HER2 and GRB7 Expression in Serous and Endometrioid Carcinomas of the Endometrium
Claudia Velosa, Mark Bunker, Jan F Silverman, Uma Krishnamurti. West Penn Allegheny Health System, Pittsburgh
Background: Expression and amplification of HER2 is associated with high grade and stage endometrial cancer with the highest rate in serous carcinomas (20-80%) and the lowest in grade 1 endometrioid carcinomas (< 5%). Growth factor receptor-bound protein-7 (GRB7) gene located on chromosome 17 is in the immediate vicinity of the HER2 gene and promotes HER2 mediated signaling and tumor formation. The aim of this study was to evaluate HER2 and GRB7 expression in serous and endometrioid endometrial carcinomas.
Design: 53 cases of endometrial carcinoma from 2004 to 2010 were selected (31 cases of serous carcinoma (SC-58.5%) and 22 cases of endometrioid carcinoma (EC-41.5%). 5 of 22 cases of EC (16.1%) were grade 1 and 17 (83.8%) were grade 3. Immunohistochemical stains for HER2 and GRB7 were performed. HER2 was scored as: score 3 uniform intense membrane staining of > 30% of tumor cells; score 2 equivocal: complete membrane staining that is either non uniform or weak in intensity but with out obvious circumferential distribution in at least 10% of the cells; and score 0 or 1: negative: no staining or weak, incomplete membrane staining in any proportion cells. Scores 0 and 1 were considered negative, score 2 equivocal and score 3 positive. For GRB7 percentage of positively staining cells and intensity of staining were noted. < 10% cells with weak staining were considered negative.
Results: HER2 was positive in 13 of 31 (41.9%) of SC and equivocal in 4 cases (12.9%). GRB7 was expressed in 5 of 53 (9.4%)cases; all were SC of which 4 cases were HER2 positive and 1 case was HER2 equivocal. GRB7 positive cases showed > 30% cells with moderate to strong staining. Neither HER2 nor GRB7 expression was detected in EC. 5 of 22 EC (22.7%) were HER2 equivocal and the rest negative. 9 of the 13 HER2 positive (69.3%) SC were stage T3 or M1, one (7.7 %) case was T2 and 3 (23.0%) cases were T1. Of the 14 HER2 negative SC, 7 (50%) cases were T3, 2 (14.5%) cases were T2 and 5 (35.7%) were T1. 3 of 5 both HER2 and GRB7 positive SC were stage T3, the other two cases were stage T1 and T2.
Conclusions: Only SC showed overexpression of HER2 (41.9%) and GRB7 (6.0%) compared with EC (0.0%). Co-expression of HER2 and GRB7 was present in 30.7% cases of SC. Majority (69%) of HER2 positive SC presented as high stage (T3 or M1) cancers compared with HER2 negative SC (50%), although the differences were not statistically significant. Our findings suggest that there is a common biological pathway between HER2 and GRB7 in SC of the endometrium and that GRB7 in addition to HER2 could serve as target for therapy.
Category: Gynecologic & Obstetrics
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 179, Monday Morning