Genetic features of endometrioid-type endometrial carcinoma arising in uterine adenomyosis

This study aimed to clarify the genetic features of endometrioid-type endometrial cancer arising in adenomyosis (EC-AIA) using targeted sequencing and immunohistochemistry (IHC) for both carcinoma and adjacent adenomyosis tissues. We identified three endometrioid-type EC-AIAs in 689 patients with endometrial cancer; two exhibited grade 3 endometrioid carcinoma. IHC revealed retained expression of PMS2, MSH6, ARID1A, and PAX2. Two of them showed diffuse strong p53 expression only in the carcinoma. PTEN expression was lost in carcinoma of only one of these cases. Carcinoma had many gene mutations than adjacent adenomyosis in all cases. KRAS and TP53 mutations were found in two of them. The other patient had mutations in KRAS, PIK3CA, and PPP2R1A. They were classified as two "p53-mutated" and one "non-specific molecular profile." These molecular alterations in endometrioid-type EC-AIA imply similar carcinogenesis to a subset of endometrial endometrioid carcinoma and might be used as targets of liquid biopsy after further validation.

本研究旨在通过对癌组织及邻近子宫腺肌病组织进行靶向测序和免疫组化（IHC），明确子宫腺肌病相关的子宫内膜样型子宫内膜癌（EC - AIA）的遗传学特征。我们在689例子宫内膜癌患者中确定了3例子宫内膜样型EC - AIA；其中2例为3级子宫内膜样癌。免疫组化显示PMS2、MSH6、ARID1A和PAX2保留表达。其中2例仅在癌组织中呈现弥漫性强p53表达。仅其中1例的癌组织中PTEN表达缺失。在所有病例中，癌组织比邻近的子宫腺肌病组织有更多的基因突变。其中2例发现KRAS和TP53突变。另1例患者存在KRAS、PIK3CA和PPP2R1A突变。它们被归类为2例“p53突变型”和1例“非特异性分子特征”。子宫内膜样型EC - AIA中的这些分子改变意味着其致癌机制与一部分子宫内膜样型子宫内膜癌相似，经过进一步验证后可能用作液体活检的靶点。