Kidney Injury Molecule-1 Expression in Pathological T1b Clear Cell Renal Cell Carcinoma: A Putative Biomarker of High Immune-Inflamed Status and Recurrence.

Abstract

Kidney injury molecule-1 (KIM-1) is a potential prognostic marker of advanced-stage clear cell renal cell carcinoma (ccRCC) and is associated with tumor immunogenicity. Little is known about its role in early-stage ccRCC, especially in pathological T1b (pT1b) disease, which shows a higher recurrence rate than pT1a disease. Resected specimens from 112 pT1b ccRCC cases were reviewed and immunohistochemically analyzed for KIM-1 expression. High membranous KIM-1 expression was defined as H score ≥ 140, based on the immunoreactive intensity and area, and cytoplasmic expression in ≥ 10% of cancer cells was considered as high cytoplasmic KIM-1 expression. KIM-1 expression status was compared with clinicopathological variables, including tumor-associated immune cell (TAIC) status. Among the 112 cases, high membranous and cytoplasmic KIM-1 expression was observed in 30 (27%) and 38 (34%) cases, respectively. High membranous KIM-1 expression was significantly associated with a higher nuclear grade, tumor necrosis, hot TAIC status, and shorter recurrence-free survival (RFS) and cancer-specific survival, whereas high cytoplasmic expression was only related to a higher nuclear grade. Multivariate Cox regression analysis revealed that high membranous KIM-1 expression and tumor necrosis were independent predictors of shorter RFS. Our results indicate that membranous KIM-1 expression could be a biomarker for predicting postnephrectomy recurrence in pT1b ccRCC.