Neuropilin-2 expression in cancer

Jubb A M, Sa S M, Ratti N, Strickland L A, Schmidt M, Callahan C A & Koeppen H (2012) Histopathology 61, 340–349 Neuropilin‐2 expression in cancer Aims: Neuropilin‐2 is a coreceptor for vascular endothelial growth factor family members. Blockade of neuropilin‐2 is able to suppress lymphogenous metastasis in preclinical models. The aim of this study was to validate a protocol for the evaluation of neuropilin‐2 protein expression in situ, by comparison with in‐situ hybridization, western blotting, and mRNA expression levels. Methods and results: Immunohistochemistry was performed on normal human tissues, and whole sections for 79 primary non‐small‐cell lung carcinomas, 65 primary breast carcinomas, 79 primary colorectal cancers, and 52 metastases. Neuropilin‐2 expression was observed in lymphatic and blood vessels from all normal and malignant tissues examined. In addition, 32% of primary non‐small‐cell lung carcinomas, 15% of primary breast carcinomas and 22% of primary colorectal cancers showed tumour cell expression. Fifty‐five primary and nine secondary malignant melanomas were also examined for neuropilin‐2 expression by in‐situ hybridization. All showed vascular expression, and 85% of primary malignant melanomas showed tumour cell expression. Conclusions: In the majority of lung, breast and colorectal cancers, the effects of anti‐neuropilin‐2 are likely to be restricted to the vasculature. These results will assist in pharmacokinetic evaluations, tolerability assessments and the choice of setting to evaluate the activity of anti‐neuropilin‐2 therapies.