Expression And Pathological Significance Of C-fos, MMP13 In Human Oral Squamous Cell Carcinoma

c-fos is one of the intranuclear oncogenes. Being the early transcription active factor, it can participate in many genic transcription regulation and control cell proliferation and differentiation. The matrix metalloproteinase 13(MMP13) is one of the matrix metalloproteinase family members. Its function is to degrade basement membrane (BM) and extracellular matrix (ECM),then promote invasion and metastasis. Until now, the researches of c-fos and MMP13 in oral squamous cell carcinoma(OSCC) are few. Therefore, we analyzed each target tissue of OSCC , para-OSCC and normal oral squamous epithelium to make clear the mechanism of c-fos and MMP13 in initiation, invasion and metastasis of OSCC.Objectives: In the present study, we undertook immunohistochemical detection of c-fos and MMP13 in OSCC, para-OSCC and normal oral squamous epithelium and compared the expression of both proteins with pathological factors in OSCC, as well as their correlation.Methods: The specimens used by immunohistochemical method were surgically removed from 49 patients with OSCC (well-differentiated OSCC 19 cases, moderately differentiated OSCC 12 cases, poorly differentiated OSCC 18 cases), 20 patients with para-OSCC and 8 people with normal oral squamous epithelium at the First and Second Affiliated Hospital of Dalian Medical University between 2003-2006. Sections with 4μm in thickness were prepared. We detected c-fos protein and MMP13 protein in OSCC, para-OSCC and normal oral squamous epithelium by the Second ElivisionTM plus immunohistochemical method. Rabbit anti-human c-fos polyclonal antibody(ready-to-use) is bought from Fujian Maixin Company. Mouse anti-human MMP13 monoclonal antibody (ready-to-use) is bought from Beijing Zhongshan Company. The results were indicated by the percentage of positive cells counted. The percentage of positive cells in each case was semiquantitatively evaluated. Chi-squared test and Fisher's Exact Test were used to solve the data. McNemar Test and Pearson correlation test was determined between c-fos protein and MMP13 protein expression. All statistical analysis was performed with SPSS 12.0 software package. The probability of p<0.05 was regarded as statistically significant.Results: c-fos intense expression was observed in OSCC and the epithelium of para-OSCC. It was mostly localized in the nucleus of the cell. Strongly-stained cells were distributed in the basal cell layer. Least expression was shown in normal oral squamous epithelium. The expression level of c-fos in OSCCS(67.3%) and para- OSCCS(65%) were apparently higher than normal oral squamous epitheliums (12.5%) (p<0.05). No significant difference was found in c-fos expression between OSCC and para-OSCC(p>0.05). The expression level of c-fos were 84.2%, 75% and 44.4% in well-differentiated, moderately differentiated and poorly differentiated OSCCS, respectively. Positive correlation was found between c-fos expression and OSCC differentiation(p<0.05). No significant correlation was observed between c-fos expression and lymph node metastasis(p>0.05).MMP13 cytoplasmic expression could be recognized in most OSCCS and less the epithelium of para-OSCCS. Strongly-stained cells were distributed in the basal and spinous cell layers of OSCC. No expression was shown in normal oral squamous epithelium. The expression level of MMP13 in OSCCS(63.3%) was apparently high, compared with para-OSCCS(10%) and normal controls(0%)(p<0.01). The expre- ssion level of MMP13 were 42.1%, 66.7% and 83.3% in well-differentiated, moderately differentiated and poorly differentiated OSCCS, respectively. Inverse correlation was found between MMP13 cytoplasmic expression and OSCC differentiation((p<0.05). The positive expression of MMP13 increased significantly comparing to lymph node metastasis(p<0.05). However, no significant correlation was found between c-fos and MMP13 expressions.Conclusions: c-fos nuclear expression was observed in the basal cell layer of OSCC and para-OSCC, and related with OSCC differentiation. Therefore, it's presumed that c-fos was an early event of oral squamous cell carcinogenesis. The over-expression of c-fos had some relations with degree of OSCC differentiation. Furthermore, c-fos could be an index to grade OSCC.MMP13 associates with differentiation, metastasis and prognosis of OSCC. And it could be regarded as the biological marker of OSCC differentiation. The MMP13 expression level in OSCC was negatively correlated with the histological grade, and positively correlated with invasion and metastasis. MMP13 might be a potential marker as a predictor of biological behavior and diagnosis in OSCC for clinician and pathologist.No correlation was found between c-fos protein and MMP13 protein expressions in OSCC.