Expression Of Gli1 And The Correlation With Expression Of PCNA And Tumor Angiogenesis Im Laryngeal Squamous Cell Carcinomas

Objective: Laryngeal squamous carcinoma is one of the most common malignant neoplasms in the head and neck region, accounting for 13.9% of all malignant neoplasms in the head and neck region. Investigation about the mechanisms of the carcinogenesis, growth and metastasis of laryngocarcinoma are warm spots in head and neck cancer research. This is also significant for early diagnosis or gene therapy. Many studies have demonstrated that some signal transduction pathways activated in embryo stem cells such as the Hedgehog (Hh) signal pathway, required for patterning of the early embryo and regulates segment polarity and wing and limb growth, have been reactivated in many tumors and play important roles in the carcinogenesis, growth and metastasis. Gli1 is a sort of nucleur transcription factor of Hedgehog (Hh) signal pathway which is expressed higher in basal cell carcinoma, gastric cancer, small cell lung cancer, skin squamous cell carcinoma, cervix cancer and so on. The expression of Gli1 in these cancers is associated with their low differentiation and high invasiveness. However, there are few reports about expression of Gli1 in laryngeal squamous carcinomas, and the role of Gli1 expression in the carcinogenesis and metastasis in laryngeal squmous carcinoma is largely unknown. In this paper we investigated the expression of Gli1, PCNA, and CD34 in laryngeal squmous carcinoma by immunohistochemistry and analyze the relationship between them and the relevance with clinicopathological parameters of patients, so as to provide a new diagnostic and therapeutic target in laryngeal squmous carcinoma.Methods: 40 cases of surgically resected laryngeal carcinoma specimens and 10 cases of paracancerous laryngeal mucosa, which were recruited from Department of Otorhinolaryngology Head and Neck Surgery, Bethune International Peace Hospital were used. The patients had received neither chemotherapy nor radiation therapy before tumor resection. Immunohistochemical staining (S-P methods) for the paraffin sections were used to detected the expression of Gli1, PCNA and CD34 in 40 laryngeal squamous cell carcinoma tissues and 10 paracancerous laryngeal tissues. Microvessel density (MVD) was calculated. Using statistical analysis, we analyzed the correlation of the Gli1expression with the expression of PCNA, MVD and clinicopathological factors.Results: 1. Using immunohistochemistry, we found the expression of Gli1 in the 40 cases of laryngeal squamous cell carcinoma were robust and the immunoreactive score (IS) was 4.60±3.52. We also found that the expression of Gli1 in the 10 cases paracancerous laryngeal mucosa was lower, and the immunoreactive score (IS) was 1.50±0.70. Comparison of expressions of Gli1 in paracancerous laryngeal mucosa and in the laryngeal squamous cell carcinoma, we found that there was significant difference between the two group (p <0.01). 2. The expression of Gli1 in the 40 cases laryngeal squamous cell carcinoma was significantly related to pathologic grade (p =0.000) and lymphatic metastasis (p=0.001), but had no relation to the element such as age (p=0.572), sex (p=0.837), tumor site (p=0.947) and tumor T stage (p=0.560). 3. Using immunohistochemistry, we found the expression of PCNA in laryngeal squamous cell carcinoma were more widespread compared with that in paracancerous laryngeal mucosa. The expression of PCNA in the 40 cases laryngeal squamous cell carcinoma were significantly related to pathologic grade (p=0.012) and lymphatic metastasis(p=0.000), but had no relation to tumor T stage(p=0.157). 4. Gli1 protein expression and PCNA protein expression in laryngeal squamous cell carcinoma were positively correlated (r=-0.487,p<0.001). 5. MVD in lymphatic metastasis group was strikingly higher than that in no lymphatic metastasis group of laryngeal squamous cell carcinoma. Gli1 protein expression and MVD in laryngeal squamous cell carcinoma were positively correlated (r=0.541, p=0.000).Conclusions: 1. The Gli1 protein was omni-expressed in laryngeal squamous cell carcinoma, but the Gli1 protein expression was lower in all paracancerous laryngeal mucosa. 2. The expression of Gli1 protein was not related to patients'age, sex, T-stage and tumor position, but related to cell differentiation level and lymph node metastasis. 3. The expression of PCNA in laryngeal squamous cell carcinoma was more widespread compared with that in paracancerous laryngeal mucosa. The expression of PCNA protein was not related to patients'T stage, but related to cell differentiation level and lymph node metastasis. 4. Correlation analysis demonstrated a significant positive relationship between the expression of Gli1 and the expression of PCNA in laryngeal squamous cell carcinoma, which suggested that the expression of Gli1 facilitated cell growth of laryngeal squamous cell carcinoma. 5. Correlation analysis demonstrated a significant positive relationship between the expression of Gli1 and MVD in laryngeal squamous cell carcinoma, which suggested that the expression of Gli1 increased the possibility of tumor invasiveness and metastasis of laryngeal squamous cell carcinoma.