NEUROFIBROMAS CAFÉ-AU-LAIT SPOTS NEUROFIBROSARCOMA DEVELOPS |
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MULTIPLE ENDOCRINE NEOPLASIA SYNDROMES
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TYPES 1 AND 2 PRIMARILY
MEN1 OR RET GENE MUTATIONS NEURAL/ENDOCRINE ANOMALIES (100% DEVELOP MUCOSAL NEUROMAS) MEDULLARY THYROID CARCINOMA PHEOCHROMOCYTOMA OF ADRENAL |
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BASAL CELL CARCINOMA SYNDROME
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PATCH GENE MUTATION
BASAL CELL CARCINOMAS JAW CYSTS (ODONTOGENIC KERATOCYSTS) SKELETAL ANOMALIES (BIFID RIBS) |
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XEROSTOMIA PIGMENTOSA
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INABILITY TO REPAIR DNA
SUN-INDUCED SKIN CANCER RISK OF OTHER CANCERS |
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PERSISTENT CELL REPLICATION
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ACQUIRED PRE-NEOPLASTIC CONDITION
SCC IN UNHEALED WOUNDS HEPATOCELLULAR CA IN CIRRHOSIS |
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HYPERPLASTIC/DYSPLASTIC PROLIFERATIONS
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ACQUIRED PRE-NEOPLASTIC CONDITION
ENDOMETRIAL HYPERPLASIA → ENDOMETRIAL CA METAPLASIA/DYSPLASIA BRONCHUS → LUNG CA |
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CHRONIC ATROPHIC GASTRITIS
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ACQUIRED PRE-NEOPLASTIC CONDITION
PERNICIOUS ANEMIA Helicobacter pylori |
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CHRONIC ULCERATIVE COLITIS
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ACQUIRED PRE-NEOPLASTIC CONDITION
COLORECTAL CA |
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LEUKOPLAKIA OF MUCOSAL SURFACES
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ACQUIRED PRE-NEOPLASTIC CONDITION
SCC OF MOUTH, VULVA, PENIS |
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VILLOUS ADENOMA OF THE COLON
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ACQUIRED PRE-NEOPLASTIC CONDITION
COLORECTAL CA |
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CARCINOGENESIS
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THE MOLECULAR BASIS OF CANCER
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MOLECULAR BASIS OF CANCER -FUNDAMENTAL PRINCIPLES-
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NON-LETHAL GENETIC DAMAGE CAUSES CANCER
TUMORS ARISE FROM CLONAL EXPANSION OF A MUTATED PROGENITOR CELL CARCINOGENESIS IN A MULTISTEP PROCESS REGULATORY GENES ARE THE TARGETS FOR GENETIC DAMAGE |
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NON-LETHAL GENETIC DAMAGE CAUSES CANCER
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ACQUIRED FROM ENVIRONMENT (CHEMICALS, RADIATION, VIRUSES)
INHERITED |
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TUMORS ARISE FROM CLONAL EXPANSION OF A MUTATED PROGENITOR CELL
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TUMORS ARE MONOCLONAL IN ORIGIN
MUTATIONS CONFER GROWTH AND SURVIVAL ADVANTAGES TUMORS BECOME HETEROGENOUS AS THEY DEVELOP AVERAGE CANCER HAS 9O MUTATIONS HUNDREDS OF CANCER-ASSOCIATED GENES HAVE BEEN IDENTIFIED: p53 MUTATED IN MANY CANCERS; c-ABL SPECIFIC FOR ONE CANCER (CML); EACH CAUSES DYSREGULATION |
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CARCINOGENESIS IN A MULTISTEP PROCESS
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BOTH PHENOTYPE AND GENOTYPE CHANGES OCCUR
KARYOTYPE CHANGES MAY BE DETECTABLE: TRANSLOCATIONS (CML), DELETIONS, GENE AMPLIFICATIONS MULTIPLE MUTATIONS ACCUMULATE (SUBCLONES; A SINGLE GENE MUTATION WILL NOT CAUSE CANCER) TUMOR “EVOLVES” OVER TIME TUMOR ATTAINS MULTIFACETED ABILITIES ACCOUNTS FOR ↑ AGGRESSIVENESS |
