OBJECTIVE: Currently, accurately identifying endometrial cancer patients at high risk for recurrence remains poor. To ascertain if changes in the endoplasmic reticulum (ER) stress marker, glucose-regulated-protein-78 (GRP78) can serve as a prognosticator in endometrial cancer, we examined GRP78 expression in patient samples to determine its association with clinical outcome. METHODS: A retrospective cohort study was conducted in endometrial cancer patients. Archived specimens of visceral adipocytes and paired endometrial tumors were analyzed by immunohistochemistry for GRP78 and another ER stress marker, C/EBP homologous protein (CHOP). Expression of these markers was correlated with clinico-pathological information and outcomes. RESULTS: GRP78 expression in visceral adipocytes was detected in 95% of the 179 endometrial cancer patients with analyzable visceral adipocytes. Within individual samples, 24% of adipocytes (range, 0-90%, interquartile range 18%-38%) exhibited GRP78 expression. High visceral adipocyte GRP78 expression positively correlated with advanced-stage disease (p=0.007) and deep myometrial invasion (p=0.004). High visceral adipocyte GRP78 expression was significantly associated with decreased disease-free survival (DFS) in multivariate analyses (hazard ratio 2.88, 95% CI 1.37-6.04, p=0.005). CHOP expression paralleled the GRP78 expression in adipocytes (r=0.55, p<0.001) and in the tumor (p=0.018). CONCLUSIONS: Our study demonstrates that the ER stress markers, GRP78 and CHOP, are elevated in endometrial cancer patients. Furthermore, GRP78 expression levels in visceral adipocytes from these patients were significantly correlated to disease stage and patient survival. Our results demonstrate, for the first time, that the GRP78 levels in endometrial cancer patients may be a prognosticator and aid with clinical risk stratification and focused surveillance.
OBJECTIVE: Currently, accurately identifying endometrial cancerpatients at high risk for recurrence remains poor. To ascertain if changes in the endoplasmic reticulum (ER) stress marker, glucose-regulated-protein-78 (GRP78) can serve as a prognosticator in endometrial cancer, we examined GRP78 expression in patient samples to determine its association with clinical outcome. METHODS: A retrospective cohort study was conducted in endometrial cancerpatients. Archived specimens of visceral adipocytes and paired endometrial tumors were analyzed by immunohistochemistry for GRP78 and another ER stress marker, C/EBP homologous protein (CHOP). Expression of these markers was correlated with clinico-pathological information and outcomes. RESULTS:GRP78 expression in visceral adipocytes was detected in 95% of the 179 endometrial cancerpatients with analyzable visceral adipocytes. Within individual samples, 24% of adipocytes (range, 0-90%, interquartile range 18%-38%) exhibited GRP78 expression. High visceral adipocyte GRP78 expression positively correlated with advanced-stage disease (p=0.007) and deep myometrial invasion (p=0.004). High visceral adipocyte GRP78 expression was significantly associated with decreased disease-free survival (DFS) in multivariate analyses (hazard ratio 2.88, 95% CI 1.37-6.04, p=0.005). CHOP expression paralleled the GRP78 expression in adipocytes (r=0.55, p<0.001) and in the tumor (p=0.018). CONCLUSIONS: Our study demonstrates that the ER stress markers, GRP78 and CHOP, are elevated in endometrial cancerpatients. Furthermore, GRP78 expression levels in visceral adipocytes from these patients were significantly correlated to disease stage and patient survival. Our results demonstrate, for the first time, that the GRP78 levels in endometrial cancerpatients may be a prognosticator and aid with clinical risk stratification and focused surveillance.
Authors: Koji Matsuo; Marc R Gualtieri; Sigita S Cahoon; Carrie E Jung; Richard J Paulson; Donna Shoupe; Laila I Muderspach; Akihiko Wakatsuki; Jason D Wright; Lynda D Roman Journal: Menopause Date: 2016-02 Impact factor: 2.953
Authors: Kunyu Shen; David W Johnson; David A Vesey; Michael A McGuckin; Glenda C Gobe Journal: Cell Stress Chaperones Date: 2017-09-27 Impact factor: 3.667
Authors: Mayurbhai R Patel; Stephen D Kozuch; Christopher N Cultrara; Reeta Yadav; Suiying Huang; Uri Samuni; John Koren; Gabriela Chiosis; David Sabatino Journal: Nano Lett Date: 2016-10-03 Impact factor: 11.189
Authors: Y G Lin; J Shen; E Yoo; R Liu; H-Y Yen; A Mehta; A Rajaei; W Yang; P Mhawech-Fauceglia; F J DeMayo; J Lydon; P Gill; A S Lee Journal: Oncogene Date: 2015-02-16 Impact factor: 9.867