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Endometrial cancer with a POLE mutation progresses frequently through the type I pathway despite its high-grade endometrioid morphology: a cohort study at a single institution in Japan

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Abstract

POLE-mutated endometrial cancer (EC) frequently shows high-grade endometrioid histology, which represents heterogeneity in the dualistic classification of EC. This study aimed to assess the clinicopathology and pathogenesis of POLE-mutated EC due to the scarcity of related information for Asian women. POLE variants were sequenced in tissues of Japanese women with EC. The tumor mutation burden (TMB) was assessed in tissues with a POLE variant of unknown significance. In the POLE-mutated EC tissues, the immunostaining expression of CD8, hormonal receptors, and p53 was evaluated, and the POLE variants in cancer and atypical endometrial hyperplasia (AEH) lesions were assessed by laser-capture microdissection. POLE variants were identified in five patients (3.9%) with high-grade endometrioid carcinoma among 127 patients with EC (S459F in two tissues and P441P in three tissues with a high TMB). The five cancer tissues coexisted with normal endometrium and/or AEH. Both AEH and cancer cells showed hormonal receptor positivity and harbored the same POLE mutation. Two patients showed a subclonal overexpression pattern of p53 in cancer and AEH lesions. In conclusion, POLE-mutated EC progresses through the type I pathway, even though it frequently shows high-grade endometrioid morphology. The common POLE mutation sites in EC might vary among races.

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Acknowledgements

The authors would like to thank Ms. Takako Keida (Division of Genomics, Institute of Resource Development and Analysis, Kumamoto University) for the technical assistance provided with the sequencing analysis.

Funding

The present study was supported by JSPS KAKENHI (Grant Numbers JP16K11145 and JP18K16806).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan

    Mahina Monsur, Munekage Yamaguchi, Fumitaka Saito, Chimeddulam Erdenebaatar, Chenyan Li, Yutaka Iwagoi, Takashi Ohba & Hidetaka Katabuchi

  2. Department of Woman’s Health Sciences and Pediatric Nursing, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan

    Hironori Tashiro

  3. Division of Genomics, Institute of Resource Development and Analysis, Kumamoto University, Kumamoto, Japan

    Kumiko Yoshinobu

  4. Department of Surgical Pathology, Kumamoto General Hospital, Japan Community Health Care Organization, Kumamoto, Japan

    Ken-ichi Iyama

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  1. Mahina Monsur
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Correspondence to Munekage Yamaguchi.

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795_2020_273_MOESM2_ESM.pptx

Supplementary file2 Supplementary figure 1: Immunostaining for MLH1, MSH2, PMS2, and MSH6 in endometrial cancer in patient 2. Positive expression of all MMR proteins, including MLH1 (A), MSH2 (B), PMS2 (C), and MSH6 (D), was found. (magnification, ×100) (PPTX 1083 KB)

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Monsur, M., Yamaguchi, M., Tashiro, H. et al. Endometrial cancer with a POLE mutation progresses frequently through the type I pathway despite its high-grade endometrioid morphology: a cohort study at a single institution in Japan. Med Mol Morphol 54, 133–145 (2021). https://doi.org/10.1007/s00795-020-00273-3

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