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ABILITIES ACQUIRED BY CANCERS
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ABILITY TO INVADE
INCREASED RATE OF GROWTH ABILITY TO METASTASIZE ANTIGENICITY (OR LACK THEREOF) HORMONAL RESPONSIVENESS SUSCEPTIBILITY TO ANTI-NEOPLASTIC DRUGS |
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REGULATORY GENE TARGETS
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PROTO-ONCOGENES
TUMOR SUPPRESSOR GENES GENES REGULATING APOPTOSIS GENES INVOLVES IN DNA REPAIR |
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PROTO-ONCOGENES
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GROWTH-PROMOTING GENES
MUTANT ALLELES = ONCOGENES SINGLE ALLELE MUTATION CAN CAUSE CANCER (“DOMINANT”) |
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TUMOR SUPPRESSOR GENES
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GROWTH-INHIBITING GENES
BOTH ALLELES MUST MUTATE (“RECESSIVE”) SOME ACT AS PROMOTOR GENES (MUTATION ALLOWS PROLIFERATION; RB AND p53 ARE EXAMPLES) SOME ACT AS CARETAKER GENES (INVOLVED IN DNA REPAIR) |
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GENES THAT REGULATE APOPTOSIS
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NO APOPTOSIS – NO REMOVAL OF MUTATED CELLS
SOME DOMINANT SOME RECESSIVE (LIKE TUMOR SUPPRESSOR GENES) |
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DNA REPAIR GENES
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CARETAKER GENES
MUTATATION ALLOWS WIDESPREAD MUTATIONS IN GENOME ALLOW OTHER MUTATIONS TO SURVIVE (MUTATOR PHENOTYPE) OFTEN FIRST MUTATIONS TO OCCUR |
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PHYSIOLOGIC CHANGES LEADING TO MALIGNANCY
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SELF-SUFFICIENCY IN GROWTH FACTORS
INSENSITIVITY TO GROWTH INHIBITION EVASION OF APOPTOSIS LIMITLESS REPLICATION POTENTIAL SUSTAINED ANGIOGENESIS ABILITY TO INVADE AND METASTASIZE GENETIC INSTABILITY |
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NORMAL CELL PROLIFERATION
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GROWTH FACTOR BINDS TO RECEPTOR
SIGNAL-TRANSDUCING PROTEINS ACTIVATED SIGNAL TRANSMITTED TO NUCLEUS INDUCTION OF DNA TRANSCRIPTION CELL ENTERS CELL CYCLE CELL DIVISION OCCURS |
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OVERVIEW OF ONCOGENES
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PROMOTE AUTOMATOUS GROWTH IN CANCER CELLS
PROTO-ONCOGENE MUTATES INTO AN ONCOGENE ONCOGENES PRODUCE ONCOPROTEINS (DEVOID OF REGULATORY ELEMENTS; DO NOT DEPEND ON GROWTH FACTORS; ONE ALLELE MUTATION IS ENOUGH) ONCOPROTEINS PROMOTE CELL GROWTH |
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SELF-SUFFICIENCY IN GROWTH SIGNALS -HOW THEY DO IT-
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GROWTH FACTORS
GROWTH FACTOR RECEPTORS SIGNAL-TRANDUCING PROTEINS NUCLEAR TRANSCRIPTION FACTORS CYCLINS AND CDKs |
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GROWTH FACTORS
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CANCER CELLS ACQUIRE ABILITY TO SYNTHESIZE GROWTH FACTORS
CELLS DEVELOP AUTOCRINE LOOPS: INDEPENDENT OF OTHER CELLS; PDGF IN SARCOMAS; FGF IN GI/BREAST/MELANOMAS |
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GROWTH FACTOR RECEPTORS
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CANCER CELLS DEVELOP MUTANT GROWTH FACTOR RECEPTORS (CONTINUOUS MITOGENIC SIGNALS)
OVEREXPRESSION OF GROWTH FACTOR RECEPTORS: HYPERRESPONSIVENESS TO GF EGF IN SCC OF LUNG/H&N HER2/NEU IN BREAST CA (POOR PROGNOSIS; ANTI HER2.NEU ANTIBODIES USED) |
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SIGNAL-TRANSDUCING PROTEINS
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MUTATIONS CREATE SIGNALING PATHWAYS FOR GF RECEPTORS
COMMON MECHANISM IN CANCERS |
