Oncopathology Hallmarks of Cancer MCQs

Question 1

A 45-year-old woman with VHL syndrome develops multiple tumors. Which molecular mechanism explains the angiogenic phenotype in her renal cell carcinomas?

Accepted Answer

Failure of HIF-1α ubiquitination in normoxic conditions — In VHL syndrome, mutated VHL protein cannot bind and ubiquitinate HIF-1α even in normoxic conditions, leading to constitutive HIF-1α stabilization and VEGF transcription, promoting angiogenesis. ---

Question 2

What is the maximum diameter a tumor can reach without developing its own vascular supply?

Accepted Answer

1-2 mm — Tumors cannot enlarge beyond 1-2 mm in diameter without angiogenesis due to the maximal diffusion distance for oxygen, nutrients, and waste from blood vessels. ---

Question 3

A researcher studying tumor angiogenesis finds that proteolytic cleavage of plasminogen produces a potent angiogenesis inhibitor. Which molecule is formed?

Accepted Answer

Angiostatin — Angiostatin is produced by proteolytic cleavage of plasminogen. Endostatin comes from collagen cleavage, and vasculostatin from transthyretin cleavage. ---

Question 4

Which cell adhesion molecule acts as both an intercellular glue and transmits antigrowth signals by sequestering β-catenin?

Accepted Answer

E-cadherin — E-cadherin functions as an intercellular adhesion molecule and transmits antigrowth signals by sequestering β-catenin. Its function is lost in almost all epithelial cancers. ---

Question 5

A patient with hereditary nonpolyposis colon cancer (HNPCC) develops multiple colonic carcinomas. Which genetic finding characterizes this syndrome?

Accepted Answer

Mismatch repair defects with microsatellite instability — HNPCC is caused by defects in mismatch repair genes, leading to microsatellite instability (MSI) characterized by changes in length of short tandem repeating sequences throughout the genome. ---

Question 6

Normal p53 induces synthesis of which angiogenesis inhibitor?

Accepted Answer

Thrombospondin-1 (TSP-1) — Normal p53 induces synthesis of TSP-1, the prototypical angiogenesis inhibitor, maintaining vascular quiescence in early tumor growth. ---

Question 7

Which enzyme is responsible for cleaving type IV collagen in basement membranes and releasing VEGF from ECM-sequestered pools?

Accepted Answer

MMP-9 — MMP-9 is a gelatinase that cleaves type IV collagen of epithelial and vascular basement membranes and stimulates release of VEGF from ECM-sequestered pools. ---

Question 8

A patient with xeroderma pigmentosum develops multiple skin cancers after minimal sun exposure. Which DNA repair pathway is defective?

Accepted Answer

Nucleotide excision repair — Xeroderma pigmentosum involves defects in nucleotide excision repair, leading to inability to repair UV-induced pyrimidine dimers and increased risk of skin cancers. ---

Question 9

Which transcription factors suppress E-cadherin expression, promoting tumor cell invasion?

Accepted Answer

SNAIL and TWIST — SNAIL and TWIST transcription factors suppress E-cadherin expression, leading to loss of intercellular adhesion and promoting tumor cell invasion and metastasis. ---

Question 10

In the Warburg effect, how many ATP molecules are produced per glucose molecule through aerobic glycolysis?

Question 11

Which imaging modality exploits the Warburg effect to visualize tumors using 18F-fluorodeoxyglucose?

Accepted Answer

PET scan — PET scanning uses 18F-fluorodeoxyglucose, a nonmetabolizable glucose derivative, to visualize the increased glucose uptake characteristic of tumors exhibiting the Warburg effect. ---

Question 12

What is the dual effect of neovascularization on tumor growth?

Accepted Answer

Perfusion supplies nutrients AND newly formed endothelial cells secrete growth factors — Neovascularization has a dual effect: perfusion supplies oxygen and nutrients, while newly formed endothelial cells stimulate tumor growth by secreting growth factors like IGF, PDGF, and GM-CSF. ---

Question 13

A breast cancer patient's tumor shows high expression of CXCR4 and CCR7 receptors. To which organs is this tumor most likely to metastasize based on chemokine ligand expression?

