Abstract 784: Plasmacytoid urothelial carcinoma: Molecular and histopathological characterization of a rare variant of bladder cancer

Abstract

Abstract AIM: The plasmaycytoid urothelial carcinoma (PUC) is a rare variant of urothelial carcinoma. To date only few cases have been reported and molecular data are not published yet. Therefore, we analysed clinical, histopathological and molecular features in a series of 32 PUC. METHODS: Expression of CK7, CK20, PAN-CK, p53, Ki67, CD138, E-cadherin and beta-catenin was analysed immunohistochemically on a tissue microarray. UroVysion FISH was performed to asses ploidy status. After microdissection and DNA isolation, FGFR3 and PIK3CA mutation status were determined using SNaPshot analysis. P53 mutation analysis was performed by direct sequencing of exons 5-9. Clinical data available from 16 PUC were compared to 269 patients with conventional locally advanced urothelial bladder cancer within a randomized multicenter trial (AUO-AB 05/95). RESULTS: PUC were usually diagnosed in advanced pathologic stage (64% pT3, 23% pT4) with 60% metastatic disease. Overall survival of PUC treated with cystectomy and adjuvant chemotherapy was lower than of patients with conventional locally advanced bladder cancer (23.3 vs. 49.9 months, p=0.051). 87% of PUCs showed loss or strongly reduced expression of E-cadherin. Beta-catenin was completely absent in 22.5% and associated with loss of E-cadherin (p=0.033). 16.7% of PUC showed a nuclear staining for beta-catenin, which was more frequent in E-cadherin negative PUC. CK20 expression was abnormal in all cases. 22.6% of PUCs were negative for CK7. 97% of PUC displayed a positive PAN-CK staining. 78% coexpressed CD138. Nuclear accumulation of P53 was found in 68.4% of E-cadherin negative PUC, but only in 27.2% of E-cadherin positive ones. p53 mutations were found in 9/31 cases. 69% of PUC showed increased Ki67 labelling index (>15%). FISH displayed PUC as highly aneuploid tumors. Relative deletion of 9p21 was found in 70%. No mutations were found in FGFR3 and PIK3CA. CCONCLUSIONS: PUC showed molecular and histopathologic features of aggressive bladder cancer. Prognosis in locally advanced PUC treated with adjuvant chemotherapy seems to be unfavourable in comparison to conventional bladder cancer. Loss of E-Cadherin is present in the majority of PUC and is associated with a higher degree of p53 and beta-catenin accumulation, which is in line with the high metastatic potential of PUC. CD 138 is not suitable for differential diagnosis to plasmocytoma. PAN CK is an important diagnostic tool for clarification of the epithelial origin of PUC as there are cases negative for CK7 and CK20. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 784.