Integrating pathology, chromosomal instability and mutations for risk stratification in early-stage endometrioid endometrial carcinoma

Yuan Li; Jiaqi Li; Ensong Guo; Jia Huang; Guangguang Fang; Shaohua Chen; Bin Yang; Yu Fu; Fuxia Li; Zizhuo Wang; Rourou Xiao; Chen Liu; Yuhan Huang; Xue Wu; Funian Lu; Lixin You; Ling Feng; Ling Xi; Peng Wu; Ding Ma; Chaoyang Sun; Beibei Wang; Gang Chen

doi:10.1186/s13578-020-00486-0

Integrating pathology, chromosomal instability and mutations for risk stratification in early-stage endometrioid endometrial carcinoma

Cell Biosci. 2020 Oct 22:10:122. doi: 10.1186/s13578-020-00486-0. eCollection 2020.

Authors

Yuan Li^#^{1

2}, Jiaqi Li^#¹, Ensong Guo^{1

2}, Jia Huang^{1

2}, Guangguang Fang³, Shaohua Chen⁴, Bin Yang^{1

2}, Yu Fu^{1

2}, Fuxia Li^{1

2}, Zizhuo Wang^{1

2}, Rourou Xiao^{1

2}, Chen Liu^{1

2}, Yuhan Huang^{1

2}, Xue Wu^{1

2}, Funian Lu^{1

2}, Lixin You^{1

2}, Ling Feng¹, Ling Xi^{1

2}, Peng Wu^{1

2}, Ding Ma^{1

2}, Chaoyang Sun^{1

2}, Beibei Wang^{1

2}, Gang Chen^{1

2}

Affiliations

¹ National Clinical Research Center of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Anv, Wuhan, 430030 Hubei China.
³ Department of Gynecology,Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen Dapeng New District Maternity & Child Health Hospital, Shenzhen, 518038 China.
⁴ Department of Gynecology and Obstetrics, The People's Hospital of Macheng City, Macheng, 438300 China.

^# Contributed equally.

Abstract

Background: Risk stratifications for endometrial carcinoma (EC) depend on histopathology and molecular pathology. Histopathological risk stratification lacks reproducibility, neglects heterogeneity and contributes little to surgical procedures. Existing molecular stratification is useless in patients with specific pathological or molecular characteristics and cannot guide postoperative adjuvant radiotherapies. Chromosomal instability (CIN), the numerical and structural alterations of chromosomes resulting from ongoing errors of chromosome segregation, is an intrinsic biological mechanism for the evolution of different prognostic factors of histopathology and molecular pathology and may be applicable to the risk stratification of EC.

Results: By analyzing CIN25 and CIN70, two reliable gene expression signatures for CIN, we found that EC with unfavorable prognostic factors of histopathology or molecular pathology had serious CIN. However, the POLE mutant, as a favorable prognostic factor, had elevated CIN signatures, and the CTNNB1 mutant, as an unfavorable prognostic factor, had decreased CIN signatures. Only if these two mutations were excluded were CIN signatures strongly prognostic for outcomes in different adjuvant radiotherapy subgroups. Integrating pathology, CIN signatures and POLE/CTNNB1 mutation stratified stageIendometrioid EC into four groups with improved risk prognostication and treatment recommendations.

Conclusions: We revealed the possibility of integrating histopathology and molecular pathology by CIN for risk stratification in early-stage EC. Our integrated risk model deserves further improvement and validation.

Keywords: CTNNB1; Chromosomal instability; Endometrial carcinoma; Histopathology; Molecular pathology; POLE; Prognostic factor; Risk stratification.