Clinical application of TCGA molecular classification in endometrial endometrioid carcinoma
10.3760/cma.j.issn.0529-5807.2019.08.003
- VernacularTitle: 癌症基因组图谱子宫内膜癌分子分型在子宫内膜样癌中的临床应用探索
- Author:
Ningning DU
1
;
Yan LIU
1
;
Caixia REN
2
;
Yuxiang WANG
1
;
Juan DU
1
;
Jing YANG
1
;
Congrong LIU
1
Author Information
1. Department of Pathology, School of Basic Medical Sciences, Peking University Third Hospital, Peking University Health Science Center, Beijing 100191, China
2. Department of Human Anatomy, Histology and Embryology, Peking University Health Science Center, Beijing 100191, China
- Publication Type:Journal Article
- Keywords:
Carcinoma, endometrioid;
Molecular typing;
Pathology, clinical;
Prognosis
- From:
Chinese Journal of Pathology
2019;48(8):596-603
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore molecular characteristics of endometrial endometrioid cancer according to The Cancer Genome Atlas (TCGA) based molecular classification of endometrial carcinomas and to confirm simple and clinically applicable surrogate methodologies in pathological practice.
Methods:Two hundred and twenty-eight cases of endometrial endometroid adenocarcinomas (EnACs) collected from August 2001 to August 2017 from Peking University Health Science Center, Peking University Third Hospital were molecularly categorized by using Sanger sequencing for the exonuclease domain mutations (EDM) of POLE, and by immunohistochemistry for p53 and mismatch repair (MMR) proteins. The cohort was classified into polymerase-E exonuclease domain mutation (POLE EDM), mismatch repair deficiency (MMR-D), p53 abnormal (p53-abn) and p53 wild type (p53-wt) groups. The correlation between molecular subgroups and the clinical-pathological features including prognosis were analyzed.
Results:The cohort was distributed as follows: 11(4.8%) POLE EDM, 47(20.6%) MMR-D, 9(4.0%) p53-abn and 161(70.6%) p53-wt. p53-wt subgroup patients demonstrated significantly higher lymph node metastasis (P=0.011) and more advanced stage (P=0.036) than those of somatic hypermutation group cases (POLE EDM and MMR-D). In the FIGO grade 2-3 EnACs cohort, TCGA molecular subtyping was significantly correlated with progression-free survival and overall survival (P=0.043). POLE EDM subgroup had the best survival, while p53-abn subgroup had the worst.
Conclusions:Identification of POLE EDM and MMR-D subgroups provides independent and highly valuable prognostic information beyond established histological classification. Based on immunohistochemistry of MMR, p53 and POLE mutational analysis, this pragmatic molecular classification scheme can be served as a reliable surrogate for TCGA molecular classification, which has potential to be used routinely in Chinese pathological practice.
