A 58-year-old postmenopausal woman presents with postmenopausal bleeding. Endometrial biopsy shows endometrioid adenocarcinoma, Grade 2. Regarding the prognostic and molecular features of her tumor, all of the following are associated with favorable prognosis EXCEPT:

Explanation

## Endometrial Carcinoma: Prognostic Factors and Molecular Markers ### Favorable vs Unfavorable Prognostic Features | Feature | Favorable | Unfavorable | |---------|-----------|-------------| | **Stage** | IA–IB (confined to uterus) | III–IV (extrauterine spread) | | **Grade** | 1–2 (well to moderately differentiated) | 3 (poorly differentiated) | | **Myometrial invasion** | <50% or superficial | ≥50% (deep invasion) | | **LVSI** | Absent | Present | | **Molecular profile** | PTEN, KRAS mutations (Type I) | TP53 mutations (Type II) | | **MSI status** | MSI-high (better in Type I) | MSI-low or MSS (Type II worse) | | **p53 expression** | Wild-type (low/absent) | Mutant (high/abnormal) | **Key Point:** p53 mutations and high p53 protein expression are hallmarks of Type II (serous/aggressive) carcinomas and are associated with **worse** prognosis, not favorable. ### Molecular Classification (TCGA/PORTEC-4a) **High-Yield:** Modern endometrial cancer prognostication uses four molecular subtypes: 1. **POLE-mutated**: Best prognosis (even if high-grade) 2. **MSI-high (mismatch repair deficient)**: Intermediate prognosis; responsive to immunotherapy 3. **p53 wild-type (PTEN/KRAS mutations)**: Type I, favorable prognosis 4. **p53 mutant**: Type II, worst prognosis **Clinical Pearl:** High p53 protein on IHC (indicating TP53 mutation) is a marker of Type II carcinoma and predicts aggressive behavior, recurrence, and poor survival — it is an **unfavorable** prognostic sign, not favorable. ### Why Option 3 Is Incorrect High p53 expression (abnormal/mutant pattern) on immunohistochemistry reflects TP53 mutations and is associated with Type II carcinoma, which carries a significantly worse prognosis. This is an **unfavorable** prognostic feature. The question asks for the option that is NOT associated with favorable prognosis — Option 3 fits this criterion. ### Favorable Features in This Case - **Option 0**: PTEN mutations + MSI-low = Type I molecular signature, favorable - **Option 1**: FIGO Stage IA with <50% myometrial invasion = early-stage, favorable - **Option 3**: Absent LVSI + low mitotic activity = favorable histological features [cite:Robbins 10e Ch 22]