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RAS PROTO-ONCOGENE
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SIGNAL-TRANSDUCING PROTEIN
MOST COMMON MECHANISM RAS PROTEINS PERMANENTLY ACTIVATED STIMULATES CELL CYCLE PROGRESSION |
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ABL PROTO-ONCOGENE
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SIGNAL-TRANSDUCING PROTEIN
TYROSINE KINASE SIGNAL TRANSDUCTION ABL GENE TRANSLOCATED FROM CH 9 TO CH 22 TRANSLOCATED PORTION FUSES WITH BCR REGION BCR-ABL HYBRID PROTEIN UNREGULATES TK TK ACTIVITY FAVORS CELL PROLIFERATION ALSO IMPAIRS APOPTOSIS CAUSES CML INHIBITOR OF BCR-ABL PROTEIN USED TO TX CML |
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NUCLEAR TRANSCRIPTION FACTORS
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MUTATION OF GENES REGULATING DNA TRANSCRIPTION
MYC PROTO-ONCOGENE (BURKITT’S LYMPHOMA; BREAST, COLON, LUNG) PROTEINS FAVOR SUSTAINED PROLIFERATION (ACTIVATE CYCLIN-DEPENDENT KINASES; SUPPRESSES CDK INHIBITORS; ALLOWS CELL CYCLE PROGRESSION) |
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CYCLINS AND CDKs
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CYCLINS REGULATE CELL CYCLE
DYSREGULATION FAVOR CELL PROLIFERATION CYCLIN D GENES OVEREXPRESSED IN MANY CANCERS SOME DOWN-REGULATE CDK INHIBITORS |
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INSENSITIVITY TO GROWTH-INHIBITORY SIGNALS
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TUMOR SUPPRESSOR GENES
NORMALLY INHIBIT CELL PROLIFERATION MUTATIONS REMOVE INHIBITION (ALLOW ENTRY INTO CELL CYCLE) LOSS OF CELL CYCLE CONTROL IS FUNDAMENTAL TO MALIGNANCY ALMOST ALL CANCERS DISABLE THE G1 CHECKPOINT |
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RB GENE
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TUMOR SUPPRESSOR GENE
60% RETINOBLASTOMAS SPORATIC 40% ARE INHERITED TWO-HIT HYPOTHESIS RB ENFORCES THE G1 GAP |
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RB TWO-HIT HYPOTHESIS
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TWO MUTATIONS REQUIRED TO PRODUCE RETINOBLASTOMA
FAMILIAL CASES: ONE DEFECTIVE COPY IS INHERITED; SOMATIC MUTATION SUPPRESSES THE OTHER ALLELE; LIKE AUTOSOMAL DOMINANT TRANSMISSION SPORATIC CASES: REQUIRES TWO SOMATIC MUTATIONS; HOST MUST LOSE HETEROZYGOSITY TO GET TUMOR; MUST BECOME HOMOZYGOUS FOR MUTANT ALLELE |
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RB ENFORCES G1 GAP
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DNA REPLICATION REQUIRES CYCLIN E/CDK2 ACTIVITY
EXPRESSION OF CYCLIN E DEPENDS ON E2F TF ACTIVE RB INHIBITS E2F AND PREVENTS TRANSCRIPTION OF CYCLIN E MUTATION INACTIVATES RB… ACTIVATES E2F… TRANSCRIPTION OF CYCLIN E… DNA REPLICATION AS CELLS ENTER S PHASE RB ALSO BINDS OTHER TRANSCRIPTION FACTORS TO CAUSE LOSS OF NORMAL CELL CYCLE REGULATION SOME DNA VIRUSES BIND TO RB… CELLS NOT INHIBITED BY ANTIGROWTH FACTORS |
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p53 GENE
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TUMOR SUPPRESSOR GENE
“GUARDIAN OF THE GENOME” 70% OF CANCERS HAVE p53 MUTATION (LUNG, COLON, BREAST CANCER |
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p53 GENE NORMALLY
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SENSES DNA DAMAGE: ALLOWS DNA REPAIR, BLOCKS REPLICATION OF FAULTY DNA, REMOVES DEFECTIVE CELLS
BLOCKS NEOPLASTIC TRANSFORMATION: INDUCES QUIESCENCE, INDUCES SENESCENCE, INDUCES APOPTOSIS |
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p53 MUTATION RESULTS IN
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FAILURE TO ACTIVATE p53 GENES
NO CELL CYCLE ARREST, DNA REPAIR, SENESCENCE ALLOWS MUTANT CELLS TO REPLICATE |
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LI-FRAUMENI SYNDROME
