Abstract 362: Comparison of Mig-6 and hormone receptor expression to BMI as predictors of responsiveness to progestin therapy for endometrial hyperplasia and cancer

Abstract

Abstract Objectives: Mitogen-inducible gene 6 (Mig-6) is an immediate early response gene that can be induced by stressful stimuli and mitogens, including hormones and growth factors. Ablation of Mig-6 leads to epithelial hyperplasia and adenocarcinomas in a variety of organs, including the endometrium. Mig-6 has been identified as a downstream target of the progesterone receptor (PR) in the uterus. Thus, our goal was to compare Mig-6 and hormone receptor expression to BMI as predictors of responsiveness to progestin therapy for endometrial hyperplasia and cancer. Methods: Women were identified who underwent progestin treatment (oral or IUD) for either endometrial hyperplasia or cancer. Expression of Mig-6 and the hormone receptors, G-protein coupled receptor 30 (GPR30), estrogen receptor (ER) and PR were evaluated by immunohistochemistry (IHC) in 58 paired formalin-fixed, paraffin-embedded endometrial biopsy specimens before and after progestin treatment. Tissue microarrays were constructed, and three cores were analyzed for each patient. IHC staining was scored according to the intensity (1+ to 3+) and qualitative percent cells staining per core. A “histoscore” was calculated, based on multiplying these two determinants ranging from 0 to 300 (i.e. intensity x % labeled). Results were analyzed using the Student t-test and ANOVA. Results: There were 41 responders to progestin therapy and 17 non-responders. The majority had endometrial hyperplasia (56/58) but 2 women had grade I endometrial carcinomas. The BMI between the two groups was statistically different at 40.2 for the responders and 49.9 for the non-responders (p=0.0008). There was no difference in age or ER/PR status between the two groups. Mig-6 expression prior to treatment did not predict response to progestin therapy (183.5 = responders, 196.6 = non-responders, p=0.47). GPR30 expression prior to progestin treatment was 118.8 for the responders and 68.9 for the non-responders but was not statistically significant (p=0.06). Neither post-treatment Mig-6 (179.1 = responders, 204.0 = non-responders) or GPR30 (103.6 = non-responders, 108.6 = responders) histoscores or change in histoscores pre- and post-treatment predicted response to progestin therapy. Conclusions: BMI but not Mig-6 expression or hormone receptor expression predicted response to progestin therapy in women with endometrial hyperplasia and cancer. GPR30 may have potential as a biomarker of progestin responsiveness but needs to be evaluated in a larger cohort of women. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 362. doi:10.1158/1538-7445.AM2011-362