Abstract 3674: Protein levels of Piwi-like 1 and -2 protein are prognostic factors for muscle invasive urothelial bladder cancer patients

Abstract

Abstract The Piwi-like proteins are essential for stem-cell maintenance and self-renewal in all multicellular organisms. We analyzed the expression of Piwi-like 1 and Piwi-like 2 by immunohistochemistry (IHC) in 95 muscle invasive bladder cancer (MIBC) samples using tissue microarray. Application of an immunoreactive score (IRS) revealed 37 and 45 patients who were Piwi-like 1 and -2 positive (IRS>2). IHC results were correlated with clinico-pathological and survival data. The expression of both proteins was positively correlated with each other, lymph node metastasis and expression of CK20 and GATA 3. A negative correlation for both proteins was detected for disease-specific survival (DSS), recurrence, Ki67/MIB1 proliferation index, and CK5 expression. Detection of Piwi-like 1 protein positivity was associated with poor DSS (P=0.019; log rank test, Kaplan-Meier analysis), and in multivariate Cox’s analysis (adjusted to tumor stage and tumor grade), it was an independent prognostic factor for DSS (RR=2.16; P=0.011). Piwi-like 2 positivity was associated with DSS (P=0.008) and relapse-free survival (RFS; P=0.040), and in multivariate Cox’s analysis, Piwi-like 2 positivity was an independent prognostic factor for DSS (RR=2.46; P=0.004) and RFS (RR=3.0; P=0.003). Most interestingly, in the basal type patient subgroup (CK5+/CK20−), Piwi-like 2 positivity was associated with poorer DSS, OS and RFS (P<0.001, P<0.001 and P=0.006; log rank test). In multivariate analysis, Piwi-like 2 positivity was an independent prognostic factor for DSS (RR=10.49; P=0.001), OS (RR=5.71; P=0.001) and RFS (RR=6.35; P=0.016). In summary, Piwi-like 1 and -2 positivity are associated with clinico-pathological factors and survival. Therefore, both Piwi-like proteins are suggested as biomarkers for MIBC patients. Citation Format: Markus Eckstein, Rudolf Jung, Katrin Weigelt, Danijel Sikic, Robert Stöhr, Carol Geppert, Abbas Agaimy, Verena Lieb, Arndt Hartmann, Bernd Wullich, Sven Wach, Helge W. Taubert. Protein levels of Piwi-like 1 and -2 protein are prognostic factors for muscle invasive urothelial bladder cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3674.