High BMI is significantly associated with positive progesterone receptor status and clinico-pathological markers for non-aggressive disease in endometrial cancer

Background: Endometrial cancer incidence is increasing in industrialised countries. High body mass index (BMI, kg m−2) is associated with higher risk for disease. We wanted to investigate if BMI is related to clinico-pathological characteristics, hormone receptor status in primary tumour, and disease outcome in endometrial cancer. Patients and methods: In total, 1129 women primarily treated for endometrial carcinoma at Haukeland University Hospital during 1981–2009 were studied. Body mass index was available for 949 patients and related to comprehensive clinical and histopathological data, hormone receptor status in tumour, treatment, and follow-up. Results: High BMI was significantly associated with low International Federation of Gynaecology and Obstetrics (FIGO) stage, endometrioid histology, low/intermediate grade, and high level of progesterone receptor (PR) mRNA by qPCR (n=150; P=0.02) and protein expression by immunohistochemistry (n=433; P=0.003). In contrast, oestrogen receptor (ERα) status was not associated with BMI. Overweight/obese women had significantly better disease-specific survival (DSS) than normal/underweight women in univariate analysis (P=0.035). In multivariate analysis of DSS adjusting for age, FIGO stage, histological subtype, and grade, BMI showed no independent prognostic impact. Conclusion: High BMI was significantly associated with markers of non-aggressive disease and positive PR status in a large population-based study of endometrial carcinoma. Women with high BMI had significantly better prognosis in univariate analysis of DSS, an effect that disappeared in multivariate analysis adjusting for established prognostic markers. The role of PR in endometrial carcinogenesis needs to be further studied

Low BMI-1 expression is associated with an activated BMI-1-driven signature, vascular invasion, and hormone receptor loss in endometrial carcinoma

We studied the expression of polycomb group (PcG) protein BMI-1 in a large population-based patient series of endometrial carcinomas in relation to clinical and molecular phenotype. Also, 57 fresh frozen endometrial carcinomas were studied for the relationship between BMI-1 protein expression, BMI-1 mRNA level, and activation of an 11-gene signature reported to represent a BMI-1-driven pathway. BMI-1 protein expression was significantly weaker in tumours with vascular invasion (P<0.0001), deep myometrial infiltration (P=0.004), and loss of oestrogen receptor (ER) (P<0.0001) and progesterone receptors (PR) (P=0.03). Low BMI-1 protein expression was highly associated with low BMI-1 mRNA expression (P=0.002), and similarly low BMI-1 mRNA expression correlated significantly with vascular invasion, ER and PR loss, and histologic grade 3. In contrast, activation of the reported 11-gene signature, supposed to represent a BMI-1-driven pathway, correlated with low mRNA expression of BMI-1 (P<0.001), hormone receptor loss, presence of vascular invasion, and poor prognosis. We conclude that BMI-1 protein and mRNA expression are significantly correlated and that BMI-1 expression is inversely associated with activation of the 11-gene signature. Loss of BMI-1 seems to be associated with an aggressive phenotype in endometrial carcinomas