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INHERIT MUTANT p53
DEVELOP MULTIPLE CANCERS BY AGE 50 |
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TRANSFORMING GROWTH FACTOR-ß PATHWAY
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NORMALLY BLOCK CELL PROLIFERATION
MUTATION BLOCKS ANTIPROLIFERATIVE SIGNALS TO NUCLEUS 100% OF PANCREATIC CANCERS 83% OF COLON CANCERS |
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ADENOMATOUS POLYPOSIS COLI-ß-CATENIN PATHWAY
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LOSS OF APC GENE
TUMOR SUPPRESSOR GENE APC GENE NORMALLY: BLOCKS PROLIFERATION BY DEGRADING ß-CATENIN; WNT SIGNALING MOLECULE PREVENTS ß-CATENIN DEGRADATION MUTATION ALLOWS CONSTANT PROLIFERATION WITHOUT WNT |
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NORMAL APOPTOSIS
EXTRINSIC PATHWAY |
DEATH RECEPTOR PATHWAY
RECEPTOR ACTIVATES CASPASES CASPASES DESTROY DNA & CYTOSKELETON |
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NORMAL APOPTOSIS INTRINSIC PATHWAY
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MITOCHONDRIAL PATHWAY
↑ PERMEABILITY OF MITOCHONDRIAL MEMBRANE (MORE BAX AND BAK MOLECULES; FEWER BCL2 AND BCL-XL MOLECULES) MITOCHONDRIA LEAK CYTOCHROME c CYTOCHROME c ACTIVATES CASPASES |
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EVASION OF APOPTOSIS
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GENE MUTATIONS FRUSTRATE APOPTOSIS
FLIP PROTEINS BIND DEATH RECEPTORS BCL2 PROTECTS LYMPHOCYTES FROM APOPTOSIS (SEEN IN 85% OF B-CELL LYMPHOMAS) |
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NORMAL CELL REPLICATION POTENTIAL
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HAVE A CAPACITY FOR 60-70 DOUBLINGS
GO INTO SENESCENCE AFTERWARDS DUE TO SHORTENING OF TELOMERES RECOGNIZED AS DNA DAMAGE p53 AND RB ARREST CELL CYCLE |
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CANCER CELL REPLICATION POTENTIAL
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TELEROMERASE UPREGULATION
TELOMERES DO NOT SHORTEN ALLOWS CELLS TO CONTINUE DIVIDING SEEN IN 85-95% OF CANCERS |
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SUSTAINED ANGIOGENESIS
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ADEQUATE VASCULAR SUPPLY ESSENTIAL TO TUMOR SURVIVAL
COULD NOT ENLARGE OVER 1-2mm p53… ALSO REGULATE ANGIOGENESIS |
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NORMAL ANGIOGENESIS
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HYPOXIA → VEGF → HIF1α → ANGIOGENESIS
VHL DEGRADES HIF1α ≠ ANGIOGENESIS |
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CANCER CELL ANGIOGENESIS
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VHL MUTATION ALLOWS ANGIOGENESIS
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ANGIOGENIC INHIBITORS FOR TX
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ANGIOSTATIN
ENDOSTATIN VASCULOSTATIN |
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INVASION & METASTASIS -STEPS-
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PRIMARY TUMOR DEVELOPS
INVASION OF ECM VASCULAR DISSEMINATION EVASTATION ANGIOGENESIS AND GROWTH |
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DEVELOPMENT OF PRIMARY TUMOR
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INITIAL MUTATION OCCURS
CLONAL EXPANSION GROWTH DIVERSIFICATION ANGIOGENESIS |
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INVASION OF ECM: DETACHMENT
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(“LOOSENING UP”)
MUTATION OF E-CADHERIN GENES LOSS OF E-CADHERIN FUNCTION EXPRESSION OF SNAIL OR TWIST |
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INVASION OF ECM: DEGRADATION OF ECM
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SECRETION OF PROTEOLYTIC ENZYMES (PROTEASES)
COLLAGENASE ACTIVITY GREATED IN CA CELLS |
