Mutational profile of endometrial hyperplasia and risk of progression to endometrioid adenocarcinoma

Abstract

BACKGROUND: Endometrial hyperplasia is a precursor to endometrioid adenocarcinoma (EMC), the most common uterine cancer. The likelihood of progression to carcinoma may be evaluated by histologic subclassification of endometrial hyperplasia, although these subclasses are subjective and only modestly reproducible among pathologists. Patient care would be improved by a more objective test to predict the risk of cancer progression. METHODS: Next-generation sequencing was performed on archived endometrial biopsy specimens from a retrospective cohort of women with endometrial hyperplasia. Cases were considered to be either progressing if the patient subsequently developed EMC or resolving if the patient had a subsequent negative tissue sampling or no cancer during medium-term follow-up (32 patients: 15 progressing and 17 resolving). Somatic mutations in endometrial hyperplasia were assessed for enrichment in progressing cases versus resolving cases, with an emphasis on genes commonly mutated in EMC. RESULTS: Several mutations were more common in progressing hyperplasia than resolving hyperplasia, although significant overlap was observed between progressing and resolving cases. Mutations included those in PTEN, PIK3CA, and FGFR2, genes commonly mutated in EMC. Mutations in ARID1A and MYC were seen only in progressing hyperplasia, although these were uncommon; this limited diagnostic sensitivity. Progressing hyperplasia demonstrated an accumulation of mutations in oncogenic signaling pathways similarly to endometrial carcinoma. CONCLUSIONS: Because of mutational differences between progressing and nonprogressing hyperplasia, mutational analysis may predict the risk of progression from endometrial hyperplasia to EMC. Cancer 2020;126:2775-2783.

Hormone autocrination by vascularized hydrogel delivery of ovary spheroids to rescue ovarian dysfunctions

“…The hormone treatment groups (OVX + E and OVX + E + P) significantly increased the hyperplasia area and number compared to the OVX group, whereas the OVX + VHOS group maintained normal levels comparable to that of the OVX-intact group. Because endometrial hyperplasia is considered a potential inducer of uterine cancer ( 29 , 30 ), expression of cancer markers (p53 and PTEN) was examined by immunohistochemistry (IHC) and Western blot ( Fig. 5B ).…”

Next-generation sequencing analysis of endometrial screening liquid-based cytology specimens: a comparative study to tissue specimens

“…In the present study, we did not analyze AH/EIN cases. Since a significant overlap of gene mutations is reported between AH, EIN, and EC [45,46], a combination study with cytology and pathology would further improve the diagnostic accuracy.…”

Application of immunocytochemical and molecular analysis of six genes in liquid‐based endometrial cytology

“…Recently, many genes have been reported to have relation with endometrial carcinoma . [7][8][9][10][11][12][13][14][15][16][17][18][19] Application of ancillary techniques on cytology to search such a gene expression and gene mutation is expected to expand the power of cytology. Therefore, aberrant gene expression and/or gene mutation analysis was applied in addition to conventional cytology in this study.…”