Oncopathology Hallmarks of Cancer MCQs – 39 MCQs | Kenya MBChB

39 Year 3: General Pathology exam questions on Oncopathology Hallmarks of Cancer MCQs for medical students. Includes MCQs, answers, explanations and written que

This MCQ set contains 39 questions on Oncopathology Hallmarks of Cancer MCQs in the Year 3: General Pathology unit. Each question includes the correct answer and a detailed explanation for active recall and exam preparation.

Q1: A 45-year-old woman with VHL syndrome develops multiple tumors. Which molecular mechanism explains the angiogenic phenotype in her renal cell carcinomas?

  1. A. Increased TSP-1 production
  2. B. Enhanced VHL-mediated HIF-1α degradation
  3. C. Failure of HIF-1α ubiquitination in normoxic conditions
  4. D. Decreased VEGF receptor expression

Correct answer: C – 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.

Q2: What is the maximum diameter a tumor can reach without developing its own vascular supply?

  1. A. 0.5-1 mm
  2. B. 1-2 mm
  3. C. 3-4 mm
  4. D. 5-6 mm

Correct answer: B – 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.

Q3: A researcher studying tumor angiogenesis finds that proteolytic cleavage of plasminogen produces a potent angiogenesis inhibitor. Which molecule is formed?

  1. A. Endostatin
  2. B. Vasculostatin
  3. C. Angiostatin
  4. D. Thrombospondin-1

Correct answer: C – Angiostatin

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

Q4: Which cell adhesion molecule acts as both an intercellular glue and transmits antigrowth signals by sequestering β-catenin?

  1. A. N-cadherin
  2. B. E-cadherin
  3. C. Integrin
  4. D. L-selectin

Correct answer: B – 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.

Q5: A patient with hereditary nonpolyposis colon cancer (HNPCC) develops multiple colonic carcinomas. Which genetic finding characterizes this syndrome?

  1. A. Nucleotide excision repair defects
  2. B. Homologous recombination defects
  3. C. Mismatch repair defects with microsatellite instability
  4. D. Base excision repair defects

Correct answer: C – 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.

Q6: Normal p53 induces synthesis of which angiogenesis inhibitor?

  1. A. VEGF
  2. B. Thrombospondin-1 (TSP-1)
  3. C. Angiostatin
  4. D. Endostatin

Correct answer: B – Thrombospondin-1 (TSP-1)

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

Q7: Which enzyme is responsible for cleaving type IV collagen in basement membranes and releasing VEGF from ECM-sequestered pools?

  1. A. MMP-2
  2. B. Cathepsin D
  3. C. MMP-9
  4. D. Urokinase plasminogen activator

Correct answer: C – 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.

Q8: A patient with xeroderma pigmentosum develops multiple skin cancers after minimal sun exposure. Which DNA repair pathway is defective?

  1. A. Mismatch repair
  2. B. Nucleotide excision repair
  3. C. Base excision repair
  4. D. Homologous recombination

Correct answer: B – 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.

Q9: Which transcription factors suppress E-cadherin expression, promoting tumor cell invasion?

  1. A. p53 and PTEN
  2. B. HIF-1α and VHL
  3. C. SNAIL and TWIST
  4. D. RAS and AKT

Correct answer: C – 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.

Q10: In the Warburg effect, how many ATP molecules are produced per glucose molecule through aerobic glycolysis?

  1. A. 2
  2. B. 4
  3. C. 18
  4. D. 36

Correct answer: A – 2

Aerobic glycolysis produces only 2 ATP molecules per glucose molecule, compared to 36 ATP from mitochondrial oxidative phosphorylation, yet supports rapid tumor growth.

Q11: Which imaging modality exploits the Warburg effect to visualize tumors using 18F-fluorodeoxyglucose?

  1. A. MRI
  2. B. CT scan
  3. C. PET scan
  4. D. Ultrasound

Correct answer: C – PET scan

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

Q12: What is the dual effect of neovascularization on tumor growth?

