PTEN Status and Frequency of Endometrioid Carcinoma and Its Precursors Arising in Functional Secretory Endometrium: An Immunohistochemical Study of 29 Cases
Rochelle A Simon, Katrine Hansen, Jinjun Xiong, C James Sung, W Dwayne Lawrence, M Ruhul Quddus. Brown University/Women & Infants Hospital, Providence, RI
Background: Well-differentiated (WD) endometrioid adenocarcinoma (EMCA) and its precursors, complex hyperplasia without atypia and atypical hyperplasia (endometrial intraepithelial neoplasia, EIN), often arise in a background of proliferative, but particularly anovulatory, endometrium secondary to prolonged unopposed hyperestrinism. Although endometrial hyperplasia or EMCA is not typically associated with functional secretory endometrium, the frequency of such lesions has, to our knowledge, not been described in the literature. Mutations of the PTEN tumor suppressor gene may occur in up to 80% of EMCA and 2/3 of EIN, resulting in loss of immunohistochemical expression of PTEN. However, the PTEN status of typical EMCA and its precursors arising in physiologic secretory endometrium has not been reported, and forms the basis for our study.
Design: From our institutional archives we identified 29 endometrial biopsy, curettage, or hysterectomy specimens, over 8 ½ years, showing EMCA and/or endometrial hyperplasia arising in physiologic secretory endometrium. We reviewed routine H&E slides of these cases to confirm the diagnoses for PTEN immunohistochemistry (Cascade Bioscience; 1:100 dilution). PTEN-null cases were defined by an absence of immunostain within the lesional glands.
Results: A total of 1601 cases of endometrial carcinoma and 528 cases of atypical endometrial hyperplasia were identified over the study period. Twenty-nine cases of endometrial hyperplasia or carcinoma arising in secretory endometrium were identified in patients 37-54 yrs of age (median: 44 yrs). Diagnoses included 7 complex hyperplasia without cytologic atypia (CH), 9 atypical complex hyperplasia (ACH), 11 FIGO grade 1 EMCA, one FIGO grade 2 EMCA, and 2 tumors of mixed cell type (serous and WD endometrioid). Twenty-one of 29 cases had tissue available for immunostaining. PTEN-null lesions were identified in 1 of 6 (16.7%) cases of CH, 5 of 5 (100%) cases of ACH, and 7 of 8 (87.5%) cases of grade 1 EMCA. The WD endometrioid component of one mixed cell type tumor was PTEN-null, while the grade 2 EMCA was PTEN-positive.
Conclusions: Our findings confirm that typical EMCA and its precursor lesions only rarely arise within a functioning secretory endometrium (frequency of <2% in our study). We found the rate of PTEN-null cases of these lesions to be comparable to that of the usual type reported in the literature. Loss of PTEN expression was noted more frequently in atypical hyperplasia or low grade carcinoma than in non-atypical hyperplasia or grade 2 EMCA.
Category: Gynecologic & Obstetrics
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 131, Tuesday Afternoon