Differential Expression of Heart and Neural Crest Derivatives Expressed Transcript (HAND) 2 in Progesterone Treated Endometrium
Allison Cavallo, Rebecca Buell-Gutbrod, Anthony Montag, Nita Lee, Katja Gwin. University of Chicago, Chicago, IL
Background: Endometrioid (Type I) carcinomas (EMC) arise from an estrogen-dependent pathway. Progesterone inhibits estrogen-induced epithelial proliferation, is protective against endometrial hyperplasia and EMC, and is therapeutically used for these conditions. Expression of the progesterone induced heart and neural crest derivatives expressed transcript (HAND)2 has been shown to suppress production of fibroblast growth factors (FGFs), the mediators of the mitogenic effect of estrogen. In the presence of progesterone, HAND2 is upregulated and inhibits epithelial proliferation. We hypothesize that HAND2 mediated stromal epithelial-signaling plays a role in the pathogenesis of hyperplasia, EMC and in the therapeutic effect of progesterone.
Design: Archival paraffin embedded serial endometrial biopsies of 34 patients receiving progesterone were examined by IHC for expression of HAND2. Patients ranged in age from 20-66 years old. 16 patients received progesterone therapy via a hormone-releasing intrauterine device and 18 patients received intramuscular progesterone. Reasons for therapy included contraception (6/34), dysfunctional uterine bleeding (DUB) (9/34) and endometrial hyperplasia or EMC (19/34). HAND2 expression was scored as negative, weak, moderate or strong. Benign endometrium was used as a control.
Results: Of the patients with hyperplasia or EMC on initial biopsy, 32% progressed to or persisted with EMC, while the remaining 68% patients improved. HAND2 expression in the final specimen received from patients who progressed to EMC was negative in 5/6 of cases (83%), while HAND2 expression in patients who did not progress was either moderate or strong. Patients treated for DUB had strong HAND2 expression in 67% and moderate expression in 33%. All patients who received progesterone for contraception had moderate to strong HAND2 expression. Decidualization seen in response to progesterone effect always revealed moderate to strong HAND2 expression.
Conclusions: Despite the presence of exogenous progesterone in cases progressing to EMC, HAND2 was consistently not expressed. In contrast, HAND2 expression was maintained in cases responding to therapy, in areas of decidualization in response to progesterone, and in benign endometrium. These findings suggest that loss of HAND2 expression is an event in the progression of hyperplasia and EMC. The role of HAND2 in the stromal-epithelial signaling pathway may also explain why progesterone can be successfully used for the treatment of hyperplasia and selected EMC.
Category: Gynecologic & Obstetrics
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 172, Monday Morning