Journal
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
Volume 44, Issue 8, Pages 1104-1111Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/PAS.0000000000001519
Keywords
mixed endometrial carcinoma; endometrial carcinoma; molecular; mixed; immunohistochemistry; sequencing; pathology
Funding
- Translational Research Program at WCM Pathology and Laboratory Medicine
Ask authors/readers for more resources
Mixed endometrial carcinomas are defined as a combination of 2 or more distinct histologic subtypes, one of which must be a type II tumor comprising at least 5% of the tumor volume. The oncogenesis of these tumors remains unclear, particularly in light of the increasingly appreciated morphologic overlap among subtypes, as well as evolving molecular data. We evaluated 8 cases of mixed endometrial carcinoma, including 4 endometrioid (EC)/serous (SC), 1 SC/clear cell (CC), and 3 EC/CC cases, to study the underlying molecular features and oncogenic mechanisms at play. Each component was analyzed by a targeted next-generation sequencing assay. All tumors shared mutations in both components. In 6 cases, one component showed additional mutations. Two EC/SC cases showed shared mutations and mutations unique to each component. When present, unique mutations were typically seen in the SC component, including variants inPOLEandTP53, as well as potentially targetable genesDDR2,MAP2K1, andCCNE1. In EC/SC tumors,ERBB2abnormalities were seen in 2 cases. EC/CC cases showedFGFR2activating mutations in the EC component only. No fusion drivers were identified. Our data suggest that the majority of these tumors begin as a single clone and diverge along 2 pathways: (1) tumor progression, with one component showing additional mutations, and (2) tumor divergence, in which tumor components have both shared mutations and mutations unique to each component. In addition, the findings suggest a component of morphologic mimicry in these tumors. Our findings are clinically relevant since targetable mutations may be present in only one component of mixed tumors.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available