Neoplasia USMLE Step 1 Practice Question
A 67-year-old man with a 10-year history of Barrett esophagus presents to the gastroenterology clinic with progressive dysphagia to solids and unintentional weight loss of 8 kg over 3 months. He reports chronic heartburn managed with intermittent antacids. Vital signs are stable. Upper endoscopy reveals a 3-cm ulcerated lesion in the distal esophagus. Biopsy of the lesion shows adenocarcinoma with adjacent areas of columnar metaplasia containing intestinal-type mucosa and high-grade dysplasia. Immunohistochemical staining demonstrates loss of p53 and SMAD4 protein expression. Which of the following best explains the molecular progression from Barrett esophagus to invasive adenocarcinoma in this patient?
Answer choices
- ALoss of APC tumor suppressor and activation of Wnt/β-catenin signaling
- BInactivation of BRCA1/BRCA2 genes leading to homologous recombination repair deficiency
- CInactivation of TP53 and disruption of TGF-β/SMAD signalingCorrect answer
- DActivation of KRAS with concurrent loss of CDKN2A/p16 function
- EMismatch repair gene deficiency causing microsatellite instability and Lynch syndrome
- FHPV E6/E7 oncoprotein expression with inactivation of RB pathway
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