ONCOPATHOLOGY MCQs - HALLMARKS OF CANCER | MCQ Quiz | OmpathStudy Kenya

Question 1

A patient with von Hippel-Lindau (VHL) syndrome develops multiple tumors. Which molecular mechanism BEST explains the increased angiogenesis in these tumors?

Accepted Answer

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.

Question 2

A tumor reaches 1.8 mm in diameter but fails to grow further for several years. Which statement BEST explains this phenomenon?

Accepted Answer

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.

Question 3

During tumor angiogenesis, MMP-9 performs multiple functions. Which combination of activities is CORRECT?

Accepted Answer

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.

Question 4

A researcher studies newly formed tumor vessels and compares them to normal capillaries. Which characteristic would MOST likely be observed in tumor vasculature?

Accepted Answer

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.

Question 5

Normal p53 plays a role in preventing angiogenesis. Which mechanism explains this anti-angiogenic effect?

Accepted Answer

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.

Question 6

Three angiogenesis inhibitors—angiostatin, endostatin, and vasculostatin—share what common characteristic?

Accepted Answer

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.

Question 7

Newly formed endothelial cells in tumor vessels contribute to tumor growth through which mechanism BEYOND providing nutrients?

Accepted Answer

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.

Question 8

A metastatic tumor cell must successfully complete multiple steps to establish a distant metastasis. At which stage do MOST tumor cells fail?

Accepted Answer

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.

Question 9

Loss of E-cadherin function promotes metastasis through which TWO mechanisms?

Accepted Answer

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.

Question 10

A breast cancer sample shows high expression of CXCR4 and CCR7 chemokine receptors. To which organs is this tumor MOST likely to metastasize?

Accepted Answer

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.

Question 11

During ECM invasion, tumor cells must complete four sequential steps. Which is the FIRST step?

Accepted Answer

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.

Question 12

Cleavage of basement membrane collagen IV and laminin by MMPs serves what additional purpose beyond degradation?

Accepted Answer

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.

Question 13

Why are skeletal muscles rarely sites of metastasis despite being well-vascularized?

Accepted Answer

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.

Question 14

Tumor-associated fibroblasts contribute to metastasis by exhibiting altered expression of multiple factors. Which combination is CORRECT?

Accepted Answer

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.

Question 15

Hepatocyte growth factor/scatter factor (HGF/SCF) is found at high concentrations at the advancing edges of glioblastoma multiforme. What is its primary role?

Accepted Answer

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.

Question 16

In the bloodstream, tumor cells that form emboli by aggregating with leukocytes and platelets gain what advantage?

Accepted Answer

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.

Question 17

A colon cancer shows the following sequence of mutations: APC inactivation → RAS activation → 18q loss → TP53 loss. This supports which concept?

Accepted Answer

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.

Question 18

Cancer cells exhibiting the Warburg effect produce how many ATP molecules per glucose compared to normal oxidative phosphorylation?

Accepted Answer

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.

Question 19

Rapidly growing tumors like Burkitt lymphoma utilize aerobic glycolysis despite its inefficiency. What clinical application exploits this metabolic characteristic?

Accepted Answer

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.

Question 20

Which oncogenes and tumor suppressors are now recognized to stimulate glucose uptake and favor aerobic glycolysis?

Accepted Answer

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.

Question 21

Patients with Hereditary Nonpolyposis Colon Cancer (HNPCC) have defects in which DNA repair system?

Accepted Answer

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.

Question 22

BRCA1 and BRCA2 genes, when mutated in familial breast cancers, normally function in which DNA repair pathway?

Accepted Answer

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.

Question 23

Patients with xeroderma pigmentosum have increased risk for UV-induced skin cancers due to defects in which repair mechanism?

Accepted Answer

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.

Question 24

Chronic inflammation promotes carcinogenesis through which mechanism involving neutrophils?

Accepted Answer

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.

Question 25

A patient with chronic H. pylori gastritis has increased cancer risk. Which factor MOST directly explains this association?

Accepted Answer

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.

Question 26

COX-2 inhibitors are being studied for cancer prevention. Which mechanism explains their potential benefit?

Accepted Answer

COX-2 produces prostaglandins in response to inflammatory stimuli — COX-2 expression is induced by inflammatory stimuli and converts arachidonic acid into prostaglandins. COX-2 is increased in colon and other cancers. Inhibiting COX-2 may reduce inflammation-mediated tumor promotion, making COX-2 inhibitors attractive for prevention.

Question 27

Recent gene expression profiling of breast cancers challenges traditional metastasis theory by suggesting:

Accepted Answer

Some tumors acquire metastatic capability early during carcinogenesis — Gene profiling shows some breast cancers have a metastasis-like signature early on, before clinical metastasis is apparent. This suggests that metastatic capability can be an intrinsic property developed during early carcinogenesis, not just from late-stage random mutations creating metastatic subclones.

Question 28

Normal epithelial cells undergo apoptosis when they lose attachment to basement membrane. Why are tumor cells resistant to this?

Accepted Answer

They are resistant to this form of cell death (anoikis) — Loss of adhesion in normal cells leads to induction of apoptosis (called anoikis), while tumor cells are resistant to this form of cell death. This resistance allows detached tumor cells to survive during invasion and metastasis, a critical capability for successful metastatic spread.

Question 29

Tumor cells that successfully colonize distant organs must interact with resident stromal cells. What do tumor cells secrete to make metastatic sites habitable?

Accepted Answer

Cytokines, growth factors, and proteases — Tumor cells secrete cytokines, growth factors, AND proteases that act on resident stromal cells. These stromal cells, in turn, make the metastatic site habitable for the cancer cell. This bidirectional communication is essential for successful colonization.

Question 30

In hypoxic tumor regions, what prevents HIF-1α from being degraded?

Accepted Answer

Lack of oxygen prevents HIF-1α recognition by VHL — In hypoxic conditions (like in tumors reaching critical size), lack of oxygen prevents HIF-1α recognition by VHL protein. Without VHL binding, HIF-1α is not ubiquitinated and degraded. Instead, it translocates to the nucleus and activates transcription of genes like VEGF, triggering angiogenesis.

ONCOPATHOLOGY MCQs - HALLMARKS OF CANCER | MCQ Quiz | OmpathStudy Kenya

Questions, Answers & Explanations