Abstract
BackgroundRisk 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.ResultsBy 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.ConclusionsWe 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.
Highlights
Risk stratifications for endometrial carcinoma (EC) depend on histopathology and molecular pathology
Relationships between Chromosomal instability (CIN) and prognostic factors of histopathology in EC To investigate the CIN reflected by CIN signatures in EC, we first confirmed the difference in CIN signatures between benign and malignant endometria
Overall, except for POLE and CTNNB1 mutations, serious CIN represented by increased CIN25 and CIN70 are characteristic of unfavorable prognostic factors in EC
Summary
Risk stratifications for endometrial carcinoma (EC) depend on histopathology and molecular pathology. Li et al Cell Biosci (2020) 10:122 two kinds of stratification systems, conventional pathology assignment in the guidelines and emerging molecular classification proposed by The Cancer Genome Atlas (TCGA) [2, 3] In the former system, prognostic factors of histopathology, such as histopathological type, grade, stage, myometrial invasion (MI) and lymphovascular space invasion (LVSI), constitute indications for risk assessment and adjuvant radiotherapy [2]. The lack of consensus among pathologists on the histopathological type and tumor grade assignment has resulted in the same woman receiving different classifications, treatments, and clinical outcomes [4] In addition to this poor reproducibility of prognostic factors, tremendous diversity in clinical outcomes of patients with the same clinicopathological features suggests that the heterogeneity of EC is ignored in this traditional system [5]. Since most of the prognostic factors of histopathology used for risk stratification are only available after surgery, such as MI and LVSI, this risk model contributes little to decisions regarding surgical procedures
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