Open AccessDownregulation of AGR 2, p21, and cyclin D and alterations in p53 function were associated with tumor progression and chemotherapy resistance in epithelial ovarian carcinoma
Author(s) -
Alves Mariana Rezende,
e Melo Natalia Cruz,
BarrosFilho Mateus Camargo,
Amaral Nayra Soares,
Silva Felipe Ilelis de Barros,
Baiocchi Neto Glauco,
Soares Fernando Augusto,
Brot Andrade Louise,
Rocha Rafael Malagoli
Publication year - 2018
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1530
Subject(s) - immunohistochemistry , ovarian cancer , cancer research , chemotherapy , protein disulfide isomerase , biology , ovarian carcinoma , biomarker , carcinoma , serous carcinoma , serous fluid , pathology , cancer , medicine , biochemistry , enzyme
Anterior gradient 2 protein belongs to a family of chaperone‐like proteins, namely protein disulfide isomerase. Generally, AGR 2 is highly expressed in mucus‐secreting cells and endocrine organs, and in this study, we aimed to evaluate AGR 2 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 CA 125 serum levels were routinely determined. Four‐micrometer‐thick sections were processed by immunohistochemistry using an automated immunostainer, Ventana BenchMark AutoStainer with AGR 2, cyclin D1, p21 WAF 1, and p53. Forty‐nine of 167 cases (29.3%) showed strong to moderate cytoplasmic marking of AGR 2, and 118 (70.7%) had weak to negative expression. The absence of the AGR 2 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 TP 53 gene mutation. This result showed worse DFS alone ( P = .012) and combined with low levels of AGR 2 ( P = .005). The expression profile of AGR 2 and cell cycle proteins here presented was showed as good prognosis marker in epithelial ovarian cancer. This finding suggests AGR 2 and as putative biomarker of disease progression in chemotherapy‐treated high‐grade serous carcinoma patients.