  1. A. Perfusion supplies nutrients AND newly formed endothelial cells secrete growth factors
  2. B. Increases oxygen delivery AND removes immune cells
  3. C. Decreases apoptosis AND increases metastasis
  4. D. Enhances drug delivery AND reduces hypoxia

Correct answer: A – 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.

Q13: 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?

  1. A. Skin and muscle
  2. B. Organs expressing CXCL12 and CCL21
  3. C. Spleen and thymus only
  4. D. Brain and kidneys only

Correct answer: B – 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.

Q14: Which DNA repair genes are mutated in familial breast cancers and are involved in homologous recombination?

  1. A. MLH1 and MSH2
  2. B. BRCA1 and BRCA2
  3. C. XPA and XPC
  4. D. PTEN and TP53

Correct answer: B – BRCA1 and BRCA2

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

Q15: In hypoxic conditions within a tumor, what prevents HIF-1α degradation?

  1. A. Increased VHL binding
  2. B. Enhanced ubiquitination
  3. C. Lack of oxygen prevents VHL recognition of HIF-1α
  4. D. Decreased HIF-1α production

Correct answer: C – 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.

Q16: Which of the following best describes the first step in ECM invasion by tumor cells?

  1. A. Degradation of basement membrane
  2. B. Locomotion through matrix
  3. C. Loosening of tumor cell-to-cell contacts
  4. D. Attachment to ECM proteins

Correct answer: C – 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.

Q17: What happens to normal epithelial cells when they lose adhesion to the ECM?

  1. A. They proliferate rapidly
  2. B. They undergo apoptosis
  3. C. They become immortalized
  4. D. They differentiate

Correct answer: B – 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.

Q18: Which syndrome is characterized by hypersensitivity to ionizing radiation due to defects in homologous recombination DNA repair?

  1. A. Lynch syndrome
  2. B. Xeroderma pigmentosum
  3. C. Ataxia-telangiectasia
  4. D. Li-Fraumeni syndrome

Correct answer: C – Ataxia-telangiectasia

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

Q19: In the multistep carcinogenesis model of colon cancer, which genetic alteration typically occurs FIRST?

  1. A. Loss of TP53
  2. B. Activation of RAS
  3. C. Inactivation of APC
  4. D. Loss of chromosome 18q

Correct answer: C – 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.

Q20: What is the primary reason skeletal muscles are rarely sites of metastasis despite being well vascularized?

  1. A. High blood flow
  2. B. Nonpermissive microenvironment
  3. C. Lack of chemokine receptors
  4. D. Strong immune surveillance

Correct answer: B – Nonpermissive microenvironment

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

Q21: Which growth factor/cytokine is secreted by tumor cells to promote their own locomotion in an autocrine manner?

  1. A. VEGF
  2. B. Autocrine motility factors
  3. C. TSP-1
  4. D. E-cadherin

Correct answer: B – 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.

Q22: What is the role of tumor-associated fibroblasts in the tumor microenvironment?

  1. A. They only present a static barrier to tumor cells
  2. B. They exhibit altered gene expression that can promote tumorigenesis
  3. C. They exclusively inhibit tumor growth
  4. D. They have no interaction with tumor cells

Correct answer: B – 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.

Q23: In normoxic conditions, what happens to HIF-1α?

  1. A. It accumulates in the nucleus
  2. B. It is bound by VHL, ubiquitinated, and destroyed
  3. C. It activates VEGF transcription
  4. D. It inhibits angiogenesis

Correct answer: B – 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.

Q24: Which enzyme cleaves collagen to produce endostatin, a potent angiogenesis inhibitor?

  1. A. MMP-2
  2. B. Proteases acting on collagen
  3. C. Cathepsin D
  4. D. Urokinase

Correct answer: B – 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.

Q25: What characterizes tumor vasculature compared to normal vessels?

  1. A. Regular, organized pattern
  2. B. Leaky, dilated with haphazard connections
  3. C. Decreased permeability
  4. D. Absence of endothelial cells

Correct answer: B – 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.

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