title: Stromal p16 expression is significantly increased in endometrial carcinoma.
abstract: p16 is a negative regulator of cell proliferation and is considered a tumor suppressor protein. Alterations in p16 protein expression are associated with tumor development and progression. However, the p16 expression status in the peritumoral stroma has not been investigated in the endometrium. Therefore, we evaluated stromal p16 expression in different types of endometrial lesions using immunohistochemistry. Differences in the p16 expression status according to the degree of malignancy and histological type were analyzed. This study included 62, 26, and 36 cases of benign, precancerous, and malignant endometrial lesions, respectively. Most benign lesions showed negative or weak expression, whereas precancerous lesions showed a variable degree of staining proportion and intensity. Atypical hyperplasia/endometrial intraepithelial neoplasia (AH/EIN) and serous endometrial intraepithelial carcinoma (SEIC) had significantly higher stromal p16 expression levels than benign lesions. Endometrioid carcinoma (EC), serous carcinoma (SC), and carcinosarcoma showed significantly elevated stromal p16 expression levels compared with benign and precancerous lesions. In addition, there were significant differences in stromal p16 expression between AH/EIN and SEIC and between EC and SC. In contrast, differences in stromal p16 expression among nonpathological endometrium, atrophic endometrium, endometrial polyp, and hyperplasia without atypia were not statistically significant. Our observations suggest that stromal p16 expression is involved in the development and progression of endometrial carcinoma, and raise the possibility that p16 overexpression in the peritumoral stroma is associated with aggressive oncogenic behavior of endometrial SC.
authors.affiliation: Shinsegae Women's Hospital, Daegu, Republic of Korea.
authors.forename: Gun
authors.initials: G
authors.lastname: Yoon
authors.affiliation: Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Chang Won
authors.initials: CW
authors.lastname: Koh
authors.affiliation: Department of Pathology, The Catholic University of Korea Incheon St. Mary's Hospital, Incheon, Republic of Korea.
authors.forename: Nara
authors.initials: N
authors.lastname: Yoon
authors.affiliation: Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Ji-Ye
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hyun-Soo
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D018269:Carcinoma, Endometrioid / Q000378:metabolism; D002296:Carcinosarcoma / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism; D004714:Endometrial Hyperplasia / Q000378:metabolism* / Q000473:pathology; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16
keywords: endometrioid carcinoma; endometrium; p16; peritumoral stroma; serous carcinoma