Upregulation of Adam10 in Oral Squamous Cell Carcinoma and Its Correlation With Egfr, Neoangiogenesis and Clinicopathologic Factors Publisher Pubmed



Etemadmoghadam S¹ ; Alaeddini M¹ Show Affiliations
Source: Journal of Cranio-Maxillofacial Surgery Published:2019

Abstract

ADAM10 (a disintegrin and metalloproteinase-10) is a known sheddase for EGFR (epidermal growth factor receptor) ligands and has been suggested to modulate angiogenesis. We aimed to evaluate the expression of ADAM10 in patients with oral squamous cell carcinoma (OSCC) and to determine its correlation with EGFR, CD105 and clinicopathologic parameters. Fifty primary OSCCs with clinical data were graded according to the histologic risk assessment (HRA) model and subjected to immunohistochemical staining using antibodies against ADAM10, EGFR1 and CD105. ADAM10 was assessed in both epithelial and stromal components. The associations among all three proteins and clinicopathologic factors including tumor size, lymph node status and distant metastasis (TNM) were statistically analyzed (P < 0.05). Epithelial-ADAM10, stromal-ADAM10 and EGFR were overexpressed in 92%, 40% and 56% of the OSCCs, respectively. EGFR expression occurred in peripheral and diffuse patterns, which were also separately considered in our analyses. A significant correlation was found between ADAM10 and CD105 (r = −0.455; P < 0.001). Lymphocytic infiltration scores (P = 0.04) and tumor size (P = 0.001) showed significant differences between EGFR+ and EGFR− tumors, but none of the other variables had any relationships with either clinicopathologic factors or each other (P > 0.05). ADAM10 was upregulated in OSCC but had no correlation with survival-associated factors such as TNM or the HRA model. At the protein level, epithelial ADAM10 negatively regulated neoangiogenesis, but its interaction with EGFR was minimal. Reduction in host immunologic responses was associated with a decrease in EGFR. These findings, if corroborated, could be interesting in combination therapies used for cancer treatment. © 2019 European Association for Cranio-Maxillo-Facial Surgery