Abstract 4996: Expression of the estrogen receptor, progesterone receptor and PTEN in endometrial cancers from women with type II diabetes mellitus
Authors: Roque Dario R. , Dizon Arthur M. , Rambally Brooke , O'Connor Siobhan , Gehrig Paola A. , Denslow Sheri A. , Bae-Jump Victoria L. 
Published: August 2015

Objectives: The anti-diabetic drug, metformin, has been found to decrease proliferation, reduce estrogen receptor (ER) expression and inhibit downstream targets of the mTOR pathway in a pre-operative window study in endometrial cancer patients. Thus, we compared the endometrial cancers between patients with Type II diabetes taking metformin versus those not on metformin, in regards to expression of ER, progesterone receptor (PR) and PTEN.

Methods: Patients with Type II diabetes who underwent surgical staging for endometrial cancer at our institution were identified. These patients were divided into two cohorts based on whether or not they were on metformin. The use of insulin and other anti-diabetic agents was recorded. Using triplicate cores from surgical specimens, a tissue microarray was constructed from formalin-fixed paraffin-embedded hysterectomy specimens. ER, PR and PTEN expression was measured by immunohistochemistry in both the epithelial and stromal components of the tumors. H scores were calculated, averaged among the triplicate cores, and compared between the two groups using Mann-Whitney U test and negative binomial regression analysis.

Results: Triplicate cores were obtained from 162 endometrial cancers from patients with Type II diabetes. Of the 162 patients, 102 (63%) were taking metformin and 60 (37%) were not on metformin. Median BMI for metformin users and non-users was 40 and 37, respectively (p = 0.04). There was no significant difference in tumor stage, grade or histology between the two groups. There was no association between metformin use and PR or PTEN expression. There was a trend towards higher ER expression in the non-metformin users, which was statistically significant for stromal cells (p = 0.04) but not for epithelial cells (p = 0.13). However, when adjusting for age, BMI, race, tumor grade and stage, there was no association between metformin use and ER expression. The median H score for ER did differ between tumors from patients on metformin only (median 26) versus insulin only (median 91), but this was not statistically significant.

Conclusions: Expression of ER, PR and PTEN in endometrial cancers did not differ amongst patients with Type II diabetes regardless of whether their diabetes treatment regimen involved metformin or insulin. Further studies are underway to compare the endometrial cancers of metformin users versus non-users in regards to other insulin and mTOR signaling targets.

Citation Format: Dario R. Roque, Arthur M. Dizon, Brooke Rambally, Siobhan O'Connor, Paola A. Gehrig, Sheri A. Denslow, Victoria L. Bae-Jump. Expression of the estrogen receptor, progesterone receptor and PTEN in endometrial cancers from women with type II diabetes mellitus. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4996. doi:10.1158/1538-7445.AM2015-4996