A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Grade and Estrogen Receptor Expression Identify a Subset of No Specific Molecular Profile Endometrial Carcinomas at a Very Low Risk of Disease- Specific Death
Tekijät: Jamieson Amy, Huvila Jutta, Chiu Derek, Thompson Emily F, Scott Stephanie, Salvador Shannon, Vicus Danielle, Helpman Limor, Gotlieb Walter, Kean Sarah, Samouelian Vanessa, Köbel Martin, Kinloch Mary, Parra-Harran Carlos, Offman Saul, Grondin Katherine, Irving Julie, Lum Amy, Senz Janine, Leung Samuel, McConechy Melissa K, Plante Marie, Kommoss Stefan, Huntsman David G, Talhouk Aline, Gilks C Blake, McAlpine Jessica N
Kustantaja: ELSEVIER SCIENCE INC
Julkaisuvuosi: 2023
Journal: Modern Pathology
Tietokannassa oleva lehden nimi: MODERN PATHOLOGY
Lehden akronyymi: MODERN PATHOL
Artikkelin numero: 100085
Vuosikerta: 36
Numero: 4
Sivujen määrä: 12
ISSN: 0893-3952
DOI: https://doi.org/10.1016/j.modpat.2022.100085
Endometrial carcinoma (EC) can be divided into 4 prognostic molecular subtypes, and no specific molecular profile (NSMP) type is the most commonly occurring type (similar to 50%). Although described as having an intermediate to favorable prognosis, this subtype encompasses pathologically and molecularly diverse tumors. We aimed to identify factors associated with outcomes within the NSMP ECs that might be used to stratify prognosis and direct treatment. Clinicopathologic, immu-nohistochemical, and genetic features of a large series of NSMP EC were used to identify parameters that could identify the subset associated with a very favorable outcome (disease-specific death rate <5% at 5 years, termed low-risk NSMP). A total of 1110 NSMP ECs were profiled. In a univariate analysis, stage, grade, lymphovascular invasion, estrogen receptor (ER) and progesterone receptor (PR) expression, L1CAM overexpression, and mutations in PIK3CA were associated with disease -specific survival. Two critical features, grade and ER expression, identified a low-risk NSMP subset (grade 1-2, ER-positive [>1%], 84% of cases), which showed a 5-year disease-specific death rate of 1.6% across all stages and 1.4% within stage I. The remaining cases (high-risk NSMPs, grade 3, and/or ER-negative status) were responsible for most of the disease-specific deaths (disease-specific death rate at 5 years, 22.9%; hazard ratio compared with that of low-risk NSMPs: 16.3; 95% CI, 8.4-31.7). Within NSMP EC, the low-risk and high-risk categories were of prognostic significance independent of the stage on a multivariate analysis. Low-grade and ER-positive NSMP ECs are a homogeneous low-risk group associated with an exceptionally favorable prognosis in which de-escalation and/or endocrine therapy strategies can be applied. Grade 3 and/or ER-negative status identifies a high-risk NSMP subset, including rare high-grade histotypes (eg, clear cell, dedifferentiated, and mesonephric-like), responsible for most NSMP-related deaths. Subclassification of NSMPs allows for the category of low-risk EC molecular subtypes to be dramatically expanded because it now includes both POLEmut and the much more common low-risk NSMP EC. (c) 2022 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.
