30 Year 3: General Pathology exam questions on ONCOPATHOLOGY MCQs - HALLMARKS OF CANCER for medical students. Includes MCQs, answers, explanations and written q
This MCQ set contains 30 questions on ONCOPATHOLOGY MCQs - HALLMARKS OF CANCER in the Year 3: General Pathology unit. Each question includes the correct answer and a detailed explanation for active recall and exam preparation.
Correct answer: C – Failure to ubiquitinate and destroy HIF-1α in normoxic conditions
In VHL syndrome, mutated VHL protein cannot bind to HIF-1α even in normoxic conditions. This prevents ubiquitination and destruction of HIF-1α, leading to continuous transcription of VEGF and other pro-angiogenic factors, causing excessive angiogenesis even without hypoxia.
Correct answer: B – Oxygen and nutrients cannot diffuse beyond this distance from blood vessels
Tumors cannot enlarge beyond 1-2 mm in diameter without vascularization because this represents the maximal distance across which oxygen, nutrients, and waste can diffuse from blood vessels. The tumor remains dormant until the "angiogenic switch" occurs.
Correct answer: A – Degrades type IV collagen and releases VEGF from ECM pools
MMP-9 is a gelatinase that cleaves type IV collagen (found in epithelial and vascular basement membranes) AND stimulates release of VEGF from ECM-sequestered pools. This dual action promotes both basement membrane degradation and angiogenesis.
Correct answer: B – Leaky, dilated vessels with haphazard connections
Tumor vasculature is characteristically abnormal - vessels are leaky and dilated with a haphazard pattern of connection, unlike the organized structure of normal capillaries. This abnormality contributes to poor perfusion and creates opportunities for metastasis.
Correct answer: B – Induction of thrombospondin-1 (TSP-1) synthesis
Normal p53 induces synthesis of TSP-1, which is a prototypical angiogenesis inhibitor. Loss of p53 function in tumors leads to decreased TSP-1 production, contributing to the angiogenic switch and tumor vascularization.
Correct answer: B – They are produced by proteolytic cleavage of other proteins
These three potent angiogenesis inhibitors are all produced by proteolytic cleavage: angiostatin from plasminogen, endostatin from collagen, and vasculostatin from transthyretin. This shows how proteases can have both pro- and anti-angiogenic effects.
Correct answer: A – Secreting growth factors like insulin-like growth factors and PDGF
Neovascularization has a dual effect: perfusion supplies nutrients AND newly formed endothelial cells stimulate growth of adjacent tumor cells by secreting growth factors such as insulin-like growth factors, PDGF, and GM-CSF. This paracrine signaling enhances tumor proliferation.
Correct answer: D – Colonization and growth at distant sites
Tumor cells are quite inefficient at colonizing distant organs. Millions of tumor cells are shed daily from even small tumors, but gross metastatic lesions don't always develop. The target tissue must provide a receptive stroma, and most sites are non-permissive environments for tumor growth.
Correct answer: A – Loss of intercellular adhesion and loss of β-catenin sequestration
E-cadherin loss promotes metastasis by: (1) loosening tumor cell-to-cell contacts (loss of "intercellular glue"), and (2) failing to sequester β-catenin, which can then promote proliferation. E-cadherin also transmits anti-growth signals when functioning normally.
Correct answer: B – To organs expressing high levels of CXCL12 and CCL21
Organ tropism is partly explained by chemokine receptor-ligand matching. Breast cancer cells expressing CXCR4 and CCR7 preferentially metastasize to organs highly expressing the corresponding ligands (CXCL12 and CCL21), such as bone, lung, and lymph nodes.
Correct answer: B – Loosening of tumor cell-to-cell contacts
The first step in the metastatic cascade is loosening of tumor cell-to-cell contacts, primarily through loss of E-cadherin function. This must occur before cells can detach and begin the invasion process through basement membrane degradation and migration.
