Prognostic and predictive value of ALDH1, SOX2 and SSEA-4 in bladder cancer

Transurethral resection of bladder tumor (TUR-BT) and radical cystectomy (RC) are standard treatment options for bladder cancer (BC). Neoadjuvant chemotherapy (NAC) prior to RC improves outcome of some patients but currently there are no valid biomarkers to identify patients who benefit from NAC. Presence of cancer stem cells (CSC) has been associated with poor outcome and resistance to chemotherapy in various cancers. Here we studied the expression of stem cell markers ALDH1, SOX2 and SSEA-4 with immunohistochemistry in tissue microarray material consisting of 195 BC patients treated with RC and 74 patients treated with TUR-BT followed by NAC and RC. Post-operative follow-up data of up to 22 years was used. Negative to weak cytoplasmic SOX2 staining was associated with lymphovascular invasion and non-organ confined disease. It was also associated with shortened cancer-specific survival, but the finding was not statistically significant. Contrary to previous reports, none of the other tested biomarkers were associated with cancer-specific mortality or clinicopathological characteristics. Neither were they associated with response to NAC. Despite the promising results of previously published studies, our results suggest that CSC markers ALDH1, SOX2 and SSEA-4 have little if any prognostic or predictive value in BC treated with RC.