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.