Molecular subtyping of muscle-invasive bladder cancer (MIBC) predicts disease progression and treatment response. However, standard subtyping based on transcriptomic analysis is relatively expensive. This study tried to use immunohistochemistry (IHC) to subtype MIBC based on GATA3, CK20, CK5/6, and CK14 protein expression. The IHC-based subtypes in MIBC subtypes were classified as luminal (GATA3+ CK5/6−, 38.6%), basal (GATA3−CK5/6+, 12.9%), mixed (GATA3+ CK5/6+, 37.9%), and double-negative (GATA3−CK5/6−, 10.6%) in 132 MIBC patients. All individual markers and clinicopathological parameters were analyzed against treatment outcomes after radical cystectomy. The mean patient age was 65.6 years, and the male to female ratio was 6.8:1. Positive IHC expression of GATA3, CK20, CK5/6, and CK14 were 80.3%, 50.8%, 42.4%, and 28.0%, respectively. Only GATA3 and CK5/6 were significantly associated with survival outcome (p values = 0.004 and 0.02). The mixed subtype was significantly better in 5-year OS at 42.8%, whereas the double-negative subtype had the worst prognosis (5-year OS 7.14%). The double-negative subtype had a hazard ratio of 3.29 (95% CI 1.71–6.32). Subtyping using GATA3 and CK5/6 was applicable in MIBCs, and patients with the double-negative subtype were at the highest risk and may require more intensive therapy.
WT1 has been proven to be a prognostic marker and molecular target in various human cancers. In this study, we aimed to investigate the prognostic role of WT1 in colorectal cancers (CRCs). Archival tissue samples from 157 CRC cases who underwent curative surgery in our institute from February 1999 to May 2004 were subjected to WT1 expression studies using an immunohistochemistry technique. Number of positive staining per 500 tumor cells and staining intensities were analyzed against overall survival. Of 157 CRCs, 83 were colonic and 74 were rectal cancers. The mean follow-up period was 116 (range 77-145) months. Five-year and seven-year OS rates were 60.9% and 52.8%, respectively. WT1 immunostaining was positive in 143 cases (91%). The median number of positive cells was 120 (range 0-420). Univariate analysis by Log-rank test showed that AJCC stage, tumor site (rectal cancer), number of positive cells > 120 and high staining intensity (score ++/+++) were significantly associated with poorer survival (p-value < 0.01). Five-year survival rates in cases with positive cells of ⩽ 120 cells and > 120 cells were 72.2% and 49.4%, respectively. Five-year survival in cases with staining intensity of ++ or more was 45.3%, compared with 69% in cases with intensity of less than ++. Multivariate regression analysis demonstrated that the staining intensity, high tumor stage and rectal site were independent factors indicating poorer survival. Our findings indicate that WT1 expression is a marker of poor prognosis in CRCs, independent of AJCC staging.
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