Clinicopathological Significance of Leucine-rich Repeat-containing 15 in Distal Extrahepatic Bile Duct Carcinoma.

Abstract

Leucine-rich repeat-containing 15 (LRRC15) is a membrane protein whose overexpression has been linked to poorer survival outcomes in various malignant neoplasms. However, its role in distal extrahepatic bile duct carcinoma (DBDC) remains unclear. LRRC15 protein expression in tumor cells and stroma was evaluated with 196 surgically resected DBDCs, and compared with clinicopathological variables, including patients' overall survival (OS) and recurrence-free survival (RFS). LRRC15 protein expression was identified in stroma of 21 DBDCs (11%) and tumor cells in 67 cases (34%). On the basis of the combined expression patterns of LRRC15, DBDCs were classified into 4 groups: LRRC15 cancer+/stroma- (25%), cancer-/stroma+ (2%), cancer+/stroma+ (9%), and cancer-/stroma- (64%). The stromal LRRC15+ group exhibited more frequent pancreatic invasion compared with the stromal LRRC15- group ( P =0.004*). The LRRC15 cancer+/stroma+ group showed the most frequent pancreas invasion ( P =0.016*). The patients with stromal LRRC15+ group had significantly worse OS (5-year survival rate, 15.4% vs. 31.6%; P =0.013*) and RFS (19.1% vs. 38.9%; P =0.005*) compared with those in the stromal LRRC15- DBDCs. Stromal LRRC15 expression was significantly associated with poor prognosis and showed a strong trend toward being an independent prognostic factor for both OS ( P =0.051) and RFS ( P =0.061). Patients with DBDCs in the LRRC15 cancer+/stroma+ group had the worst RFS ( P =0.010*) and OS ( P =0.008*) by univariate analysis. LRRC15 overexpression was observed in a subset of DBDCs and was associated with pancreatic invasion and worse OS and RFS. Consequently, LRRC15 expression can be used as an indicator of poor survival in patients with DBDCs, particularly when both cancer cells and stromal expression are present.