[1211] Histologic Effects of Short Term Progestin Therapy on Endometrioid Adenocarcinoma

RJ Zaino, WE Brady, W Todd, K Leslie, E Fischer, H Ball. Hershey Med Ctr, Hershey; GOG, Buffalo; U Iowa Med Ctr, Iowa City; UNM, Albuquerque; U Mass Med Ctr, Worcester

Background: Some recurrent endometrial carcinomas respond to hormonal therapy, but prediction of response is imperfect, its duration is usually short, and the mechanism is unknown. We wished to determine the efficacy of progestins to induce a histologic response in endometrioid carcinomas and explore its effects on immunohistochemical measures of growth and apoptosis.
Design: The Gynecologic Oncology Group initiated a study of 75 women with endometrioid endometrial adenocarcinoma, 60 of whom received medroxyprogesterone acetate for 21-24 days immediately prior to hysterectomy and have available slides. Initial biopsies and hysterectomies were H&E stained and immunostained for estrogen receptor (ER) and progesterone receptor (PR) (38 cases), Bcl-2, Mib-1, and cleaved caspase-3 (Casp3) (56 cases). Histologic response, including regression of characteristics of neoplasia, and presence of metaplasia, secretion, and decidual change was assessed, and semi-quantitative scores (0-3+) of immunohistologic variables of initial biopsies were compared to post treatment slides.
Results: Only 1 complete histologic response was seen, but 37 tumors had a partial response (more often in tumors of initial lower grade, p<0.05), reflected by increased eosinophilic cytoplasm and luminal secretion. Decidual change was sometimes prominent but limited to the stroma surrounding benign glands. About 90% of tumors were initially ER and PR positive. ER and PR were significantly down-regulated as was Mib-1. Although Bcl-2 decreased following therapy, Casp3 did not change significantly.

Table 1 immunohistochemical response

parameter	pre Rx (mean)	post Rx (mean)	significance
ER	2.25	1.62	p<0.05
PR	1.94	0.79	p<0.05
Mib-1 (nucl/HPF)	209	136	p<0.05
Bcl-2	0.60	0.24	p<0.05
Casp3	10.55	8.19	p=0.52

Conclusions: Short term progestin therapy induces partial histologic responses in most endometrioid adenocarcinomas, which is quantitatively and qualitatively different from that of benign endometrium. Based on observations at 21 days, the mechanism appears to reflect increased differentiation of tumor and a diminished growth rate rather than tumor cell death. Stromal decidulaization was confined to areas surrounding benign glands suggesting a paracrine effect. Down regulation of PR by the progestin may limit its efficacy and duration of response.
Category: Gynecologic & Obstetrics

Wednesday, March 24, 2010 9:30 AM

Poster Session V # 144, Wednesday Morning