Endometrial Carcinomas with a "Serous" Component in Young Women Are Enriched for DNA Mismatch Repair Deficiency, Lynch Syndrome, and POLE Exonuclease Domain Mutations.
Am J Surg Pathol
; 44(5): 641-648, 2020 05.
Article
en En
| MEDLINE
| ID: mdl-32205482
ABSTRACT
Endometrial carcinoma (EC), as described by Bokhman, has historically been classified as Type I (low-grade, hormone-dependant, young patients, good prognosis) or Type II (high-grade, hormone-independent, older patients, poor prognosis). This classification is no longer pragmatic, however, as EC is a much more heterogeneous disease. Four molecular subtypes of EC were identified by The Cancer Genome Atlas (TCGA), and subsequent studies have demonstrated its utility in predicting prognosis. While endometrial serous carcinoma (ESC), the prototypical Type II EC, largely occurs in older women, younger women with ESC were not accounted for in the Bokhman model and were underrepresented in the TCGA study. We hypothesized that a subset of ESCs in young patients do not represent bona fide serous carcinomas but rather high-grade endometrioid carcinomas mimicking a serous phenotype. We identified ESCs and mixed endometrioid/serous carcinomas in women <60 years (n=37), and analyzed their clinical, morphologic, immunohistochemical, and molecular characteristics. Sixteen percent showed mismatch repair deficiency (MMR-D) and 11% were diagnosed with Lynch syndrome. Additionally, 16% of cases tested harbored a hotspot POLE exonuclease domain mutation (POLE-EDM). Morphologically, 47% of tumors showed confirmatory endometrioid features, including atypical hyperplasia, a low-grade endometrioid carcinoma component, or squamous differentiation. Clinically, the overall survival in patients with MMR-D and POLE-EDM was significantly better than that of patients without these features (P=0.0329). In conclusion, ESCs in young patients comprise a heterogeneous group of tumors, demonstrating diverse clinical, immunohistochemical, morphologic, and molecular features which have implications for prognosis and adjuvant therapy.
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Bases de datos:
MEDLINE
Asunto principal:
Neoplasias Colorrectales Hereditarias sin Poliposis
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Biomarcadores de Tumor
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Neoplasias Endometriales
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Neoplasias Quísticas, Mucinosas y Serosas
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Neoplasias Complejas y Mixtas
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Enzimas Reparadoras del ADN
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ADN Polimerasa II
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Reparación de la Incompatibilidad de ADN
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Proteínas de Unión a Poli-ADP-Ribosa
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Mutación
Tipo de estudio:
Etiology_studies
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Prognostic_studies
Límite:
Adult
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Female
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Humans
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Middle aged
Idioma:
En
Revista:
Am J Surg Pathol
Año:
2020
Tipo del documento:
Article