الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Oral squamous cell carcinoma (OSCC) accounts for more than 90% of all oral cancers. Less than 40% of the OSCC patients who present nodal involvement survive after five years, compared to a 90% survival rate for patients without metastasis. The prognosis of OSCC remains unfavorable, notwithstanding advances in diagnosis and therapy. If the lesion is detected at an early stage and treated effectively, the 5-year survival rates of OSCC patients could exceed 50%. Therefore, an understanding of the molecular mechanisms involved in OSCC progression would be helpful to attain early detection and develop more effective treatments.
Within tumors, Interactions between cancer cells and the stromal compartment have major impact on cancer growth and progression. Myofibroblasts are the most prominent stromal cell type in tumor microenvironment. Cytokines secreted from cancerous cells such as TGF-β1 promote differentiation of fibroblasts into myofibroblasts where the stroma changes from normal to “activated” or “tumor associated. Myofibroblasts are hybrid phenotype cells with fibroblast and smooth muscle tissue characteristics. They are large spindle-shaped cells with stress fibers and well-developed fibro-nexus. The presence of myofibroblasts has been reported in the stroma of various type of cancers. Myofibroblasts or cancer associated fibroblasts secrete several enzymes and growth factors that promote tumor growth, invasion, and metastasis. Many studies suggest that myofibroblastic CAFs may be used as a predictive marker for LN metastasis.
Alpha-smooth muscle actin (α-SMA) is regarded as the most widely used biomarker for identifying myofibroblastic CAFs. However, it cannot differentiate them from smooth muscle cells.
The role of myofibroblasts have been illustrated in many cancers. However, it is not sufficiently studied in oral cancer particularly correlation with lymph node metastasis.
The aim of the present work was to assess the presence and distribution patterns of myofibroblasts in OSCC according to histological grade, as well as to determine its correlation with regional lymph node metastasis. This was done using α-SMA antibody.
In the present study, a total of 30 patients with OSCC were included. Oral SCC cases were further sub-classified into 2 study groups. Fifteen cases (50%) were proved histologically to be associated with positive lymph node metastasis, while the other 15 were associated with lymph node free.
Their age ranged between 38 and 74 years. Fifteen patients (50%) were males and 15 (50%) were females.
The most common site of occurrence of OSCC was the lateral side of the tongue (36.7%), followed by the buccal mucosa (16.7%), alveolar mucosa (13.3%), and the gingiva (10%). Floor of the mouth, lower lip, tip of the tongue, and palate, were equal (6.7% for each). Both ventral surface of the tongue and retro-molar area were the least sites showing OSCC occurrence (3.33% each).
Biopsies were histologically evaluated using Hematoxylin and Eosin (H&E) staining. The microscopical examination revealed that 30% of the cases were well differentiated, 50% were moderately differentiated and 20% of cases were poorly differentiated squamous cell carcinoma.
Serial sections were immunohistochemically stained by monoclonal antibody to α-SMA using Labeled- Strept -Avidin Biotin complex method. The expression of α-SMA was evaluated in terms of percentage of immune-positive stromal cells and immune-staining intensity. Multiplication of the percentage and intensity scores comprised the staining index of each specimen.
The connective tissue stroma of 27 OSCC biopsies were immune positive to α-SMA, while 3 OSCC cases showed negative immunoreactivity in their stroma except endothelial cells lining the blood vessels. The stromal myofibroblasts showed positive immunoreactivity to α-SMA with different intensities.
The difference in the expression of α-SMA among well, moderate and poorly differentiated OSCC, using Chi square test, was statistically non-significant (P = 0.807).
On the other hand, the presence of myofibroblasts was significantly higher in the OSCC with LN metastasis than OSCC without LN metastasis (Post Hoc Test, P = 0.004).
Considering the distribution patterns of stromal myofibroblasts, network and spindle patterns were seen in 60% and 50% of all OSCC cases, respectively. Chi square test revealed that the distribution of myofibroblasts was not significantly different among the three histological grades of oral squamous cell carcinoma (P= 0.704, P= 0.740, P= 0.912).
In addition, the distribution patterns were mainly network (73.3%) and spindle (66.7%) in cases of OSCC with LN metastasis. Meanwhile, focal distribution was the predominant pattern observed in 9 cases (60%) of OSCC without LN metastasis. No significant association was detected between the pattern of Myofibroblasts and the lymph node status (P < 0.05).
The current study concluded that myofibroblasts can be detected immunohistochemically using α-SMA in human tissues of OSCC. The presence of myofibroblasts is significantly correlated with lymph node status. While, there is no significant correlation with the histological grading of OSCC. This would support the possibility of using myofibroblasts as indicator for lymph node metastasis.