Abstract 4130: Frequency and prognostic value of PTEN loss in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy

Abstract

Abstract Objective To analyze PTEN expression status and its association with disease recurrence and survival outcomes in a large, multi-institutional upper tract urothelial carcinoma (UTUC) cohort. Design, Setting, Participants Retrospective analysis of 611 patients with UTUC treated with radical nephroureterectomy (RNU) between 1991 and 2008 at seven institutions. Median follow-up was 23 months (interquartile range, 6-40). Tissue microarrays andimmunohistochemical PTEN staining (monoclonal antibody) was performed. Interventions RNU for UTUC with or without adjuvant chemotherapy. Results PTEN staining was absent in 45 (7.4%) of the cases. Patients with PTEN loss had significantly advanced pathological tumor stage and grade (p<0.001), higher rate of lymph node metastasis (p<0.01), and lymphovascular invasion (p<0.001) compared to patients with PTEN expression. PTEN loss was associated with disease recurrence, cancer-specific, and overall mortality in univariable Cox regression analyses. However, in multivariable Cox regression analyses that adjusted for the effect of standard clinicopathologic features, PTEN loss was notassociated any more with disease recurrence or cancer-specific mortality, but with overall mortality. Conclusions In patients undergoing RNU for UTUC, loss of PTEN protein expression is relatively uncommon, but when present associated with features of biologically aggressive disease such as higher grade and stage as well as lymph node metastasis. Loss of PTEN expression was associated with disease recurrence and cancer-specific survival after RNU for UTUC in univariable, but not in multivariable, analysis. PTEN loss seems to promote worse outcomes in the relatively small group of patients. Table 3. Multivariable Cox regression analyses predicting disease recurrence, cancer-specific mortality and overall mortality in 611 patients treated with radical nephroureterectomy for upper urinary tract urothelial cancer. Table 3.Multivariable Cox regression analyses predicting disease recurrence, cancer-specific mortality and overall mortality in 611 patients treated with radical nephroureterectomy for upper urinary tract urothelial cancer.CharacteristicsDisease recurrenceCancer-specific mortalityOverall mortalityHR95% CIp valueHR95% CIp valueHR95% CIp valueAge (continuous)1.010.99-1.030.091.031.01-1.040.0081.041.03-1.06<0.001Pathological tumor stagepT0, pTis, pTa,-Referent<0.001-Referent<0.001-Referent<0.001pT14.71.08-20.460.046.390.83-49.250.080.960.51-1.800.89pT28.421.93-36.690.00514.271.88-108.440.011.290.68-2.450.44pT316.323.85-69.23<0.00122.913.08-170.760.0022.041.10-3.790.02pT473.7216.09-337.7<0.00194.0611.82-748.82<0.0017.043.27-15.17<0.001High grade vs. low grade tumor1.120.65-1.930.691.350.74-2.470.331.591.02-2.500.04Nodal statuspN0-Referent0.005-Referent0.007-Referent0.04pNx0.760.48-1.220.250.830.49-1.420.51.030.67-1.590.89pN+1.660.92-2.990.091.90.99-3.650.051.821.03-3.230.04Tumor multifocality1.501.02-2.200.041.621.08-2.440.021.691.22-2.330.002Presence of LVI1.200.82-1.750.341.450.98-2.170.071.340.96-1.890.09Presence of concomitant Cis1.280.84-1.950.260.930.58-1.490.770.990.68-1.460.98Sessile vs. papillary architecture1.541.03-2.320.041.601.02-2.520.041.681.17-2.430.005Presence of Necrosis0.520.32-0.840.0080.480.27-0.840.010.780.51-1.200.26Administration of adjuvant chemotherapy1.711.11-2.640.021.110.68-1.820.680.910.58-1.430.69Loss of PTEN vs. PTEN expression1.280.80-2.050.311.320.78-2.230.311.691.09-2.610.02 Citation Format: Daniel Lee, Malte Rieken, Sharokh Shariat, Evanguelos Xylinas, Christopher Wood, Jose Karam, Alon Weiner, Charles Guo, Yair Lotan, angelo Marzo, Brian Robinson, Vitaly Margulis. Frequency and prognostic value of PTEN loss in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4130. doi:10.1158/1538-7445.AM2014-4130