Adiponectin, Leptin, and Insulin-Pathway Receptors as Endometrial Cancer Subtyping Markers.
Evan L Busch, Marta Crous-Bou, Jennifer Prescott, Michael J Downing, Bernard A Rosner, George L Mutter, Immaculata De Vivo
Author Information
Evan L Busch: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, 3rd Floor, Boston, MA, 02115, USA.
Marta Crous-Bou: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, 3rd Floor, Boston, MA, 02115, USA.
Jennifer Prescott: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, 3rd Floor, Boston, MA, 02115, USA.
Michael J Downing: Division of Women's and Perinatal Pathology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
Bernard A Rosner: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, 3rd Floor, Boston, MA, 02115, USA.
George L Mutter: Division of Women's and Perinatal Pathology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
Immaculata De Vivo: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, 3rd Floor, Boston, MA, 02115, USA. nhidv@channing.harvard.edu.
Developing a system of molecular subtyping for endometrial tumors might improve insight into disease etiology and clinical prediction of patient outcomes. High body mass index (BMI) has been implicated in development of endometrial cancer through hormonal pathways and might influence tumor expression of biomarkers involved in BMI-sensitive pathways. We evaluated whether endometrial tumor expression of 7 markers from BMI-sensitive pathways of insulin resistance could effectively characterize molecular subtypes: adiponectin receptor 1, adiponectin receptor 2, leptin receptor, insulin receptor (beta subunit), insulin receptor substrate 1, insulin-like growth factor 1 receptor, and insulin-like growth factor 2 receptor. Using endometrial carcinoma tissue specimens from a case-only prospective sample of 360 women from the Nurses' Health Study, we scored categorical immunohistochemical measurements of protein expression for each marker. Logistic regression was used to estimate associations between endometrial cancer risk factors, especially BMI, and tumor marker expression. Proportional hazard modeling was performed to estimate associations between marker expression and time to all-cause mortality as well as time to endometrial cancer-specific mortality. No association was observed between BMI and tumor expression of any marker. No marker was associated with time to either all-cause mortality or endometrial cancer-specific mortality in models with or without standard clinical predictors of patient mortality (tumor stage, grade, and histologic type). It did not appear that any of the markers evaluated here could be used effectively to define molecular subtypes of endometrial cancer.
References
Cancer Epidemiol Biomarkers Prev. 2017 May;26(5):727-735
[PMID: 28052940]
