A pilot study of the immunohistochemical pattern of neuropilin-2 (NRP2) labeling and correlation with tumor stage in colon cancer.
e14098 Background: Neuropilin 2 (NRP2) is a transmembrane glycoprotein, non-associated with kinase domains, implicated in neovascularization and metastasis of colon cancer. NRP2 has been proposed as a molecular marker for targeted cancer therapy based on its multiple functions in cancer promotion. NRP2 signaling pathway and its expression have been demonstrated in many carcinomas. To the best of our knowledge, no description of the immunohistochemical staining pattern of NRP2 in colon cancer has been published in the English medical literature. The aim of this study is to investigate the NRP2 labelilng pattern in colon cancer and correlate it with tumor stage. Methods: Tumor sections from 35 randomly selected colectomy specimens with colorectal cancer collected during the last three years were retrieved from the University of Toledo Medical Center Department of Pathology archival material. Formalin fixed, paraffin embedded, 4 μm tissue sections containing invasive tumor were immunolabeled with a commercial antibody against NRP2, using a Ventana Benchmark LT automated instrument. Randomized, immunolabeled colon cancer tissue sections were blindly reviewed by two pathologists. Cytoplasmic and nuclear expression of NRP2 by tumor cells was graded as negative (no staining), focal (staining in <50% of cells), and diffuse (staining in ≥ 50% of cells). Adjacent benign colonic mucosa was used as an internal control. Results: No T1 or T2 tumor displayed diffuse nuclear labeling for the NRP2 epitope. In contrast, 13/20 T3 tumors (65%) and 4/4 T4 tumors (100%) displayed diffuse nuclear labeling. The association of diffuse nuclear NRP2 labeling with tumor grade was highly statistically significant (p=0.0055 by Chi-squared test). In contrast to nuclear labeling, cytoplasmic staining was observed in all stages and varied from negative to diffuse, but demonstrated no significant correlation with stage. Conclusions: This pilot study on colon cancer specimens suggests that diffuse nuclear immunolabeling of neuropilin-2 is indicative of a higher tumor stage. This finding suggests a potential use for this marker as a prognostic indicator for colon cancer in small biopsy samples.