Downregulation of AGR2, p21, and cyclin D and alterations in p53 function were associated with tumor progression and chemotherapy resistance in epithelial ovarian carcinoma.

Autor: Alves MR; International Research Center, AC Camargo Cancer Center, São Paulo, Brazil., E Melo NC; Molecular Gynecology Laboratory, Gynecologic Department, Federal University of São Paulo, São Paulo, Brazil., Barros-Filho MC; International Research Center, AC Camargo Cancer Center, São Paulo, Brazil., do Amaral NS; International Research Center, AC Camargo Cancer Center, São Paulo, Brazil., Silva FIB; International Research Center, AC Camargo Cancer Center, São Paulo, Brazil., Baiocchi Neto G; Department of Gynecology Oncology, AC Camargo Cancer Center, São Paulo, Brazil., Soares FA; Department of Anatomic Pathology, A.C. Camargo Cancer Center, São Paulo, Brazil., de Brot Andrade L; Department of Anatomic Pathology, A.C. Camargo Cancer Center, São Paulo, Brazil., Rocha RM; Molecular Gynecology Laboratory, Gynecologic Department, Federal University of São Paulo, São Paulo, Brazil.
Jazyk: angličtina
Zdroj: Cancer medicine [Cancer Med] 2018 Jul; Vol. 7 (7), pp. 3188-3199. Date of Electronic Publication: 2018 May 29.
DOI: 10.1002/cam4.1530
Abstrakt: 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.
(© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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