The neuropilins and their ligands in hematogenous metastasis from salivary adenoid cystic carcinoma - an immunohistochemical study

Publication date: Available online 7 September 2017
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Qianwei Ni, Jinlong Sun, Chao Ma, Yun Li, Jun Ju, Moyi Sun
PurposeTo investigate the expression of neuropilin-1 (NRP1), neuropilin-2 (NRP2), vascular endothelial growth factor-A (VEGF-A), semaphorin-3A (Sema-3A) and semaphorin-3F (Sema-3F) in normal salivary gland (NSG) tissue, non-metastatic salivary adenoid cystic carcinoma (SACC) and metastatic SACC to better understand their role in intratumoral angiogenesis and hematogenous metastasis of SACC.MethodsThe study comprised 60 SACC patients, equally divided between non-metastatic SACC and metastatic SACC. Thirty NSG samples were used as control. Expression of cytokines were studied by immunohistochemistry and compared using integrated optical density (IOD). Relationship between NRP1, NRP2, VEGF-A, and Sema-3A expression and micro-vessel density (MVD) was analyzed in the three groups.ResultsIn metastatic SACC, the expression levels of NRP1 and VEGF-A were significantly higher than in non-metastatic SACC and NSG, while the expression of Sema-3A and Sema-3F was significantly lower than in non-metastatic SACC and NSG (p<0.0001). There were no significant differences in NRP2 expression among the three groups (p=0.43). The MVD of metastatic SACC was significantly higher than that of non-metastatic SACC and NSG (p<0.0001), while the lymphatic vessel density (LVD) of the three groups was not statistically different. The relationship between MVD and NRP1 or VEGF-A showed a significant positive correlation (p<0.0001 for both), while there was a significant negative correlation between MVD and Sema-3A or Sema-3F (p<0.0001 for both).ConclusionHematogenous metastasis of SACC is correlated with high expression of NRP1 and VEGF-A and low expression of Sema-3A and Sema-3F. The increased number of microvessels induced by VEGF-A signaling combined with NRP1 may be one of the key reasons leading to enhanced hematogenous metastasis in SACC.



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