الفهرس 
Carcinoma-associated fibroblastsOnly 14 pages are availabe for public view
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Abstract
OSCC is a malignant neoplasm derived from the stratified squamous epithelium of the oral mucosa. It occurs at various sites, the most frequent being the lip, lateral edges of the tongue and floor of the oral cavity. The incidence of OSCC increases with age, with the majority of OSCC occuring in patients >40 years. At the time of diagnosis, the majority of patients present advanced disease stages and approximately one third of them show LNM. Despite the currently available therapeutic strategies, which include the excision of malignant tissue and combination of radiotherapy and chemotherapy, the five-year survival rate is only 50%. In addition, a high percentage of patients have a poor response to therapy and high recurrence rates.
CD10 is a cell surface zinc-dependent endopeptidase, which is expressed in different cell types and degrades many bioactive peptides. It may also play an important role in maintenance of homeostasis, neoplastic transformation and tumor progression. CD10 may have a specific role in controlling cell growth and differentiation of both hematopoietic and epithelial cell groups, its expression is increased in malignant tumors and regenerating tissues. It was proposed that CD10 is involved in both proliferation and apoptosis when expressed in cancer cells, while its stromal expression may cause tumor progression. Moreover, there are cumulative data indicating that CD10 expression by stromal cells is involved in carcinogenesis and is supposed to be a novel prognostic factor in some malignant neoplasms.MMP-2 is the most widely distributed member of MMPs, which cleaves type IV collagen, the main component of BM. The ability of MMP-2 to initiate BM destruction and further degradation of ECM suggests its importance in tumor invasion and metastasis. Stromal cells typically synthesize MMP-2, which can then act on the stroma and regulate the TME as well as the tumor cells themselves. MMP-2 has been associated with cancer cells invasion, proliferation, angiogenesis, EMT and immune surveillance. Many studies have proposed that MMP-2 may serve as a novel biomarker for tumor progression and invasion in various malignant lesions.
This study was conducted to immunohistochemically evaluate the stromal expression of CD10 and MMP-2 in different grades of OSCC and to detect if a correlation existed between both markers in OSCC grades as well as with LN involvement.
Twenty-five formalin-fixed paraffin-embedded specimens of OSCC with three different histopathological grades were used in this study. Eight cases were diagnosed as well diff., nine diagnosed as mod. diff. and eight cases were diagnosed as poorly diff. OSCC, in addition to five specimens of normal oral mucosa. Immunohistochemical staining using the biotin-streptavidin immunoperoxidase technique was performed with CD10 and MMP-2. The immunostained slides were examined by light microscopy and photographed. The photographs were then analyzed using image analysis software. For all cases, the area fraction of immunopositivity for four different microscopic fields was measured. The MAF for each case was then calculated and used for statistical analysis.Immunohistochemical results of the present study revealed that the MAF of CD10 immunopositivity became higher as the grade increased from well to mod. to poorly diff. OSCC and the same results were detected for MMP-2.
The Tukey pair-wise test revealed a statistically significant difference between different grades of OSCC for CD10 and MMP-2. In addition, statistical results of Pearson’s correlation study showed a significant strong direct correlation between CD10 and MMP-2 in different grades of OSCC (R- value = 0.796) (p value < 0.001). Logistic regression analysis revealed that stromal MMP-2 could be used as an independent predictor for LNM in OSCC.
Based upon these data, it could be concluded that CD10 and MMP-2 could be used as valuable prognostic markers for loss of differentiation of OSCC. In addition, according to the difference in MAF between different grades, CD10 and MMP-2 could be used as useful indicators that could help to stratify OSCC grades.
CD10 and MMP-2 expression increased with higher grades, thus the over-expression of CD10 and MMP-2 in combination could be used for predicting poor prognosis in patients with OSCC and this may be more significant than using a single marker.