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INVASION OF ECM: ATTACHMENT TO ECM COMPONENTS
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FIBRINECTIN
LAMININ |
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INVASION OF ECM: MIGRATION OF CELLS
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CYTOKINASE INDUCES CYTOEKELETON CHANGES
CHEMOTAXIS EFFECT FROM CLEAVED ECM |
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VASCULAR DISSEMINATION
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INTRAVASTATION (CELLS EXIT ECM INTO BLOODSTREAM; PROCESS SIMILAR TO INVASION)
CELLS/AGGREGATES EMBOLIZE VASCULAR/LYMPHATIC DRAINAGE PREDICTS METASTATIC SITE MOST LODGE IN FIRST CAPILLARY BED ENCOUNTERED (USUALLY LUNGS OR LIVER) PATTERN OF SPREAD NOT ALWAYS PREDICTABLE (LUNG CANCER → ADRENAL GLANDS; HOMING DETERMINED BY RECEPTORS/LIGANDS) |
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GENOMIC INSTABILITY
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DEFECTS ENABLE CANCER TO PERSIST
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DEFECT IN MISMATCH REPAIR
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GENOMIC INSTABILITY
FAILURE TO REPAIR NUCLEOSIDE MISMATCHES HEREDITARY NONPOLYPOSIS COLON CANCER ALLOWS ERRORS TO ACCUMULATE |
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DEFECT IN NUCLEOSIDE EXCISION REPAIR
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GENOMIC INSTABILITY
NO REPAIR OF PYRIMIDINE CROSS-LINKAGES XERODERMA PIGMENTOSA |
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DEFECTS IN RECOMBINATION REPAIR
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GENOMIC INSTABILITY
HYPERSENSITIVITY TO DNA-DAMAGING AGENTS BRCA1 AND BRCA2 IN BREAST CANCER |
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CARCINOGENIC AGENTS
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CHEMICALS
RADIATION MICROBIAL AGENTS |
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CHEMICAL CARCINOGENS: DIRECT-ACTING AGENTS
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REQUIRE NO CONVERSION
MANY AGENTS MOST WEAK CARCINOGENS SOME CA TX NOW CARCINOGENIC |
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CHEMICAL CARCINOGENS: INDIRECT-ACTING AGENTS
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REQUIRE CONVERSION (PROCARCINOGENS)
EXAMPLES: POLYCYCLIC HYDROCARBONS – LUNG CA AROMATIC AMINES – BLADDER CA AFLATOXIN B1 – HEPATOCELLULAR CA |
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CHEMICAL CARCINOGENESIS -MECHANISMS--
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GENETICS DETERMINES INDIVIDUAL SUSCEPTIBILITY
MOST ARE MUTAGENIC USUALLY RAS & p53 MUTATIONS SOME ACT AS INITIATORS AUGUMENTED BY PROMOTERS: INITIATOR CAUSES MUTATION PROMOTER → CLONAL EXPANSION SUBSEQUENT MUTATIONS → CANCER |
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CARCINOGENESIS -PHASES-
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INITIATION PHASE (CARCINOGEN ACTS; MUTATIONS OCCUR)
PROMOTING PHASE (CELLS PROLIFERATE; CLONAL EXPANSION) PROGRESSIVE PHASE - AUTONOMY TUMOR PHASE (CLINICAL NEOPLASM; CAN INVADE AND METASTASIZE) |
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RADIATION CARCINOGENESIS
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UV RAYS FROM SUNLIGHT
X-RAYS NUCLEAR FISSION RADIONUCLEOTIDES |
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RADIATION CARCINOGENESIS EVIDENCE OF CARCINOGENICITY
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RADIUM MINERS HAVE 10X RISK OF LUNG CA
WWII SURVIVORS AND LEUKEMIA… CANCERS IN AREA OF CHERNOBYL THYROID CA FOLLOWING H&N IRRADIATION |
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RADIATION CARCINOGENESIS MECHANISMS
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CHROMOSOME BREAKAGE
