The clinical prognostic impact of APOBEC3B protein expression in metastatic urothelial carcinoma.

Abstract

544 Background: APOBEC3 enzymes function as a carcinogenic mutagens resulting in substitution of Cytosine to Thymine or Guanine in tCw motif. Mutation signature in urothelial (UC) carcinoma is mediated by APOBEC3 more than smoking which is well known as a risk factor. This study aimed to explore the association of APOBEC3 expression with survival in metastatic UC (mUC). Methods: We examined 94 patients treated with gemcitabine plus platinum chemotherapy for mUC. APOBEC3A and 3B protein expression was measured using immunohistochemistry from archived formalin-fixed paraffin-embedded tissue which was obtained before chemotherapy. Immunohistochemistry results were evaluated by H-score. The cutoff levels of APOBEC3A and 3B expression were calculated with time dependent ROC analysis. Results: APOBEC3B high expression exhibited longer overall survival (OS) and progression-free survival (PFS) than low expression (median OS: 16 months vs 9 months, p=0.032; median PFS: 7 months vs 4 months, p=0.017). APOBEC3A high expression was associated with longer OS (median OS: 13 months vs 9 months, p=0.036; median PFS: 6 months vs 4 months, p=0.405). Disease control (CR/PR/SD) rate (DCR) was higher in APOBEC3B high group than low group (DCR, 79.4% and 57.1%, respectively, p=0.045). Mean H-score of APOBEC3B was higher in disease control group than progressive disease group (mean H-score, 125.3 vs 101.3, p=0.029). APOBEC3A expression was not correlated with chemotherapy response. There was not a significant correlation between APOBEC3A and APOBEC3B (Spearman correlation coefficient=0.111, p=0.319). Conclusions: mUC with APOBEC3B high expression may be associated with better response from gemcitabine plus platinum chemotherapy and longer overall survival. Further functional studies are warranted to clarify the clinical significance of APOBEC3B protein expression in mUC.