Variant isoforms of CD44 expression as predictive markers for mortality in surgically treated patients with locally advanced upper tract urothelial carcinoma.

388 Background: The variant isoforms of CD44 (CD44v), which are some of the new cell surface markers for cancer stem cells, have been associated with tumor growth, treatment resistance, and cancer death in several cancers. We investigated the role of CD44v8-10, which is a CD44v, on the clinical outcome of patients with advanced upper tract urothelial cancer (UTUC). Methods: The protein expression of CD44v8-10 was immunohistochemically evaluated using CD44v9 antibody, which detects immunogen of CD44v8-10, and investigated the association with clinical characteristics and outcome in surgical specimens obtained from 110 patients who had been treated with radical nephroureterectomy for ≥pT2 UTUC. The mean percentage of positive cancer cells stained with CD44v9 antibody in each tumor was estimated. Results: The median percentage of CD44v9 positivity was 5.50±7.74%. Patients were subsequently stratified into a CD44v9-positive group (n = 82) and a CD44v9-negative group (n = 28) based on a cut-off level of 5%. During the mean follow-up of 4.8 years, disease recurrence was observed in 49 patients (59.8%) in the CD44v9-positive group and in 8 patients (28.6%) in the CD44v9-negative group. The 5-year recurrence-free survival rates were 47.6% in the CD44v9-positive group and 66.6% in the CD44v9-negative group (p= 0.038). Multivariate analysis showed that tumor grade G3 (p= 0.005, HR = 3.77), the presence of lymphovascular invasion (p= 0.041, HR = 1.84), and CD44v8-10 expression (p= 0.028, HR = 2.33) were independent risk factors for disease recurrence. In this series, 37 patients in the CD44v9-positive group (45.1%) and 5 (17.9%) in the CD44v9-negative group died of the disease. The 5-year cancer-specific survival rates were 57.8% in the CD44v9-positive group and 80.4% in the CD44v9-negative group (p= 0.032). The CD44v9 expression (p= 0.040, HR = 2.67) in addition to tumor grade G3 (p= 0.003, HR = 8.35) were independently associated with cancer death. Conclusions: The expression ofCD44v8-10 may be a new biomarker of malignant potential in locally advanced UTUC and could provide additional prognostic information in patients with UTUC.