The endoplasmic reticulum stress marker, glucose-regulated protein-78 (GRP78) in visceral adipocytes predicts endometrial cancer progression and patient survival.

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.

Endometriosis in para-aortic lymph nodes during pregnancy: case report and review of literature.

OBJECTIVE: To report a case of endometriosis in para-aortic lymph nodes during pregnancy. DESIGN: Case report. SETTING: Tertiary care center. PATIENT(S): A 25-year-old multipara pregnant woman with a history of chronic pelvic pain and ovarian cystectomies for bilateral endometriomas. INTERVENTION(S): The patient was admitted with a placenta previa and a subchorionic hemorrhage at 24 weeks 5 days' gestation, and subsequently developed uterine contractions. Magnetic resonance imaging revealed a large complex adnexal mass adherent to the uterus and pelvic and para-aortic lymphadenopathy. Tocolysis could not be achieved and the patient underwent cesarean delivery at 26 weeks 3 days. An implant on the uterus and an enlarged para-aortic lymph node were removed surgically at that time. MAIN OUTCOME MEASURE(S): Involvement of lymph node by endometriosis and presence of a recurrent endometrioma. RESULT(S): Endometriosis was confirmed pathologically in para-aortic lymph nodes. Uterine serosal biopsy demonstrated endometriosis, and the large adnexal cyst was grossly consistent with endometrioma. The patient delivered a viable male infant at 26 weeks 3 days. CONCLUSION(S): To our knowledge, this is the first reported case of endometriosis in para-aortic lymph nodes. Its presence supports the hypothesis that endometriosis travels lymphatically, and not simply via locoregional spread. Lymphatic spread also further supports the theory that endometriosis is an aggressive chronic systemic disease.