The Expression And Clinicopathological Significance Of MUC4, EGFR And P-AKT In Cervical Squamous Cell Carcinoma

Background: Cervical cancer is one of the most common causes of morbidity which is responsible for gynecologic malignancies worldwide. Due to the cervical cytology screening programs and HPV vaccination programs, most of the patients were diagnosed and received timely treatment. However, there were still many patients diagnosed advanced cancer. The study about the drugs for cervical cancer has a long way to go. Recently, it has been noted that MUC4, a membrane-bound mucin, is abnormally expressed in several different malignancies, including cervical cancer. However, it was needed further study to reveal the role which MUC4 played in cervical cancer.Objective: We aimed to investigate the expression of MUC4, EGFR and p-AKT in cervical cancer and the interactions among the three markers.Methods: MUC4, EGFR, and p-AKT expression were analyzed in 42 samples of cervical squamous cell carcinoma, 20 samples of high-grade cervical intraepithelial neoplasia(HGCIN), and 20 samples of normal tissues by immunohistochemistry. The protein expression rates were analyzed with Chi-squared test, Fisher's exact tests and Spearman rank correlation by the means of SPSS20.0 software. Western blot was used to detected the protein expression of MUC4, EGFR and p-AKT in normal tissue and cervical cancer. The data was analyzed by independent t-test of SPSS20.0 software.Results: Epithelial cells from cervical cancer, high-grade CIN, and normal tissue epithelial cells expressed MUC4 in 85.7%, 65.0%, and 20.0% of patients, respectively. EGFR was expressed in 71.4%, 65.0%, and 30.0% of patients, respectively. Groups of cervical SCC and HGCIN had significant differences with the group of normal tissue(P<0.05). Western blot revealed that MUC4, EGFR and p-AKT were upregulated obviously in cervical SCC compared with normal tissue. No significant association between MUC4, EGFR, p-AKT expression and various clinicopathological parameters was observed in cervical SCC(P>0.05). In high-grade CIN specimens, the expression of MUC4 was positively correlated with the expression of EGFR. In SCC cervical cancer and high-grade CIN specimens, the expression of MUC4 was positively correlated with the expression of p-AKT.Conclusions:Comparing with normal tissue, MUC4, EGFR and p-AKT were significantly upregulated in cervical SCC and high-grade CIN, which implied that MUC4 could be a possible marker of cervical cancer and high-grade CIN. MUC4 may play roles in the development of cervical SCC through activating EGFR and the following PI3K/AKT pathway.