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MP63-08 CD44 VARIANT 9 EXPRESSION IS A NOVEL INDICATOR FOR IDENTIFYING POOR SURVIVAL IN PATIENTS WITH INVASIVE UROTHELIAL CARCINOMA

INTRODUCTION AND OBJECTIVES: CD44 is reported as major cell surface marker for cancer stem cells (CSCs) in various types of cancers. Previous studies revealed that the variant isoform of 9 (CD44v9) have been associated with their features of CSCs, which induce tumor recurrence and metastasis. However, little is known with respect to whether expression of CD44v9 could be associated with clinical outcome in ≥pT2 invasive urothelial carcinoma (UC). METHODS: We identified 182 patients who were treated with radical nephroureterectomy for invasive upper tract urothelial carcinoma (UTUC, n=119) or radical cystectomy for invasive bladder cancer (BC, n=63) between 1999 and 2007 at our institution and investigated the association between the expression of CD44v9 evaluated by immunohistochemical staining and their prognosis. To evaluate CD44v9 staining, cancer cells with high staining in the cell membrane were counted in at least 10 representative fields, and the mean percentage of high cancer cells was estimated. RESULTS: The median value of the CD44v9 density was 5.5%. Patients were subsequently allocated into a CD44v9-high group (n=123) and a CD44v9-low group (n=59) based on a cut-off level of 5%. The 5-year cancer-specific survival (CSS) rate in the CD44v9-high group was 59.3%, which was significantly lower than that in the CD44v9-low group (86.4%, p<0.001). Multivariate analysis revealed that CD44v9 positivity (hazard ratio: HR, 5.18, p=0.001) was an independent risk factor for cancer-specific death in addition to high grade tumor (HR, 3.66, p=0.031) and pN positive (HR, 2.63, p=0.006). Furthermore, CD44v9 positivity (HR, 3.39, p=0.001) was independently associated with disease recurrence in addition to pN positive (HR, 3.39, p<0.001). In a subgroup of 63 invasive BC patients, the 5-year CSS rate in the CD44v9-high group was 52.7% (n=36), which was significantly lower than that in the CD44v9-low group (n=27, 95.2%, p=0.017) and CD44v9 positivity (HR, 9.19, p=0.034) was the only independent risk factor for cancer-specific death. In a subgroup of 119 invasive UTUC patients, the 5-year CSS rate in the CD44v9-high group was 55.2% (N=87), which was significantly lower than that in the CD44v9-low group (N=32, 79.6%, p=0.017) and CD44v9 positivity (HR, 3.22, p=0.009) was the only independent risk factor for cancer-specific death. CONCLUSIONS: CD44v9 could be a strong prognostic indicator in invasive BC as well as UTUC. Information of CD44v9 positivity might be useful for the appropriate selection of adjuvant systemic therapy in patients with pT2-4N0M0 UC who undergo surgical treatment. Source of Funding: none