Neuropilin-1 expression in squamous cell carcinoma of the oesophagus

Abstract

OBJECTIVES: The development of new therapeutic targets is needed to change the current low survival rates of cancer of the oesophagus. In some clinical trials, angiogenic inhibitors, including those targeting the vascular endothelial growth factor (VEGF) and its receptors, have proven efficacious. In concert with this, neuropilin-1 (NRP1), a coreceptor for VEGF, is expressed by many tumours and may be related to their progression. This study aimed to assess the expression and prognostic value of fNRP1 in primary squamous cell carcinoma (SCC) of the oesophagus. METHODS: The expression of NRP1 receptors was assessed in 60 samples of resected oesophageal SCC and adjacent normal mucosa by western blotting, immunostaining and real-time quantitative PCR (qPCR). Furthermore, the relationship between NRP1 and the clinicopathological parameters was investigated. RESULTS: NRP1 staining was limited within normal tissues of the oesophagus, while it was prominent in tumour cells and vasculature. Overexpression of NRP1 receptors (3.6 ± 0.48-folds) was apparent in 81.7% specimens (n = 60, P = 0.0001). qPCR consistently revealed parallel NRP1-mRNA overexpression (3.7 ± 3.7-folds) (n = 16, P = 0.02). A higher molecular weight-modified NRP1 (mNRP1) species was identified in a large proportion of the tumour specimens (85%), accounting for 71.51 ± 20.6% of their total NRP1. Overexpression of tumour NRP1 was positively correlated with deeper invasion into the oesophageal wall (P = 0.05) though mNRP1-positive tumour populations were significantly associated with less lymph node metastasis (P = 0.036) and better prognostic tumour-node-metastasis stage (P = 0.037) than mNRP1 negative tumours. CONCLUSIONS: NRP1 overexpression in oesophageal SCC may contribute to local tumour invasiveness but the presence of the mNRP1 subtype correlates with less lymph node metastasis and better prognostic stage, suggesting that the balance between modified and unmodified NRP1 might be important for determining invasion potential. © The Author 2013. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.