Integrating pathology, chromosomal instability and mutations for risk stratification in early-stage endometrioid endomet
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Cell & Bioscience Open Access
RESEARCH
Integrating pathology, chromosomal instability and mutations for risk stratification in early‑stage endometrioid endometrial carcinoma Yuan Li1,2†, Jiaqi Li1†, Ensong Guo1,2, Jia Huang1,2, Guangguang Fang3, Shaohua Chen4, Bin Yang1,2, Yu Fu1,2, Fuxia Li1,2, Zizhuo Wang1,2, Rourou Xiao1,2, Chen Liu1,2, Yuhan Huang1,2, Xue Wu1,2, Funian Lu1,2, Lixin You1,2, Ling Feng1, Ling Xi1,2, Peng Wu1,2, Ding Ma1,2, Chaoyang Sun1,2*, Beibei Wang1,2* and Gang Chen1,2*
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: Endometrial carcinoma, Chromosomal instability, Histopathology, Molecular pathology, POLE, CTNNB1, Prognostic factor, Risk stratification
*Correspondence: [email protected]; [email protected]; [email protected] † Yuan Li and Jiaqi Li contribute equally to the paper 2 Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Anv, Wuhan 430030, Hubei, China Full list of author information is available at the end of the article
Background Endometrial carcinoma (EC) is the sixth most common malignant tumor in females worldwide and the second most common in the female reproductive system [1]. The risk stratification of EC is the prerequisite for the accurate evaluation of prognosis, and its ultimate goal is to improve the outcome of patients through the optimization of treatment guidelines. There
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