Immunohistochemical Markers for Risk Stratification of Patients with Muscle-Invasive Bladder Cancer - Expert Commentary

The relationship between the expression of GATA3, cytokeratin (CK) 20, CK 5/6, and p53 and survival in patients with muscle-invasive bladder cancer (MIBC) is not well characterized.

A recent study published by Wang et al. in PLOS ONE investigated the prognostic value and the clinical use of immunohistochemical (IHC) staining for GATA3, cytokeratin (CK) 20, CK 5/6, and p53 in the molecular classification and risk stratification in MIBC. The investigators included 91 patients who underwent radical cystectomy for MIBC.

The researchers analyzed the association between the Ki-67 proliferation index and these IHC markers. Tumors with negative CK20 (p= 0.002) and diffuse CK5/6 (p = 0.001) were associated with a higher Ki-67 index. On the other hand, a low Ki-67 index was associated with diffuse GATA3 (p = 0.006). Compared to partial p53 staining, tumor cells with no p53 staining was associated with a significantly high Ki-67 index (p = 0.004). Tumor cells with diffuse strong nuclear p53 staining and strong cytoplasmic staining were associated with a high Ki-67 index in comparison to other patterns (p < 0.001). CK20 and CK5/6 expression showed a reciprocal pattern. 13 (14.29%) cases presented with coexpression of GATA3 and CK5/6 in a diffuse staining pattern. Unlike CK20, CK5/6, p53, and Ki-67, GATA3 correlated with clinical outcome. In the chemotherapy-naïve group (78 patients), higher GATA3 staining was associated with higher recurrence-free survival in both univariate (p = 0.008) and multivariate (p = 0.002) analysis.

The authors conclude that GATA3 expression could play a role in the risk stratification of patients with MIBC. While IHC has been the most commonly used method for the development of potential prognostic and predictive biomarkers, this method has significant limitations. In the future, we anticipate that newer technologies for quantifying messenger RNA and protein will start to replace IHC in biomarker development.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York


1. Wang, Chung-Chieh, Yu-Chieh Tsai, and Yung-Ming Jeng. "Biological significance of GATA3, cytokeratin 20, cytokeratin 5/6 and p53 expression in muscle-invasive bladder cancer." PloS one 14, no. 8 (2019).

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