PIK3CA Mutational Analysis in Formalin-Fixed, Paraffin-Embedded Archival Tissues of Urothelial Carcinoma of Urinary Bladder

Objective: Urothelial carcinoma of the urinary bladder is the fourth most common cancer in males in the United States. In addition to mutations in FGFR3, TP53, AKT1, TSC1, and PTEN genes, mutations in PIK3CA have been also described in urothelial carcinomas, preferentially in low-grade tumors. Mutations in PIK3CA also has been shown to have implications for prognosis, surveillance and therapeutic response. Thus, determining the PIK3CA status in urothelial carcinomas could potentially improved the clinical management of patients with bladder cancer. Herein, we evaluated the presence of PIK3CA mutations in exons 1, 9, and 20 in 21 urothelial carcinomas of the urinary bladder. Methods: Patients were treated by radical cystectomy without neoadjuvant chemotherapy. Representative tissue blocks (1 for each case) were selected. We used a pinpoint DNA extraction technique from formalin-fixed, paraffin-embedded and mutational analysis using the polymerase chain reaction (PCR) assay coupled with sequencing of targeted exons. Patients included 15 men and 6 women, with a median age of 68 years (range, 42 to 76 years), with 3 noninvasive and 18 invasive urothelial carcinomas. Noninvasive carcinomas included 1 case each of low-grade papillary urothelial carcinoma, high-grade papillary urothelial carcinoma, and urothelial carcinoma in situ (CIS). Invasive tumors included 3 pT1, 5 pT2, 6 pT3, and 4 pT4 urothelial carcinomas. Results: We did not find mutations in the analyzed exons of the PIK3CA gene, in any of the 21 urothelial carcinomas. The preponderance of invasive high-grade and high-stage tumors could explain the absence of identifiable mutations in our cohort. Conclusions: PIK3CA mutations as prognosticators of outcome or predictors of therapeutic response await further evaluation.