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Abstract: Anterior gradient 2 protein belongs to a family of chaperone‐like proteins, namely protein disulfide isomerase. Generally, AGR2 is highly expressed in mucus‐secreting cells and endocrine organs, and in this study, we aimed to evaluate AGR2 and cell cycle molecules in epithelial ovarian cancer and its implications on prognosis. One hundred seventy‐five patient's samples that were diagnosed with primary epithelial ovarian carcinoma were selected. All the patients were treated with platinum‐taxane standard chemotherapy after surgery and CA125 serum levels were routinely determined. Four‐micrometer‐thick sections were processed by immunohistochemistry using an automated immunostainer, Ventana BenchMark AutoStainer with AGR2, cyclin D1, p21WAF1, and p53. Forty‐nine of 167 cases (29.3%) showed strong to moderate cytoplasmic marking of AGR2, and 118 (70.7%) had weak to negative expression. The absence of the AGR2 protein was observed in high‐grade serous carcinoma (P < .001) and significantly associated with disease‐free survival (DFS; P = .034). The expression of G1‐S phase‐regulatory proteins showed loss of p21 in high‐grade serous carcinoma (P < .001) and was related with poor DFS (P = .003). Strong and diffuse immunoexpression of p53 plus complete absence of p53 staining was interpreted as likely indicating a TP53 gene mutation. This result showed worse DFS alone (P = .012) and combined with low levels of AGR2 (P = .005). The expression profile of AGR2 and cell cycle proteins here presented was showed as good prognosis marker in epithelial ovarian cancer. This finding suggests AGR2 and as putative biomarker of disease progression in chemotherapy‐treated high‐grade serous carcinoma patients. [ABSTRACT FROM AUTHOR]

Aims: High grade serous carcinoma (HGSC) is an aggressive tumour, and most patients relapse after treatment, acquiring resistance to platinum-based chemotherapy. One of the resistance mechanisms proposed is apoptosis evasion triggered by drug-related cytotoxic effect in the cell. In this context, this study aims to evaluate the protein expression of GRIM-19, NF-κB and IKK2, their association with chemotherapy response and to determine their prognostic values in HGSC., Methods: GRIM-19, NF-κB and IKK2 expression was evaluated by immunohistochemistry (IHC) in 71 patients with HGSC selected between 2003 and 2013, whose underwent primary debulking surgery with complete cytoreduction. Protein expression was analyzed in relation to platinum response groups, tumour progression, clinicopathological data and survival., Results: Positive IKK2 expression was related to resistance (p = 0.011), shorter disease-free survival (p = 0.001) and overall survival (p = 0.026) and was also a risk factor for relapse (p = 0.002) and death (p = 0.032). The association between IKK2 and NF-κB positivity predicted a subgroup with shorter overall survival (p = 0.004), disease-free survival (p = 0.003) and resistance to platinum-based chemotherapy (p = 0.036). NF-κB positivity was associated with worse overall survival (p = 0.005) and disease-free survival (p = 0.027) and was a positive predictor for relapse (p = 0.032) and death (p = 0.008). Higher expression of GRIM-19 was associated with higher disease-free survival (p = 0.039) and was a negative predictor for relapse (p = 0.046)., Conclusions: GRIM-19 is a potential predictor of prognosis and disease recurrence in HGSC. IKK2 and NF-κB are related to poor prognosis and are potential predictors of response to platinum-based chemotherapy in HGSC. IHC analyses of GRIM19, IKK2 and NF-κB may be important in the attempt to provide prognostic values for relapse and response to treatment in patients with HGSC., (Copyright © 2017 Elsevier GmbH. All rights reserved.)