Investigation of GREMLIN 1, COL15A1 immunoreactivity and the relationship between microvessel density and GREMLIN 1 in papillary renal cell carcinoma and chromophobe renal cell carcinoma

Abstract

Objective: The current study aimed to investigate expressions of Gremlin 1 (GREM1) (a bone morphogenetic protein antagonist and a proangiogenic factor) and COL15A1 (Collagen type XV alpha-1, encodes the proteoglycans located in various human tissues and particularly in the basement membrane) immunohistochemically in papillary renal cell carcinoma (PRCC) and chromophobe renal cell carcinoma (CRCC) in order to assess the relationship between these markers and said tumors and also explore associations of GREM1 with angiogenesis, tumor necrosis and tumor diameter by looking at the microvascular density (MVD) through the expression of COL15A1 in vascular endothelium. Material and Method: GREM1 and COL15A1 expressions were investigated in 20 PRCC and 39 CRCC patients. Cytoplasmic staining with GREM1 and COL15A1 was examined. Microvascular structures stained with COL15A1 were examined in order to evaluate angiogenic profile. Results: In CRCC, GREM1 staining was statistically significant in tumor tissues compared to intact tissues (p=0.006). The relationship between MVD and GREM1 staining was statistically significant in PRCC (p=0.007). Cytoplasmic staining with COL15A1 observed in PRCC was statistically significant (p=0.005). Conclusion: Positive GREM1 staining observed in both tumor groups and much higher expression of this marker particularly in the tubular epithelium of the neighboring normal tissue supports our argument that this gene might be a tumor suppressor gene.