TRANSLOCATIONS POINT MUTATIONS PYRIMIDINE DIMERS (XERODERMA PIGMENTOSA) |
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MICROBIAL CARCINOGENS
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ONCOGENIC RNA VIRUSES
ONCOGENIC DNA VIRUSES Helicobacter Pylori |
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ONCOGENIC RNA VIRUSES
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HUMAN T-CELL LEUKEMIA VIRUS (HTLV-1)
T-CELL LEUKEMIA/LYMPHOMA TRANSMITTED SEXUALLY, BLOOD, BREAST MILK 3-5% INFECTED GET DISEASE LONG LATENT PERIOD (20-50 YEARS) |
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HUMAN PAPILLOMAVIRUS
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ONCOGENIC DNA VIRUS
BENIGN SQUAMOUS PAPILLOMAS (WARTS) SCC OF UTERINE CERVIX OROPHARYNGEAL CA INTERACT WITH ONCOGENES AND TUMOR SUPPRESSOR GENES |
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EPSTEIN-BARR VIRUS
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ONCOGENIC DNA VIRUS
BURKITT’S LYMPHOMA B-CELL LYMPHOMA IN AIDS NASOPHARYNGEAL CA |
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HEPATITIS B VIRUS
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ONCOGENIC DNA VIRUS
HEPATOCELLULAR CA |
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ONCOGENIC DNA VIRUSES
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HUMAN PAPILLOMA VIRUS
EPSTEIN-BARR VIRUS HEPATITIS B VIRUS KAPOSI’S SARCOMA HERPESVIRUS |
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HELICOBACTER PYLORI
|
GASTRIC ADENOCARCINOMA (GASTRITIS… CELL PROLIFERATION)
GASTRIC LYMPHOMA (REACTIVE T CELLS… B CELL LYMPHOMA; MALT LYMPHOMA) |
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TUMOR ANTIGENS
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ANTIGENS ON TUMOR CELLS THAT ELICIT AN IMMUNE RESPONSE
TYPES: TUMOR-SPECIFIC ANTIGENS (ONLY ON TUMOR CELLS) TUMOR-ASSOCIATED ANTIGENS (ON TUMOR CELLS AND NORMAL CELLS) |
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TUMOR ANTIGENS -TYPES-
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PRODUCTS OF MUTATED GENES
OVER/ABERRANTLY EXPRESSED PROTEINS PRODUCTS OF ONCOGENIC VIRUSES ONCOFETAL ANTIGENS ALTERED CELL-SURFACE MOLECULES CELL TYPE-SPECIFIC DIFFERENTIATION ANTIGENS |
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PRODUCTS OF MUTATED GENES -ONCOGENES AND TS GENES-
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ß-CATENIN, RAS, p53, CDK4…
SHARED BY MANY TUMORS DO NOT ELICIT PROTECTIVE IMMUNE RESPONSES |
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PRODUCTS OF MUTATED GENES -OTHER GENES-
|
DUE TO GENETIC INSTABILITY
LEADS TO MANY MUTATIONS EXTREMELY DIVERSE ANTIGENS OFTEN OCCUR IN CHEMICAL OR RADIATION-INDUCED CANCERS CAN BE TARGETED BY IMMUNE SYSTEM |
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OVER/ABERRANTLY EXPRESSES CELLULAR PROTEINS
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OVER-EXPRESSES NORMAL PROTEINS (TYROSINE IN MELANOMAS; MAY ELICIT IMMUNE RESPONSE)
ANTIGENS THAT ARE NORMALLY SILENT (“CANCER-TESTIS” ANTIGENS; ONLY EXPRESSES IN TESTIS; USUALLY TUMOR-SPECIFIC ANTIGENS) |
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ANTIGENS PRODUCED BY ONCOGENIC VIRUSES
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ANTIGENS ON ONCOGENIC VIRUSES
USUALLY DNA VIRUSES MAY INDUCE PROTECTIVE IMMUNE RESPONSE BASIS FOR HPV VACCINES |
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ONCOFETAL ANTIGENS
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ANTIGENS FROM EMBRYOGENESIS
NOT NORMALLY EXPRESSED IN ADULTS MUTATIONS INHIBIT SUPPRESSION AND ALLOW PROTEIN PRODUCTION CARCINOEMBRYONIC ANTIGEN, α-FETOPROTEIN LIVER AND LUNG CANCERS USED FOR DETECTION AND MONITORING CANCERS |
