A 55-year-old obese woman with a history of polycystic ovary syndrome and unopposed estrogen use for 5 years is diagnosed with well-differentiated endometrioid endometrial carcinoma. Which molecular feature is MOST commonly associated with this hormone-driven (Type 1) endometrial carcinoma?

• A TP53 mutation
• B HER2 amplification
• C POLE mutation with ultramutated phenotype
• D PTEN inactivation ✓

Explanation

Type 1 endometrial carcinoma (endometrioid, estrogen-driven, well-differentiated) most commonly shows PTEN tumor suppressor gene inactivation, which is found in approximately 83% of cases—the earliest and most frequent molecular alteration. PTEN loss leads to activation of the PI3K-AKT-mTOR pathway, promoting cell proliferation. TP53 mutations are characteristically associated with Type 2 (non-endometrioid, serous, high-grade, estrogen-independent) endometrial carcinoma. POLE mutations define an ultra-mutated subtype with paradoxically excellent prognosis.

Reference: Shaw's Textbook of Gynaecology, 17th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.