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Emerging relationships between papillary proliferation of the endometrium and endometrial carcinoma: evidence from an immunohistochemical and molecular analysis

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Papillary proliferation of the endometrium (PPE) is an uncommon lesion that frequently shows mucinous metaplasia. PPE occasionally has concurrent or preceding endometrial hyperplasia and carcinomas, but there is little molecular evidence to support the relationships between PPEs and endometrial neoplasia. In this study, we analyzed the clinicopathological and immunohistochemical features in 30 PPEs (22 simple PPEs and 8 complex papillary hyperplasia (CPH)). Hotspot mutations of KRAS, PI3KCA, AKT1, PTEN (exons 3, 5, and 7), and ARID1A (exons 1 and 14) were detected by pyrosequencing or bidirectional Sanger sequencing. We found that endometrial hyperplasia and carcinoma were more common in CPHs (4/6, 66.7%) than in simple PPEs (4/21, 19.0%) (p < 0.05). Compared with the adjacent normal endometrium, PPEs frequently showed loss of PAX2 (56.7%) and PTEN (10%) expression, diffuse p16 expression (36.7%), decreased PR expression (84.3%), and lower Ki67 labeling index (median 1%, range 1–15%). Simple PPEs and CPHs had similar immunohistochemical features (p > 0.05). KRAS mutations were identified in 14 PPEs and 1 concurrent endometrial carcinoma. The prevalence of KRAS mutations was not statistically different between simple PPEs (10/21, 45.5%) and CPHs (4/8, 50%) (p > 0.05), but was higher in PPEs displaying mucinous metaplasia (12/24, 50%) than in those without (2/6, 33.3%) (p < 0.05). One simple PPE with a KRAS mutation had an AKT1 mutation. No PPEs demonstrated mutations in PI3KCA, PTEN, and ARID1A. In conclusion, both simple PPE and CPH share some common molecular alterations with endometrial neoplasia, in which, KRAS mutations might be a driver.

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We also thank Mrs. Caiyun Zhou, Department of Surgical Pathology, Women’s Hospital, School of Medicine, Zhejiang University, and Dr. Yanfeng Bai, Department of Pathology & Pathophysiology, School of Medicine, Zhejiang University, for their excellent technical support.


This work is supported by grants from Department of Health, Zhejiang Province, China [2013KYB149], Zhejiang Health and Family Planning Commission, China [JSW2013-A013], and Natural Science Foundation of China [81202067].

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LQ, Wu Q, YM, and LB researched and analyzed data, and wrote the manuscript. SH and LB edited and reviewed the manuscript. LB conceived and designed the study. All authors gave final approval for publication. LB takes full responsibility for the work as a whole, including the study design, access to data, and the decision to submit and publish the manuscript.

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Correspondence to Bingjian Lu.

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This study was conducted with the approval of the Institutional Review Board of Women’s Hospital, School of Medicine, Zhejiang University (IRB 20170135).

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The authors declare that they have no conflict of interest.

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Liu, Q., Wu, Q., Yu, M. et al. Emerging relationships between papillary proliferation of the endometrium and endometrial carcinoma: evidence from an immunohistochemical and molecular analysis. Virchows Arch 475, 201–209 (2019).

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