Principles of Neoplasia Flashcards

Question

Nonionizing Radiation

Answer 1

- basal cell carcinoma - squamous cell carcinoma - melanoma of skin - UVB sunlight is most common source - results in formation of pyrimidine dimers in DNA, which are normally excised by restriction endonucleases

Answer 2

- platelet-derived growth factor - mechanism: overexpression, autocrine loop - associated tumor: astrocytoma

Answer 3

- epidermal growth factor receptor - mechanism: amplification - associated tumor: subset of breast carcinomas

Answer 4

- neural growth factor receptor - mechanism: point mutation - associated tumor: MEN2A, MEN2B and sporadic medullary carcinoma of thyroid

Answer 5

- stem cell growth factor receptor - mechanism: point mutation - associated tumor: gastrointestinal stromal tumor (GIST)

Answer 6

- GTP-binding protein - mechanism: point mutation - associated tumor: carcinomas, melanoma, and lymphoma

Answer 7

- tyrosine kinase - mechanism: t(9;22) with BCR - associated tumor: CML and some types of ALL

Answer 8

- transcription factor - mechanism: t(8;14) involving IgH - associated tumor: Burkitt lymphoma

Answer 9

- transcription factor - mechanism: amplification - associated tumor: neuroblastoma

Answer 10

- transcription factor - mechanism: amplification - lung carcinoma (small cell)

Answer 11

- cyclin - mechanism: t(11;14) involving IgH - mantle cell lymphoma

Answer 12

- cyclin-dependent kinase - mechanism: amplification - associated tumor: melanoma

Answer 13

- regulates progression from G1 to S phase - DNA damage --> p53 slows the cell cycle and upregulates DNA repair enzymes - if DNA repair not possible --> induce apoptosis - p53 induces apoptosis by upregulating BAX, which disrupts Bcl2... this then causes cytochrome c to leak from mitochondria and thus activate apoptosis - both copies of the p53 gene must be knocked out for tumor formation - loss is seen in >50% of cancers - germline mutation results in Li-Fraumeni syndrome (2nd hit somatic), characterized by the propensity to develop multiple types of carcinomas and sarcomas

Answer 14

- regulates progression from G1 to S phase - "holds" the E2F transcription factor, which is necessary for transition to the S phase - E2F is released when Rb is phosphorylated by the cyclinD/cyclin-dependent kinase 4 (CDK4) complex - Rb mutation results in constitutively free E2F, allowing progression through the cell cycle and uncontrolled growth of cells - both copies of Rb gene must be knocked out for tumor formation - sporadic mutation (both hits are somatic) is characterized by unilateral retinoblastoma - germline mutation results in familial retinoblastoma (2nd hit is somatic), characterized by bilateral retinoblastoma and osteosarcoma

Answer 15

- prevent apoptosis in normal cells - promote apoptosis in mutated cells whose DNA cannot be repaired - normally stabilizes the mitochondrial membrane, blocking release of cytochrome c - disruption of Bcl2 allows cytochrome c to leave the mitochondria and activate apoptosis

Answer 16

- Bcl2 is overexpressed in follicular lymphoma - t(14,18) moves Bcl2 (chromosome 18) to the Ig heavy chain locus (chrom. 14), resulting in increased Bcl2 - mitochondrial membrane is further stabilized, prohibiting apoptosis - B cells that would normally undergo apoptosis during somatic hyper-mutation in the lymph node germinal center accumulate, leading to lymphoma

Answer 17

- telomerase is necessary for cell immortality - normally, telomeres shorten with serial cell divisions, eventually resulting in cellular senescence - cancers often have upregulated telomerase, which preserves telomeres

Answer 18

- necessary for tumor survival and growth | - FGF and VEGF (angiogenic factors) are commonly produced by tumor cells

Answer 19

- necessary for tumor survival - mutations often result in production of abnormal proteins, which are expressed on MHC class I - CD8+ T cells detect and destroy such mutated cells - tumor cells can evade immune surveillance by downregulating expression of MHC class I - immunodeficiency (both primary and secondary) increases the risk for cancer

Answer 20

- epithelial tumor cells are normally attached to one another by cellular adhesion molecules (e.g. E-cadherin) - downregulation of E-cadherin leads to dissociation of attached cells - cells attach to laminin and destroy basement membrane (collagen type IV) via collagenase - cells attach to fibronectin in the extracellular matrix and spread locally - entrance into vascular or lymphatic spaces allows for metastasis (distant spread)

Answer 21

- lymphatic spread is characteristic of carcinomas | - initial spread is to regional draining lymph nodes

Answer 22

- hematogenous spread is characteristic of sarcomas and some carcinomas - renal cell carcinoma (often invades renal vein) - hepatocellular carcinoma (often invades hepatic vein) - follicular carcinoma of the thyroid - choriocarcinoma

Answer 23

-seeding of body cavities is characteristic of ovarian carcinoma, which often involves the peritoneum

Answer 24

- benign tumors tend to be slow growing, well circumscribed, distinct, and mobile - malignant tumors are usually rapid growing, poorly circumscribed, infiltrative, and fixed to surrounding tissues and local structures - biopsy or excision is generally required before a tumor can be classified as benign or malignant with certainty - some benign tumors can grow in a malignant-like fashion, and some malignant tumors can grow in a benign-like fashion

Answer 25

- usually well differentiated - organized growth - uniform nuclei - low nuclear to cytoplasmic ratio - minimal mitotic activity - lack of invasion (of basement membrane or local tissue) - no metastatic potential

Answer 26

- classically poorly differentiated (anaplastic) - disorganized growth (loss of polarity) - nuclear pleomorphism and hyperchomasia - high nuclear to cytoplasmic ratio - high mitotic activity with atypical mitosis - invasion (through basement membrane or into local tissue) - metastatic potential is the hallmark of malignancy - benign tumors never metastasize - immunohistochemistry is used to characterize tumors that are difficult to classify on histology

Answer 27

- proteins released by tumor into serum (e.g. PSA) - useful for screening, monitoring response to treatment, and monitoring recurrence - elevated levels require tissue biopsy for diagnosis of carcinoma (e.g. biopsy of prostate with elevated PSA)

Answer 28

- microscopic assessment of differentiation (i.e. how much a cancer resembles the tissue in which it grows); takes into account architectural and nuclear features - well differentiated (low grade) resembles normal parent tissue - poorly differentiated (high grade) does not resemble parent tissue - important for determining prognosis; well-differentiated cancers have better prognosis than poorly-differentiated cancers

Answer 29

- assessment of size and spread of a cancer - key prognostic factor; more important than grade - determined after final surgical resection of the tumor - utilizes TNM staging system - T: tumor (size and/or depth of invasion) - N: spread to regional lymph nodes; second most important prognostic factor - M: metastasis; single most important prognostic factor

Answer 30

-epithelium

Answer 31

-mesenchyme

Answer 32

-neuroglia

Answer 33

-prostatic epithelium

Answer 34

-breast epithelium

Answer 35

-thyroid follicular cells

Answer 36

-neuroendocrine cells (e.g. small cell carcinoma of lung and carcinoid tumors)

Answer 37

-melanoma, Schwannoma and Langerhans cell histiocytes