Lymphangiogenesis markers in metastatic lymph nodes of oral squamous cell carcinoma

• Main Authors: Hussaini, Haizal, Ibrahim, Nurul Ruziantee, Seo, Benedict, Zain, Rosnah, Rich, Alison
• Format: Article
• Language: English; English
• Published: 2019
• Subjects: RK Dentistry
• Online Access: http://irep.iium.edu.my/98506/1/OOOO%202019.pdf; http://irep.iium.edu.my/98506/2/OOOO_2019.png; http://irep.iium.edu.my/98506/; https://www.oooojournal.net/article/S2212-4403(19)30304-9/pdf; https://doi.org/10.1016/j.oooo.2019.02.170

Regional lymph node metastasis is a crucial negative prog- nostic factor in oral squamous cell carcinoma (OSCC). Whilst angiogenic and lymphangiogenic factors have been extensively investigated in primary OSCC, their expression in metastatic lymph nodes remains uncertain. Objectives: To investigate the expression of markers associated with lymphangiogenesis [vascular endothelial growth factor (VEGF)-C, D, VEGF receptor 3 (VEGFR3) and prospero homeobox 1 protein (PROX1)] in cervical lymph nodes from OSCC patients with and without metastatic deposits. Formalin- fixed paraffin-embedded (FFPE) blocks were accessioned from the Oral Cancer Research Coordinating Centre (OCRCC), Uni- versity of Malaya, Malaysia. Samples were divided into two groups; Group A comprised cervical lymph nodes with histologi- cally confirmed metastatic deposits from primary OSCC (n=17) and Group B, cervical lymph nodes from patients with primary OSCC without metastatic deposits, (n=17). Immunohistochemis- try (IHC) was undertaken with antibodies against VEGFC, VEGF-D, VEGFR3 and PROX1. Quantitative analysis using ImageJ was used to delineate the extent of positivity (proportion and intensity) and lymphatic vessel density (LVD). Three sam- ples from each group were subsequently selected for gene expression analysis of the lymphangiogenic markers (VEGFC, VEGFD, VEGFR3 and PROX) using qPCR. Findings: IHC showed significantly greater VEGFC expression in Group A compared with Group B (p=0.0002). Sig- nificant positive correlation was found between VEGFC and TNM stage (p=0.004). No statistically significant differences were observed in the protein and gene expression level of the other tested markers. Conclusions: This is the first study demonstrating sig- nificant overexpression of VEGFC in positive lymph nodes and suggests that VEGFC is an important growth factor involved in OSCC lymph node metastasis.