Correct answer: B – It generates novel binding sites that promote tumor cell migration
Cleavage of collagen IV and laminin by MMP-2 or MMP-9 generates novel sites that bind to receptors on tumor cells and stimulate migration. The matrix is thus modified in ways that actively promote invasion and metastasis, not just passively allowing passage.
Correct answer: B – The target tissue provides a non-permissive environment
Despite being well-vascularized, skeletal muscles are rarely metastatic sites because the target tissue is non-permissive. This demonstrates that vascularization alone is insufficient - tumor cells depend on a receptive stroma for growth, which skeletal muscle fails to provide.
Correct answer: B – Increased ECM molecules, proteases, and growth factors
Tumor-associated fibroblasts show altered expression of genes encoding ECM molecules, proteases, protease inhibitors, AND various growth factors. This creates a complex, dynamic environment with significant cross-talk between tumor cells, fibroblasts, immune cells, and ECM that promotes tumor progression.
Correct answer: B – Promoting tumor cell motility
HGF/SCF is a paracrine effector of cell motility produced by stromal cells. Its elevated concentration at the advancing edges of highly invasive tumors like glioblastoma supports its role in promoting tumor cell locomotion and invasion.
Correct answer: C – Protection from anti-tumor host effector cells
Aggregated tumor cells are afforded some protection from anti-tumor host effector cells when they form emboli with circulating leukocytes and platelets. However, most tumor cells circulate as single cells, which are more vulnerable.
Correct answer: B – Malignancy requires accumulation of multiple mutations
This classic colon cancer progression demonstrates that malignancy requires accumulation of multiple mutations affecting different pathways. While the precise temporal sequence may vary in different tumors, the principle of multistep carcinogenesis requiring several fundamental abnormalities is consistent.
Correct answer: A – 2 versus 36
Aerobic glycolysis (Warburg effect) produces only 2 ATP molecules per glucose molecule, versus 36 from mitochondrial oxidative phosphorylation. Despite being less efficient, this metabolic shift allows rapid cell division by shunting glucose carbons toward biosynthetic pathways.
Correct answer: B – PET scanning with 18F-fluorodeoxyglucose
The "glucose hunger" of tumors using aerobic glycolysis is exploited clinically through PET scanning, where patients receive 18F-fluorodeoxyglucose (a non-metabolizable glucose derivative). Rapidly growing tumors show marked PET-positivity due to high glucose uptake.
Correct answer: B – TP53, PTEN, and Akt
TP53, PTEN, and Akt (an intermediary in RAS signaling) stimulate glucose uptake by affecting glucose transporter proteins and favor aerobic glycolysis. This demonstrates that the Warburg effect becomes "hard-wired" through mutations in key regulatory genes.
Correct answer: B – Mismatch repair system
HNPCC patients have defects in the mismatch repair system, leading to microsatellite instability (MSI) characterized by changes in length of short tandem repeating sequences throughout the genome. This genomic instability increases colon cancer risk.
Correct answer: C – Homologous recombination repair
BRCA1 and BRCA2 are involved in homologous recombination DNA repair. Mutations in these genes impair the ability to repair double-strand DNA breaks, leading to genomic instability and increased breast and ovarian cancer risk.
Correct answer: A – Inability to repair pyrimidine dimers via nucleotide excision repair
Xeroderma pigmentosum patients have defects in the nucleotide excision repair pathway, making them unable to repair pyrimidine dimers caused by UV light. This leads to accumulation of mutations and dramatically increased risk of skin cancers in sun-exposed areas.
Correct answer: B – Secretion of reactive oxygen species causing DNA damage
Inflammatory cells like neutrophils contribute to carcinogenesis by secreting reactive oxygen species (ROS), which inflict DNA damage in rapidly dividing cells undergoing compensatory proliferation. This adds to the mutational burden during chronic tissue injury and repair.
Correct answer: B – Persistent cell replication during tissue repair increases mutation risk
Chronic inflammation from H. pylori causes compensatory proliferation during tissue repair. This persistent cell replication, aided by growth factors and cytokines from immune cells, places cells at risk of acquiring mutations in genes involved in carcinogenesis. Reduced apoptosis further compounds this risk.