Biological significance of GATA3, cytokeratin 20, cytokeratin 5/6 and p53 expression in muscle-invasive bladder cancer
Journal
PLoS ONE
Journal Volume
14
Journal Issue
8
Pages
e0221785
Date Issued
2019
Author(s)
Abstract
Genetic profiling studies on muscle-invasive bladder cancers (MIBCs) have discovered molecular subtypes with different biological characteristics. Immunohistochemical (IHC) markers such as GATA3, cytokeratin (CK) 20, CK5/6, and p53 are associated with these subtypes. In this study, we investigated the biological and prognostic significance of these IHC markers in MIBCs from 91 patients who underwent radical cystectomy. High Ki-67 indices were associated with negative CK20 (p = 0.002) and diffuse CK5/6 (p = 0.001) staining. By contrast, tumors with diffuse GATA3 expression had low Ki-67 index (p = 0.006). Regarding p53, three staining patterns were associated with a high Ki-67 index: (1) complete absence, (2) diffusely strong nuclear reactivity, and (3) diffusely strong cytoplasmic staining (p < 0.001 compared with other patterns). CK5/6 and CK20 expression was typically present in a reciprocal fashion; however, diffuse GATA3 and CK5/6 coexpression was observed in 13 (14.29%) cases. Among 78 chemotherapy-na?ve patients, low GATA3 staining was associated with worse recurrence-free survival in both univariate (p = 0.008) and multivariate analyses (p = 0.002). CK20, CK5/6, or p53 expression was not associated with clinical outcome. Based on our results, IHC staining for GATA3 may help risk stratification in patients with MIBC receiving radical cystectomy. In addition, the differences in Ki-67 indices suggested that aberrant p53 expression was better defined by the three aforementioned patterns, rather than percentage of nuclear staining alone. ? 2019 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
SDGs
Other Subjects
antineoplastic agent; cytokeratin 20; cytokeratin 5; cytokeratin 6; Ki 67 antigen; protein p53; transcription factor GATA 3; GATA3 protein, human; keratin; protein p53; transcription factor GATA 3; tumor marker; adult; aged; Article; cancer chemotherapy; cancer inhibition; cancer prognosis; cancer staging; controlled study; cystectomy; disease specific survival; female; human; immunohistochemistry; major clinical study; male; muscle invasive bladder cancer; overall survival; protein expression; protein function; recurrence free survival; staining; bladder tumor; genetics; metabolism; middle aged; mortality; pathology; prognosis; proportional hazards model; tumor invasion; very elderly; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Female; GATA3 Transcription Factor; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Prognosis; Proportional Hazards Models; Tumor Suppressor Protein p53; Urinary Bladder Neoplasms
Publisher
Public Library of Science
Type
journal article