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Open Access 01-06-2021 | Endometrial Cancer | Original Article

The immunologic tumor microenvironment in endometrioid endometrial cancer in the morphomolecular context: mutual correlations and prognostic impact depending on molecular alterations

Authors: Barbara Willvonseder, Fabian Stögbauer, Katja Steiger, Moritz Jesinghaus, Peer-Hendrik Kuhn, Christine Brambs, Jutta Engel, Holger Bronger, Georg Philipp Schmidt, Bernhard Haller, Wilko Weichert, Gisela Keller, Aurelia Noske, Nicole Pfarr, Melanie Boxberg

Published in: Cancer Immunology, Immunotherapy | Issue 6/2021

Abstract

Objective

POLE-mutant, microsatellite-instable (MSI), p53-mutant and non-specific molecular profile (NSMP) are TCGA-defined molecular subgroups of endometrial cancer (EC). Hypothesizing that morphology and tumor immunology might differ depending on molecular background concerning composition and prognostic impact, we aimed to comprehensively interconnect morphologic, immunologic and molecular data.

Methods

TCGA-defined molecular groups were determined by immunohistochemistry and sequencing in n = 142 endometrioid EC. WHO-defined histopathological grading was performed. The immunologic microenvironment (iTME) was characterised by the quantification of intraepithelial and stromal populations of tumor-infiltrating lymphocytes (TIL: overall T-cells; T-Killer cells; regulatory T-cells (Treg)). Immunologic parameters were correlated with WHO-grading, TCGA-subgroups and prognosis.

Results

High density TIL were significantly more frequent in high-grade (G3) compared to low-grade (G1/2) EC in the whole cohort and in the subgroup of POLE-wildtype-/microsatellite-stable-EC. MSI was associated with high-level TIL-infiltration when taking into account the type of mismatch repair defect (MLH1/PMS2; MSH2/MSH6). Prognostic impact of biomarkers depended on molecular subgroups: In p53-mutant EC, Treg were independently prognostic, in NSMP, the unique independently prognostic biomarker was WHO-grading.

Conclusions

EC morphology and immunology differ depending on genetics. Our study delineated two molecularly distinct subgroups of immunogenic EC characterized by high-density TIL-infiltration: MSI EC and high-grade POLE-wildtype/microsatellite-stable-EC. Prognostic impact of TIL-populations relied on TCGA-subgroups indicating specific roles for TIL depending on molecular background. In NSMP, histopathological grading was the only prognostic biomarker demonstrating the relevance of WHO-grading in an era of molecular subtyping.

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Title: The immunologic tumor microenvironment in endometrioid endometrial cancer in the morphomolecular context: mutual correlations and prognostic impact depending on molecular alterations
Authors: Barbara Willvonseder
Fabian Stögbauer
Katja Steiger
Moritz Jesinghaus
Peer-Hendrik Kuhn
Christine Brambs
Jutta Engel
Holger Bronger
Georg Philipp Schmidt
Bernhard Haller
Wilko Weichert
Gisela Keller
Aurelia Noske
Nicole Pfarr
Melanie Boxberg
Publication date: 01-06-2021
Publisher: Springer Berlin Heidelberg
Keywords: Endometrial Cancer
Endometrial Cancer
Published in: Cancer Immunology, Immunotherapy / Issue 6/2021
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-020-02813-3

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