医学
免疫组织化学
增生
腺癌
子宫内膜癌
异型性
子宫内膜
非典型腺瘤性增生
上皮内瘤变
原位癌
作者
Mariano Russo,James R. Broach,Kathryn Sheldon,Kenneth R. Houser,Dajiang J. Liu,Joshua Kesterson,Rebecca Phaeton,Carrie Hossler,Nadine Hempel,Maria J. Baker,Jordan M. Newell,Richard J. Zaino,Joshua I. Warrick
标识
DOI:10.1016/j.humpath.2017.07.003
摘要
Endometrial intraepithelial neoplasia (EIN) and atypical endometrial hyperplasia (AH) are histomorphologically defined precursors to adenocarcinoma, which are unified as EIN/AH by the World Health Organization. EIN/AH harbors a constellation of molecular alterations similar to those found in adenocarcinoma. However, the process of clonal evolution from EIN/AH to carcinoma is poorly characterized. To investigate, we performed next-generation sequencing, number alteration (CNA) analysis, and immunohistochemistry for mismatch repair protein expression on EIN/AH and adenocarcinoma samples from 6 hysterectomy cases with spatially distinct EIN/AH and carcinoma. In evaluating all samples, EIN/AH and carcinoma did not differ in mutational burden, CNA burden, or specific genes mutated (all P>.1). All paired EIN/AH and carcinoma samples shared at least one identical somatic mutation, frequently in PI(3)K pathway members. Large CNAs (>10 genes in length) were identified in 83% of cases; paired EIN/AH and carcinoma samples shared at least one identical CNA in these cases. Mismatch repair protein expression matched in all paired EIN/AH and carcinoma samples. All paired EIN/AH and carcinoma samples had identical The Cancer Genome Atlas subtype, with 3 classified as copy number low endometrioid and 3 classified as microsatellite instability hypermutated. Although paired EIN/AH and carcinoma samples were clonal, private mutations (ie, present in only one sample) were identified in EIN/AH and carcinoma in all cases, frequently in established cancer-driving genes. These findings indicate that EIN/AH gives rise to adenocarcinoma by a complex process of subclone evolution, not a linear accumulation of molecular events.
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