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ALTERED CELL SURFACE MOLECULES
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GLYCCOLIPIDS/GLYCOPROTEINS
HIGHER AMOUNT ON TUMOR CELLS GANGLIOSIDES, BLOOD GROUP ANTIGENS, MUCINS… MAY BE USED DIAGNOSTICALLY MAY BE TARGETS FOR TX |
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CELL TYPE -SPECIFIC DIFFERENTIATION ANTIGENS
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ANTIGENS PRESENT ON CELLS OF ORIGIN
B OR T-CELL MARKERS (CD10, CD20) DO NOT INDUCE IMMUNE RNX |
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ANTITUMOR EFFECTOR MECHANISMS
|
CELL-MEDIATED IMMUNITY
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CYTOTOXIC T LYMPHOCYTES
|
ANTITUMOR EFFECTOR MECHANISMS
PROTECTIVE AGAINST VIRUS-ASSOCIATED TUMORS |
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NATURAL KILLER CELLS
|
ANTITUMOR EFFECTOR MECHANISMS
1ST LINE OF DEFENSE AGAINST TUMOR CELLS DESTROY TUMOR WITHOUT PRIOR SENSITIZATION ACTIVATED BY IL-2 |
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MACROPHAGES
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ANTITUMOR EFFECTOR MECHANISMS
COLLABORATE WITH OTHER CELLS |
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HUMEROL MECHANISMS
|
ANTITUMOR EFFECTOR MECHANISMS
MONOCLONAL ANTIBODIES FOR TX CD20 FOR NON-HODGKINS LYMPHOMA |
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IMMUNE SURVEILLANCE
|
CANCER IS MORE COMMON IN INNUMODEFICIENT HOSTS
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CANCER IS MORE COMMON IN IMMUMODEFICIENT HOSTS:
|
CONGENITAL IMMUNODEFICIENCY, IMMUNOSUPPRESSED TRANSPLANT PATIENTS, AIDS VICTIMS, MOST ARE LYMPHOMAS
TUMORS BECOME ANTIGEN NEGATIVE AS THEY PROGRESS (STRONGLY IMMUNOGENIC CELLS ARE ELIMINATED) LOSS/REDUCED EXPRESSION OF HISTOCOMPATIBLE MOLECULES (FAILURE TO EXPRESS HLA CLASS I; NO CYTOTOXIC T LYMPHOCYTE ACTIVATION) IMMUNOSUPPRESSION (CARCINOGENIC AGENTS SUPPRESS IMMUNE RESPONSE; TUMOR PRODUCTS MAY BE IMMUNOSUPPRESSIVE (TGF-ß)) |
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NEOPLASIA HORMONAL PRODUCTION
|
TUMORS MAY SECRETE HORMONES:
BENIGN > MALIGNANT WELL DIFFERENTIATED > POOR HORMONE EFFECTS MAY BE THE DOMINANT CLINICAL SYMPTOM EVEN BENIGN TUMORS MAY CAUSE FATAL CONSEQUENCES |
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PARANEOPLASTIC SYNDROMES
|
ELABORATION OF ECTOPIC HORMONES
OCCURS IN 10-15% OF CANCERS MAY BE EARLY MANIFESTATION MAY HAVE SERIOUS (LETHAL) CONSEQUENCES MAY CAUSE DIAGNOSTIC DIFFICULTY COMMON WITH SOME CANCERS (LUNG, BREAST, HEMATOLOGIC CANCERS) VERY DIVERSE SECRETIONS: HYPERCALCEMIA –PTH, BONE DESTRUCTION CUSHING SYNDROME – ACTH NONBACTERIAL THROMBOTIC ENDOCARDITIS SOME TUMORS PRODUCE MULTIPLE HORMONES AND SEVERAL SYNDROMES |
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CANCER CACHEXIA
|
WASTING SYNDROME
LOSS OF BODY FAT & LEAN MASS WEAKNESS, ANOREXIA, ANEMIA |
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CANCER CACHEXIA
|
NOT NUTRITIONAL DEMANDS OF CA
ANOREXIA CONTRIBUTES CYTOKINE (TNF) KEEPS DEMAND HI PROTEOLYSIS-INDUCING FACTOR |
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|
OTHER NEOPLASIA SYMPTOMS
|
ULCERATION
BLEEDING SECONDARY INFECTION INTESTINAL OBSTRUCTION |
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|
NEOPLASIA GRADING AND STAGING
|
USE TO QUALTIFY BIOLOGICAL AGGRESSIVENESS OF A NEOPLASM
USEFUL TO PLAN TX USEFUL TO PREDICT PROGNOSIS |
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NEOPLASIA GRADING
|
MICROSCOPIC OR CYTOLOGIC DIFFERENTIATION
BRODER’S SYSTEM |
|
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BRODER’S SYSTEM
|
WELL DIFFERENTIATED
LEAST LIKELY TO METASTASIZE BEST PROGNOSIS |
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BRODER’S SYSTEM
|
MODERATELY DIFFERENTIATED