Accepted Answer

Organs expressing CXCL12 and CCL21 — Breast cancer cells expressing CXCR4 and CCR7 metastasize to organs highly expressing their ligands (CXCL12 and CCL21), demonstrating organ tropism through chemokine receptor-ligand interactions. ---

Question 14

Which DNA repair genes are mutated in familial breast cancers and are involved in homologous recombination?

Accepted Answer

BRCA1 and BRCA2 — BRCA1 and BRCA2 are involved in DNA repair through homologous recombination and are mutated in familial breast cancers, increasing cancer susceptibility. ---

Question 15

In hypoxic conditions within a tumor, what prevents HIF-1α degradation?

Accepted Answer

Lack of oxygen prevents VHL recognition of HIF-1α — In hypoxia, lack of oxygen prevents VHL from recognizing and binding HIF-1α, preventing its ubiquitination and degradation, allowing HIF-1α to translocate to the nucleus and activate VEGF transcription. ---

Question 16

Which of the following best describes the first step in ECM invasion by tumor cells?

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, before cells can invade the ECM. ---

Question 17

What happens to normal epithelial cells when they lose adhesion to the ECM?

Accepted Answer

They undergo apoptosis — Loss of adhesion in normal cells leads to induction of apoptosis, while tumor cells are resistant to this form of cell death, allowing them to survive during metastasis. ---

Question 18

Which syndrome is characterized by hypersensitivity to ionizing radiation due to defects in homologous recombination DNA repair?

Accepted Answer

Ataxia-telangiectasia — Ataxia-telangiectasia involves defects in homologous recombination DNA repair and is characterized by hypersensitivity to DNA-damaging agents like ionizing radiation. ---

Question 19

In the multistep carcinogenesis model of colon cancer, which genetic alteration typically occurs FIRST?

Accepted Answer

Inactivation of APC — In colon carcinogenesis, inactivation of the APC tumor suppressor gene typically occurs first, followed by RAS activation, then loss of chromosome 18q, and finally loss of TP53. ---

Question 20

What is the primary reason skeletal muscles are rarely sites of metastasis despite being well vascularized?

Accepted Answer

Nonpermissive microenvironment — Although well vascularized, skeletal muscles provide a nonpermissive microenvironment for tumor cell growth, demonstrating that vascularization alone is insufficient for metastasis. ---

Question 21

Which growth factor/cytokine is secreted by tumor cells to promote their own locomotion in an autocrine manner?

Accepted Answer

Autocrine motility factors — Tumor cells secrete autocrine motility factors that act on themselves to potentiate and direct migration through degraded basement membranes and matrix zones during invasion. ---

Question 22

What is the role of tumor-associated fibroblasts in the tumor microenvironment?

Accepted Answer

They exhibit altered gene expression that can promote tumorigenesis — Tumor-associated fibroblasts exhibit altered expression of genes encoding ECM molecules, proteases, protease inhibitors, and growth factors, actively participating in creating a microenvironment that can promote tumorigenesis. ---

Question 23

In normoxic conditions, what happens to HIF-1α?

Accepted Answer

It is bound by VHL, ubiquitinated, and destroyed — In normoxic settings, VHL protein binds to HIF-1α, leading to its ubiquitination and subsequent destruction, preventing inappropriate angiogenesis activation. ---

Question 24

Which enzyme cleaves collagen to produce endostatin, a potent angiogenesis inhibitor?

Accepted Answer

Proteases acting on collagen — Endostatin is produced by proteolytic cleavage of collagen by various proteases, serving as one of the potent angiogenesis inhibitors that balance pro-angiogenic signals. ---

Question 25

What characterizes tumor vasculature compared to normal vessels?

Accepted Answer

Leaky, dilated with haphazard connections — Tumor vasculature is abnormal, characterized by leaky, dilated vessels with haphazard patterns of connection, unlike the organized structure of normal blood vessels. ---

Question 26

Which mechanism do aggregated tumor cells in the bloodstream use to avoid immune destruction?

Accepted Answer

Adhesion to leukocytes and platelets forming emboli — Tumor cells form emboli by aggregating and adhering to circulating leukocytes and platelets, affording them protection from antitumor host effector cells during circulation. ---

Question 27

What is the significance of the "angiogenic switch" in tumor development?

