neoplasia part 2 Flashcards
What is the role of p53 in response to DNA damage?
p53 slows the cell cycle and upregulates DNA repair enzymes.
If repair is not possible, p53 induces apoptosis by:
Upregulating BAX, which disrupts Bcl2.
Causing cytochrome c leakage from mitochondria, activating apoptosis.
What is required for tumor formation involving p53 and what syndrome is assciated with its germline mutation?
Both copies of the p53 gene must be knocked out (Knudson two-hit hypothesis).
Loss is seen in >50% of cancers.
Germline mutation causes Li-Fraumeni syndrome, characterized by multiple carcinomas and sarcomas.
What is the function of Rb (retinoblastoma protein)?
Rb holds E2F, a transcription factor needed for progression from G1 to S phase.
E2F is released when Rb is phosphorylated by the cyclinD/CDK4 complex.
How does Rb mutation contribute to tumor formation?
Rb mutation results in constitutively free E2F, promoting uncontrolled cell growth.
Both Rb gene copies must be knocked out (Knudson two-hit hypothesis).
Sporadic mutation: Unilateral retinoblastoma.
Germline mutation: Familial retinoblastoma (bilateral retinoblastoma and osteosarcoma).
What is the role of Bcl2 in apoptosis?
Bcl2 stabilizes the mitochondrial membrane, blocking cytochrome c release.
Disruption of Bcl2 allows cytochrome c to leak, activating apoptosis.
How does Bcl2 overexpression contribute to follicular lymphoma?
t(14;18) translocation moves Bcl2 (chromosome 18) to the Ig heavy chain locus (chromosome 14).
Increased Bcl2 stabilizes the mitochondrial membrane, preventing apoptosis.
B cells that would normally undergo apoptosis during somatic hypermutation accumulate, leading to lymphoma.
What is the role of telomerase in cancer?
Telomerase prevents telomere shortening, allowing cell immortality.
Normally, telomeres shorten with divisions, causing cellular senescence.
Many cancers upregulate telomerase to preserve telomeres.
What factors are essential for tumor angiogenesis?
FGF (fibroblast growth factor) and VEGF (vascular endothelial growth factor) are commonly produced by tumor cells to promote angiogenesis.
How do tumor cells evade immune surveillance?
Tumors often produce abnormal proteins expressed on MHC class I.
CD8+ T cells detect and destroy mutated cells.
Tumor cells can evade detection by downregulating MHC class I expression.
Immunodeficiency increases the risk of cancer.
What are the steps involved in tumor invasion?
E-cadherin downregulation leads to dissociation of epithelial cells.
Cells attach to laminin and destroy the basement membrane (collagen type IV) using collagenase.
Tumor cells attach to fibronectin in the extracellular matrix and spread locally.
Cells invade vascular or lymphatic spaces for metastasis.
What is the primary route of metastasis for carcinomas?
Lymphatic spread, often to regional draining lymph nodes
What is the primary route of metastasis for sarcomas and some carcinomas?
Hematogenous spread.
Examples of carcinomas with hematogenous spread:
Renal cell carcinoma (invades renal vein).
Hepatocellular carcinoma (invades hepatic vein).
Follicular thyroid carcinoma.
Choriocarcinoma.
What type of cancer is associated with seeding of body cavities?
Ovarian carcinoma, often involving the peritoneum (e.g., “omental caking”).
What are the clinical features of benign tumors?
Slow-growing.
Well-circumscribed and distinct.
Mobile.
Require biopsy or excision for definitive classification.
What is the hallmark of malignancy?
Metastatic potential.
Benign tumors never metastasize, while malignant tumors can.
What tissue type does the Keratin stain target?
Epithelium.
What tissue type does the Vimentin stain target?
Mesenchyme.
What tissue type does the Desmin stain target?
Muscle.
What tissue type does the GFAP stain target?
Neuroglia.
What tissue type does the Neurofilament stain target?
Neurons.
What does the PSA stain target?
Prostatic epithelium.
What does the ER stain target?
Breast epithelium.
What does the Thyroglobulin stain target?
Thyroid follicular cells.
What does the Chromogranin stain target?
Neuroendocrine cells (e.g., small cell carcinoma of the lung and carcinoid tumors).
What does the S-100 stain target?
Melanoma.
Schwannoma.
Langerhans cell histiocytosis.
What is required for diagnosing carcinoma when serum tumor markers (e.g., elevated PSA) are present?
A tissue biopsy is required for diagnosis (e.g., biopsy of prostate with elevated PSA).
What are the two types of cancer grading and their characteristics?
Well-differentiated (low grade) - resembles normal parent tissue.
Poorly differentiated (high grade) - does not resemble parent tissue.
What does cancer staging assess?
It assesses the size and spread of cancer.
When is cancer staging determined?
It is determined after the final surgical resection of the tumor.
