High Levels of Phosphatase and Tensin Homolog Expression Are Associated With Tumor Progression, Tumor Recurrence, and Systemic Metastases in pT1 Urothelial Carcinoma of the Bladder: A Tissue Microarray Study of 156 Patients Treated by Transurethral Resection

OBJECTIVE To evaluate immunohistochemical expression of phosphatase and tensin homolog (PTEN) and mammalian target of rapamycin (mTOR) pathway members in pT1 urothelial carcinomas treated by transurethral resection and to determine if immunohistochemistry can be used to predict prognosis. METHODS Formalin-fixed, paraffin-embedded tissue samples from 156 patients with pT1 urothelial carcinoma treated by transurethral resection were used to build 5 tissue microarrays. Tissue microarray sections were stained for PTEN, phosphorylated (phos)-AKT, phos-mTOR, phos-S6, eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1), and phos-4EBP1. Patients were monitored after initial treatment (mean, 22.5; median, 16; range, 3-108 months) to detect tumor recurrence, tumor progression, or systemic metastases. RESULTS During follow-up, 101 patients (65%) showed tumor recurrence, 57 showed tumor progression (37%), and 18 showed systemic metastases (12%). Patients with >= 2 lesions at the initial workup had higher proportions and higher hazard ratios of tumor recurrence, tumor progression, and systemic metastases. Complete loss of PTEN expression was observed in 6 patients (4%), and >80% of the mTOR pathway members showed at least focal positivity. Proportions of tumors with higher levels of PTEN immunohistochemical expression were higher in patients with tumor recurrence (P = .001), tumor progression (P = .05), and systemic metastases (P = .001). Proportions of tumors with lower phos-S6 and low phos-4EBP1 levels were higher in patients with tumor recurrence (P <= .05). Proportions were similar for the remaining biomarkers. CONCLUSION Higher levels of PTEN immunohistochemical expression were associated with higher rates of tumor recurrence, tumor progression, and systemic metastases in patients with pT1 urothelial carcinomas treated by transurethral resection. UROLOGY 81: 116-122, 2013. (c) 2013 Elsevier Inc.