Accepted Answer

It terminates the stage of vascular quiescence allowing tumor progression — The angiogenic switch terminates the stage of vascular quiescence, allowing tumors that were small or in situ for years to progress by acquiring blood supply through increased angiogenic factors and/or loss of inhibitors. ---

Question 28

Which chronic inflammatory condition of the gastrointestinal tract increases cancer risk through persistent cell proliferation and DNA damage?

Accepted Answer

Ulcerative colitis — Ulcerative colitis increases cancer risk through chronic inflammation causing compensatory proliferation and DNA damage. ---

Question 29

How do inflammatory cells like neutrophils contribute to carcinogenesis?

Accepted Answer

By secreting reactive oxygen species causing DNA damage — Neutrophils and other inflammatory cells contribute to carcinogenesis by secreting reactive oxygen species (ROS), which inflict DNA damage in rapidly dividing cells during chronic inflammation. ---

Question 30

Which enzyme's increased expression in colon cancers has led to research on its inhibitors for cancer prevention?

Accepted Answer

Cyclooxygenase-2 (COX-2) — COX-2 expression is increased in colon cancers and other tumors. It converts arachidonic acid to prostaglandins and is induced by inflammatory stimuli, making COX-2 inhibitors a target for cancer prevention research. ---

Question 31

What finding challenges the traditional theory that metastasis results from random mutation accumulation in tumor subclones?

Accepted Answer

Some primary tumors have gene expression signatures similar to metastases before clinical metastasis — Gene profiling studies show some breast cancers have metastasis-like gene expression signatures in primary tumors before clinical metastasis, suggesting metastatic potential may be an early intrinsic property. ---

Question 32

Which paracrine factor produced by stromal cells binds to receptors on tumor cells to promote motility?

Accepted Answer

Hepatocyte growth factor/scatter factor (HGF/SCF) — HGF/SCF is a paracrine effector of cell motility produced by stromal cells. It binds to receptors on tumor cells and is elevated at advancing edges of invasive tumors. ---

Question 33

Benign tumors of the breast show little activity of which enzyme compared to their malignant counterparts?

Accepted Answer

Type IV collagenase (MMP activity) — Benign tumors show little type IV collagenase activity, whereas their malignant counterparts overexpress this enzyme, which is crucial for basement membrane degradation. ---

Question 34

What is the consequence of MMP-mediated cleavage of basement membrane proteins like collagen IV and laminin?

Accepted Answer

Generation of novel binding sites that stimulate tumor cell migration — MMP-2 and MMP-9 cleavage of collagen IV and laminin generates novel sites that bind to receptors on tumor cells and stimulate migration. ---

Question 35

Which oncogenes and tumor suppressors stimulate glucose uptake and favor aerobic glycolysis in cancer cells?

Accepted Answer

TP53, PTEN, and Akt — TP53, PTEN, and Akt stimulate glucose uptake by affecting glucose transporter proteins and favor aerobic glycolysis (the Warburg effect). ---

Question 36

In the invasion-metastasis cascade, which step must occur before intravasation?

Accepted Answer

Local invasion — The invasion-metastasis cascade follows a specific sequence: local invasion must occur before tumor cells can intravasate into blood and lymph vessels. ---

Question 37

What is the primary function of integrins on normal epithelial cells in relation to the basement membrane?

Accepted Answer

Act as polarized receptors maintaining cells in resting, differentiated state — Normal epithelial cells have integrins at their basal surface for basement membrane components that help maintain cells in a resting, differentiated state. ---

Question 38

Which cleavage products of matrix components have chemotactic activity for tumor cells?

Accepted Answer

Collagen and laminin fragments — Cleavage products of collagen and laminin, along with certain growth factors like IGF-I and IGF-II, have chemotactic activity that directs tumor cell migration. ---

Question 39

What typically happens to the levels of metalloproteinase inhibitors in malignant tumors?

Accepted Answer

They are reduced, tilting balance toward tissue degradation — In malignant tumors, levels of metalloproteinase inhibitors are typically reduced, tilting the balance toward tissue degradation and facilitating invasion.

Oncopathology Hallmarks of Cancer MCQs

Questions, Answers & Explanations