Endometrial expression of hormonal and insulin/IGF receptors in relation to cancer risk factors

Abstract

Objectives: The aim was to investigate, in a prospective cohort of postmenopausal women, endometrial tissue expression of hormonal and insulin/insulin like growth factor (IGF) receptors in relation to cancer risk factors. Methods: This institutional review board–approved prospective study enrolled 50 postmenopausal women undergoing hysterectomy. Clinical data were obtained using a study questionnaire. Immunohistochemical (IHC) staining was done on formalin-fixed paraffin-embedded endometrial tissue sections using primary antibodies specific for estrogen receptor alpha (ERα), progesterone receptor (PR), type 1 IGF receptor (IGF1R), insulin receptor (IR), and phosphorylated IR/IGF1R (p-IR/IGF1R). The study pathologist evaluated staining intensity and percentage of positive cells; receptor expression was categorized as positive or negative, as previously described. Statistical significance of receptor expression differences according to risk factor categories was evaluated with the Fisher exact test. P < .05 was considered significant; analyses were performed using R version 3.1.1. Results: Patients completing the study questionnaire and from whom sufficient endometrial tissue was obtained were eligible for analysis (n = 29). The mean age was 60.9 years. The mean body mass index was 29.3 kg/m2. The primary indications for hysterectomy were uterine prolapse or leiomyomata. Twenty-eight percent were diabetic. Diabetics were more likely to have positive endometrial glandular expression of p-IGF1R/IR (P = .02). Forty-eight percent reported NSAID use. Women reporting NSAID use were more likely to have positive PR expression in the endometrial stromal tissue (P = .01). Conclusions: This is the first study to evaluate the relationship of hormonal and insulin/IGF receptor expression in normal postmenopausal endometrium, in relation to cancer risk factors. Our finding of increased insulin/IGF receptor activation in diabetics suggests that detectable signaling alterations in the endometrium may precede neoplastic transformation in these at-risk women. NSAID usage has been linked to decreased endometrial cancer risk in epidemiologic studies. The increased PR expression observed in the endometrial stromal tissue of NSAID users may be associated with a novel mechanism of cancer protection. In summary, clinical cancer risk factors are associated with altered receptor expression in nonmalignant endometrium, and should be further investigated as biomarkers in cancer risk assessment and prevention studies.