THE USMLE TIMES - #96
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Welcome to issue #96 of The USMLE Times… This is the 96th straight week we’ve posted our USMLE Times Newsletter! Thank you to all of our supporters—new and old! As we cruise to our 100th issue, we’re getting ready to make a significant announcement about the future of The USMLE Guys—stay tuned!
I’m Paul Ciurysek, MD, and this is The USMLE Times: An independent, subscriber-supported newsletter designed to help you survive medical school, pass your USMLE exams, and match into your dream residency program. All content is FREE for 48 hours… If you’d like unlimited, lifetime access to everything (plus bonus access to our drills books), consider becoming a Premium Subscriber.
Here’s what’s on tap for issue #96 of the USMLE Times:
Question of the Week (GI pathology)
This week’s video training (Acid-Base Tutorial)
Question deep-dive & breakdown
Free subscribers have access for 48 hours after the post goes live.
Let’s dive in!
A 62-year-old male presents to the clinic with a 6-month history of worsening epigastric pain, early satiety, and unintentional weight loss of 20 lbs. He reports a history of smoking for thirty years and consuming alcohol regularly. His family history is notable for a father who was diagnosed with gastric cancer at the age of sixty-five years. His vital signs are as follows: Blood pressure 135/85 mmHg, pulse 88/minute, respirations 17/minute, and temperature 98.4°F (36.9°C). Laboratory studies show:
Hemoglobin: 9.8 g/dL (N: 13.5-17.5 g/dL)
Mean corpuscular volume (MCV): 82 fL
Serum iron: 45 mcg/dL (N: 65-175 ug/dL)
Ferritin: 25 ng/mL (N: 20-250 ng/mL)
An upper endoscopy reveals a large ulcerative lesion in the gastric antrum. Histopathological examination of the tissue biopsy confirms a diagnosis of gastric adenocarcinoma. Which of the following molecular markers is most likely to be overexpressed?
A. HER2
B. EGFR
C. BRAF
D. KRAS
E. PD-L1
F. MET
G. PIK3CA
The answer & question breakdown is at the bottom of the post 👇🏼
🔗 LINKS TO RECENT POSTS
USMLE Times Issue #95 - READ HERE
USMLE Practice Question #70 - TRY IT HERE
USMLE Practice Question #69 - TRY IT HERE
This week’s recommended video 👇🏼
ANSWER + QUESTION BREAKDOWN
The mental model used to answer this question comes from our detailed test-taking skills masterclass. Here’s how to think through this question:
Step 1. Read the last line to determine the question: “Which of the following molecular markers is most likely to be overexpressed?”
Step 2. Determine if this is a first-, second-, or third-order question. It is 2nd order. 1st: Diagnose the problem, 2nd: Identify the correct molecular marker.
Step 3. Ask yourself: “Which marker do I expect to find in this condition?”
Step 4. Look at the answer choices and select the option most closely resembling your thoughts from “Step 3” above.
GENERAL ANALYSIS
The clinical presentation and biopsy findings of the 62-year-old male patient are consistent with gastric adenocarcinoma. In the context of gastric cancer, certain molecular markers are known to be overexpressed, which can have implications for prognosis and treatment.
ANSWER CHOICES:
ANSWER CHOICE A: HER2
Explanation: HER2 (Human Epidermal Growth Factor Receptor 2) is a well-known marker that can be overexpressed in gastric cancer. It is part of the EGFR family and is associated with aggressive tumor behavior. HER2 overexpression is observed in a subset of gastric adenocarcinomas, particularly the intestinal type, making it a relevant marker for this case.
ANSWER CHOICE B: EGFR
Explanation: EGFR (Epidermal Growth Factor Receptor) is another member of the receptor tyrosine kinase family involved in cell proliferation. While EGFR can be involved in gastric cancer, HER2 is more specifically associated with certain subtypes of gastric adenocarcinoma.
ANSWER CHOICE C: BRAF
Explanation: BRAF mutations are commonly associated with melanoma and some colorectal cancers but are not typically associated with gastric adenocarcinoma.
ANSWER CHOICE D: KRAS
Explanation: KRAS mutations are often found in colorectal cancer and pancreatic cancer but are not typically associated with gastric adenocarcinoma.
ANSWER CHOICE E: PD-L1
Explanation: PD-L1 expression is related to immune checkpoint pathways and can be relevant for immunotherapy decisions. While it can be expressed in gastric cancer, it is not as directly associated as HER2 for this context.
ANSWER CHOICE F: MET
Explanation: MET amplification can occur in various cancers, including gastric cancer. However, HER2 is a more established marker for gastric adenocarcinoma.
ANSWER CHOICE G: PIK3CA
Explanation: PIK3CA mutations occur in various cancers but are not specifically highlighted in gastric adenocarcinoma.
THE VERDICT…
HER2 overexpression is a significant molecular marker in gastric adenocarcinoma, particularly in the intestinal subtype. It has implications for targeted therapies, such as trastuzumab, which are used in HER2-positive cases. The presence of HER2 overexpression can guide treatment decisions and provide prognostic information.
FINAL ANSWER: A. HER2
That’s it for issue #96 of The USMLE Times!
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