Peri-tumoral Lymphovascular density by antipodoplanin antibody D2-40, as a predictor of nodal metastasis in oral squamous cell carcinoma

Abstract

BACKGROUND: The involvement of regional lymph nodes by cancer is a major determinant of prognosis in oral squamous cell carcinoma (OSCC) and is a significant predictor of patient survival. Peri-tumoral lymphangiogenesis is being studied as an important tool in predicting neck lymph node metastasis. Podoplanin, a transmembrane glycoprotein is expressed on lymphatic vessel endothelium and considered as a marker of lymphangiogenesis.  The high podoplanin expression has been associated with invasion, progression, and metastasis of oral cancer. D2-40, an anti-podoplanin monoclonal antibody, is a specific marker of lymphatic endothelial cells. The present study was designed to investigate the peritumoral lymphovascular density (PT-LVD) by evaluating D2-40 expression and its potential utility in predicting lymph node metastasis in OSCC. METHODS: Seventy-two patients with OSCC were enrolled (36 with early and 36 with advanced-stage tumors). Differential expression of peritumoral lymphovascular density (PT-LVD) was evaluated using D2-40 expression by immunohistochemistry (IHC). Expression was categorized as low and high, derived from the mean of a number of vessels per 10 high power fields in hot-spots. Statistical methods were employed to correlate expression with age, gender, tumor site, stage, and neck lymph node involvement.  RESULTS: We observed a significant association between peritumoral lymphovascular density (PT-LVD) with clinical neck lymph node status (p=0.001) and tumor stage (p=0.033).  There was no significant correlation of D2-40 expression with age, gender, tumor site, T stage, and tumor differentiation. CONCLUSION:  PT-LVD is a positive predictor of neck lymph node metastasis. It has translational potential, along with other clinical parameters for decision making in the treatment of the neck in oral cancer.