Expression Of Hedgehog Signaling Molecules And Their Clinical Significance In Tongue Squamous Cell Carcinoma

Tongue squamous cell carcinoma is the most common malignant tumor of the oral and maxillofacial tumors. It fast-growing, invasive, was mainly taken to expand radical surgery and adjuvant radiation therapy. But the treatment is ineffective and has higher recurrence rate and poor prognosis. The development and transfer mechanisms of tongue squamous cell carcinoma are not yet fully elucidated. Generally, the incidence and development of tongue squamous cell carcinoma is closely related to the regulation of signaling proteins system.Hedgehog (Hh) signaling pathway play a role in mammalian embryonic development, histogeny, cell proliferation and migration of germ cells. Its expression is tightly regulated by many factors. Previous studies have shown that the Hh signaling pathway may play an important role in the process of tongue squamous cell carcinoma. Ptch, Smo and Glil protein is an important factor of the Hh signaling pathway. In this comparative study, we detect Hh signaling molecules PTCH, SMO and Glil protein expression between the tongue squamous cell carcinoma and normal tongue mucosa by immunohistochemistry, also analysis of the link between the Hh signaling pathway and tongue squamous cell carcinoma. Looking for appropriate target for treatment of tongue squamous cell carcinoma by molecular methods.Objective:To explore the expression pattern of Hh signaling pathway protein with PTCH, SMO and Glil protein in tongue squamous cell carcinoma by immunohistochemistry, and its potential clinical significance of the intrinsic link. This study further elucidate the molecular mechanisms in the development process of tongue squamous cell carcinoma, and provide a theoretical basis of looking for a new target with molecular methods for diagnosis and treatment of tongue squamous cell carcinoma.Methods:Patients treated for tongue squamous cell carcinoma from2011to2012were identified from the database of the Stomatological Hospital Affiliated Medical School, Nanjing University. A total of24cases of tongue squamous cell carcinoma confirmed by pathology,11cases were male and13female, age34-81years old, with an average age of52.3years old.All tongue squamous cell carcinoma following conditions are met:1complete clinical records;2all patients without radiotherapy, chemotherapy and other special treatment;3routine pathological diagnosis of squamous cell carcinoma of tongue;4all patients underwent resection of the primary tumor and neck lymph node dissection;5cervical lymph node metastasis based on pathological diagnosis. And in accordance with the International Union Against Cancer (UICC)2002years of clinical pathological staging classification. Tongue normal mucosal tissue from the tongue squamous cell carcinoma edge2cm as a control which confirmed by pathology, phosphate-buffered saline (PBS) instead of primary antibody as a negative control. All test specimens were fixed in4%formaldehyde and embedded in paraffin.Statistical analysis used the chi-square test, Fisher’s exact method and Spearman’s rank correlation analysis. All analyses were performed in SPSS18.0. statistical software package and P<0.05was considered indicative of statistically significant.Results:Ptch, Smo, Gli1protein positive expression in squamous cell carcinoma of the tongue. Ptch and Smo are mainly positive of cell nucleus. Ptch protein expression in tongue squamous cell carcinoma was79.1%, in the normal tongue mucosa tissue expression rate was4.2%. Compared with normal tissue, Ptch was high expression in squamous cell carcinoma of the tongue, the difference was high statistically significant (χ2=15.374, P<0.05). Smo protein expression in tongue squamous cell carcinoma was83.3%, negative expression in the tongue mucosa normal tissues.Compared with normal tissue, Smo was high expression in squamous cell carcinoma of the tongue, and the difference was statistically significant (χ2=17.478, P<0.05). Glil protein expression in tongue squamous cell carcinoma was20.1%, in the normal tissue expression rate was4.2%, and the difference was statistically significant (x2=6.835, P<0.05). In the control group (PBS instead of primary antibody),Ptch, Smo and Glil were negative expression.Ptch, Smo, Glil protein expression was not statistically significant with age, sex, alcohol and tobacco habits, lymph node metastasis (P>0.05), but was statistically significant with histological grade and clinical stage (P<0.05). The higher histological grade and clinical staging, the higher protein expression.In tongue squamous cell carcinoma, the higher Ptch and Smo positive expression the higher Glil expression. The Ptch protein and GLI1protein expression was positive correlation by Spearman correlation analysis (r=0.635, P<0.05); Smo protein and Glil protein expression was positive correlation (r=0.724, P<0.05),Ptch protein and Smo protein expression was positive correlation (r=0.586, P<0.05).Conclusions:Excessive activation of the Hh signaling pathway in tongue squamous cell carcinoma. Compared with the normal tongue mucosa tissue, the performance of the Hh signaling pathway components Ptch, Smo and Glil overexpression in tongue squamous cell carcinoma. And the Smo protein mainly as nuclear positive expression. The activation of Smo play a key role in the Hedgehog signaling pathway. In malignancy, the abnormal activation of Smo is a prerequisite for malignant tumor occurrence and development, which we can infer the Hh signaling pathway, especially Smo can be used as a new target for cancer treatment.