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Impact of endometrial carcinoma histotype on the prognostic value of the TCGA molecular subgroups

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Abstract

Background

The Cancer Genome Atlas (TCGA) identified four prognostic subgroups of endometrial carcinoma: copy-number-low/p53-wild-type (p53wt), POLE-mutated/ultramutated (POLEmt), microsatellite-instability/hypermutated (MSI), and copy-number-high/p53-mutated (p53mt). However, it is still unclear if they may be integrated with the current histopathological prognostic factors, such as histotype.

Objective

To assess the impact of histotype on the prognostic value of the TCGA molecular subgroups of endometrial carcinoma.

Methods

A systematic review and meta-analysis was performed by searching 7 electronic databases from their inception to April 2019 for studies assessing prognosis in all TCGA subgroups of endometrial carcinoma. Pooled hazard ratio (HR) for overall survival (OS) was calculated in two different groups (“all-histotypes” and “endometrioid”), using p53wt subgroup as reference standard; HR for non-endometrioid histotypes was calculated indirectly. Disease-specific survival and progression-free survival were assessed as additional analyses.

Results

Six studies with 2818 patients were included. In the p53mt subgroup, pooled HRs for OS were 4.322 (all-histotypes), 2.505 (endometrioid), and 4.937 (non-endometrioid). In the MSI subgroup, pooled HRs were 1.965 (all-histotypes), 1.287 (endometrioid), and 6.361 (non-endometrioid). In the POLEmt subgroup, pooled HRs were 0.763 (all-histotypes), 0.481 (endometrioid), and 2.634 (non-endometrioid). Results of additional analyses were consistent for all subgroups except for non-endometrioid POLEmt carcinomas.

Conclusion

Histotype of endometrial carcinoma shows a crucial prognostic value independently of the TCGA molecular subgroup, with non-endometrioid carcinomas having a worse prognosis in each TCGA subgroup. Histotype should be integrated with molecular characterization for the risk stratification of patients in the future.

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Funding

No financial support was received for this study.

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Authors and Affiliations

  1. Anatomic Pathology Unit, Department of Advanced Biomedical Sciences, School of Medicine, University of Naples Federico II, Naples, Italy

    Antonio Travaglino, Paola Moretta & Luigi Insabato

  2. Gynecology and Obstetrics Unit, Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Via Sergio Pansini, 5, 80131, Naples, Italy

    Antonio Raffone, Cristina Stradella, Rosanna Esposito, Giuliana Orlandi & Fulvio Zullo

  3. Gynecology and Obstetrics Unit, Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, Catanzaro, Italy

    Cinzia Gallo

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  1. Antonio Travaglino
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Contributions

AT and AR independently assessed electronic search, eligibility of the studies, inclusion criteria, risk of bias, data extraction, and data analysis. CS, RE, PM, CG, and GO contributed to the elaboration of methods for risk of bias assessment, data extraction, and analysis. AT, AR, LI, and FZ conceived the study; AT, AR, CS, LI, and FZ worked on the design of the study; AT, AR, RE, PM, and CG worked on the manuscript preparation; LI and FZ supervised the whole study.

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Correspondence to Antonio Raffone.

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404_2020_5542_MOESM1_ESM.tif

Flow diagram of studies identified in the systematic review (Prisma template [Preferred Reporting Item for Systematic Reviews and Meta-analyses]). (TIFF 19 kb)

404_2020_5542_MOESM2_ESM.tif

Risk of bias within studies. Upper graph: Summary of risk of bias for each study; Plus sign: low risk of bias; minus sign: high risk of bias; question mark: unclear risk of bias. Lower graph: Risk of bias graph about each risk of bias item presented as percentages across all included studies (TIFF 22 kb)

404_2020_5542_MOESM3_ESM.tif

Forest plots of hazard ratio (HR) for disease-specific survival in the TCGA molecular subgroups of endometrial carcinoma (“all-histotypes” group) (TIFF 203 kb)

404_2020_5542_MOESM4_ESM.tif

Forest plots of hazard ratio (HR) for progression-free survival in the TCGA molecular subgroups of endometrial carcinoma (“all-histotypes” group) (TIFF 204 kb)

404_2020_5542_MOESM5_ESM.tif

Forest plots of hazard ratio (HR) for disease-specific survival in the TCGA molecular subgroups of endometrial carcinoma (“endometrioid” group) (TIFF 155 kb)

404_2020_5542_MOESM6_ESM.tif

Forest plots of hazard ratio (HR) for progression-free survival in the TCGA molecular subgroups of endometrial carcinoma (“endometrioid” group) (TIFF 182 kb)

404_2020_5542_MOESM7_ESM.tif

Scale of hazard ratio for disease-specific survival (DSS) in the TCGA subgroups of endometrial carcinoma stratified by histotype: endometrioid (pink squares), non-endometrioid (blue squares) or all histotypes (no squares) (TIFF 65 kb)

404_2020_5542_MOESM8_ESM.tif

Scale of hazard ratio for progression-free survival (PFS) in the TCGA subgroups of endometrial carcinoma stratified by histotype: endometrioid (pink squares), non-endometrioid (blue squares) or all histotypes (no squares) (TIFF 66 kb)

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Travaglino, A., Raffone, A., Stradella, C. et al. Impact of endometrial carcinoma histotype on the prognostic value of the TCGA molecular subgroups. Arch Gynecol Obstet 301, 1355–1363 (2020). https://doi.org/10.1007/s00404-020-05542-1

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