Expression of CD44 (NKI-P1) in oral squamous cell carcinoma associated vascular endothelial cells: A relationship to tumor angiogenesis

Background: Oral squamous cell carcinoma is characterized by high degree of local invasion with metastasis as well as characteristic angiogenic features. Angiogenesis is a critical step in the growth and metastasis of tumors. Cluster of differentiation 44 (CD44) is a cell surface glycoprotein which is widely expressed in both physiological and pathological conditions.

Aim: The study was designed to assess the expression of CD44 (NKI-P1) in oral squamous cell carcinoma associated endothelial cells and to correlate this expression with matrix metalloprpteinase-9 (MMP-9) and transforming growth factor-beta (TGF- β) expression immunohistochemically.

Materials and methods: One hundred fourteen archival oral squamous cell carcinoma cases were used in this study. Immunohistochemistry was performed for CD44 (NKI-P1), Ki-67, cluster of differentiation 31(CD31), podoplanin (D2-40), MMP-9 and TGF- β. Microvessel density was also determined morphologically. Results: CD44 was expressed in (CD31+/ Podoplanin -) blood vascular endothelial cells in a strong cytoplasmic fashion. In addition, the extracellular matrix proteins (MMP-9 and TGF-β were expressed in oral squamous cell carcinoma stroma which was enriched with CD44 + blood vessels. The mean numbers of microvessel density in connective tissue beneath normal epithelium and different grades of oral squamous cell carcinoma stroma were 5.8, 22.1, 22.4 and 23.5, respectively with the P-value < 0.05, where a significant statistical difference between microvessel density in the connective tissue beneath normal epithelia and stroma of all grades of oral squamous cell carcinoma was found. Conclusion: CD44 (NKI-P1) is considered a potential marker of oral squamous cell carcinoma angiogenesis and it can be used as a valuable biomarker of tumor invasion and as a therapeutic target for anti-angiogenic therapies.