MAY METASTASIZE INTERMEDIATE PROGNOSIS |
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BRODER’S SYSTEM
|
POORLY DIFFERENTIATED
LIKELY TO METASTASIZE BAD PROGNOSIS |
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BRODER’S SYSTEM
|
VERY POORLY DIFFERENTIATED
VERY LIKELY TO METASTASIZE WORST PROGNOSIS |
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NEOPLASIA STAGING
|
BASED ON CLINICAL/RADIOGRAPHIC EXTENT OF TUMOR
BETTER THAN GRADING TNM AND AJC SYSTEMS |
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NEOPLASIA STAGING
|
SIZE OF PRIMARY TUMOR
INVOLVEMENT OF REGIONAL LYMPH NODES DISTANT METASTASIS |
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NEOPLASIA MORPHOLOGIC DIAGNOSIS
|
BIOPSY
FINE NEEDLE ASPIRATION CYTOLOGY SMEARS IMMUNOHISTOCHEMISTRY FLOW CYTOMETRY |
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|
NEOPLASIA LABORATORY DIAGNOSIS
|
MORPHOLOGIC METHODS
TUMOR MARKERS MOLECULAR DIAGNOSIS MOLECULAR PROFILING |
|
|
NEOPLASIA BIOPSY
|
EXCISION OF TISSUE:
INCISIONAL – REMOVE PART EXCISIONAL – REMOVE ALL “GOLD STANDARD” FOR DIAGNOSIS H&E AND SPECIAL STAINS USED FROZEN SECTION DIAGNOSIS |
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NEOPLASIA CYTOLOGY SMEARS
|
PAPANICOLAUO SMEARS
UTERINE CERVIX, ENDOMETRIAL, BRONCHIAL CANCERS CANNOT EVALUATE INVASION! |
|
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NEOPLASIA FINE NEEDLE ASPIRATION
|
ASPIRATION OF CELLS
MINIMALLY INVASIVE PROCEDURE USED FOR SUPERFICIAL MASSES BREAST, THYROID, LYMPH NODES, SALIVARY GLANDS, LIVER… SMALL SAMPLE CAN POSE PROBLEMS |
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NEOPLASIA IMMUNOHISTOCHEMISTRY
|
ADJUNCT TO ROUTINE HISTOLOGY
PEROXIDASE-LABELED ANTIBODIES AGAINST TUMOR SPECIFIC ANTIGENS HELPS DIAGNOSE POORLY DIFFERENTIATED TUMORS |
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FLOW CYTOMETRY
|
FLUORESCENT ANTIBODIES AGAINST CELL SURFACE ANTIGENS
LEUKEMIAS AND LYMPHOMAS |
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TUMOR MARKERS
|
BIOASSAYS FOR TUMOR-ASSOCIATED ENZYMES, HORMONES…
USEFUL FOR FINDING TUMORS (NOT SO MUCH FOR DIAGNOSING) MAY LACK SENSITIVITY/SPECIFICITY: PROSTATE SPECIFIC ANTIGEN (PSA) (PROSTATE CANCER) CARCINOEMBRYONIC ANTIGEN (CEA) (COLON CANCER) Α-FETOPROTEIN (HEPATOCELLULAR CARCINOMA) MONITER EFFECTIVENESS OF TX |
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NEOPLASIA MOLECULAR DIAGNOSIS
|
DIAGNOSIS OF MALIGNANCY (FISH/PCR TECHNIQUES)
PREDICTING PROGNOSIS/BEHAVIOR (CERTAIN GENETIC DEFECTS DENOTE POOR PROGNOSIS) DETECTION OF RESIDUAL DISEASE DIAGNOSIS OF HEREDITARY PREDISPOSITION TO CANCER |
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MOLECULAR PROFILING
|
DNA MICROARRAY ANALYSIS (THOUSANDS OF GENES!)
MAY REVEAL TARGETS FOR TX |
|
|
TREATMENT OF NEOPLASMS
|
BENIGN NEOPLASMS (USUALLY CONSERVATIVE EXCISON: “LUMPECTOMY”)
MALIGNANT NEOPLASMS (RADICAL SURGICAL EXCISION) RADIOTHERAPY (POST-RADIATION COMPLICATIONS) CHEMOTHERAPY (CYTOTOXIC DRUGS, METABOLIC INHIBITORS) IMMUNOMODULATION COMBINED THERAPY |
|
|
SKIN CANCER
|
MOST COMMON SITE
LOW MORTALITY SUNLIGHT EXPOSURE BASAL CELL CARCINOMA (IGNORED IN STATISTICS) SQUAMOUS CELL CARCINOMA MELANOMA |
|
|
LUNG CANCER
|
12% OF ALL CANCER
30% OF ALL CANCER DEATHS INCREASING SINCE WWII (SLIGHT DECREASE RECENTLY) WOMEN CATCHING MEN SMOKING |
|
|
COLORECTAL CANCER
|
10% OF ALL CANCER
10% OF ALL CANCER DEATHS SLIGHT DECREASE RECENTLY (ROUTINE COLONOSCOPY) PRE-EXISTING POLYPS HEREDITARY SYNDROMES |
|
|
BREAST CANCER
|
31% OF FEMALE CANCER
15% OF FEMALE CANCER DEATHS HEREDITARY, HORMONES.. |
|
|
UTERINE CERVICAL CANCER
|
ONCE MOST COMMON FEMALE CANCER
DECLINING DUE TO PAP SMEAR |
|
|
PROSTATE CANCER
|
33% OF ALL MALE CANCER
9% OF ALL MALE CANCER DEATHS AFRICAN-AMERICAN MEN PSA SCREENING |
