Study On 10q23 LOH And Both Mutation And Expression Of PTEN Gene Of The Oesophageal Squamous Cell Carcinomas In Chinese Population

Objective: To explore the significance of the loss of heterozygous (LOH), microsatellite instability (MSI) on 10q23. 3 and the tumor- suppressor gene PTEN (phosphatase and tensin homologue deleted on chromosome 10) in the carcinogenesis of human oesophageal squamous cell carcinoma in Chinese population. Methods: Matched 24 pairs normal and tumor samples were collected from who underwent surgery for oesophageal squamous cell carcinoma. Genomic DNA was extracted frome selected fresh tissues .Microsatellite markers D10S215, D10S541 , D10S551 and D10S2491 have been used to perform PCR-PAGE-silver staining for allelic imbalance (AI). All samples were screened for mutations in exons 4, 5, 6, 7 and 8 of PTEN gene by PCR-SSCP analysis. Expression levels of PTEN gene were detected by the SP immunohistochemical technique in the selected 24 pairs of tumor tissues and the related normal tissues. Results: In this study we found that the positive frequency of LOH in 10q23 was 29.2% (7/24) , and that of MSI and AI were 8. 3% (2/24) and 37. 5% (9/24) in oesophageal squamous cell carcinoma tissues of Chinese population respectively.10q23 LOH and MSI had no significant correlation with both tumor TNM stage and lymph node metastasis (P>0. 05). We did not find mutations in the exons 4 to 8 of the PTEN gene by using PCR-SSCP analysis. SP immunohistochemistry analysis indicated that PTEN gene was mainly expressed in cytoplasm. There was no statistically significant correlation on the expressional level between the oesophageal squamous cell carcinoma tissues and the related normal tissues in the collected 24-pair samples (P>0.05). Meanwhile there was no statistically significant correlation between the expressional intensity of PTEN protein in oesophageal squamous cell carcinoma and the TNM stage (P>0. 05) of the tumor. The expressional intensity of PTEN protein in lymph node metastasis positive samples is marked lower than that of it in lymph node metastasis negative samples. There was high correlation between the expressional intensity of PTEN protein and lymph node metastasis (P<0.05). Conclusions: In this study, the presence of LOH and MSI on 10q23 are not significantly associated with the tumor TNM stage and lymph node metastasis of oesophageal carcinomas. However, other tumor suppressor genes at 10q23 may be involved in the carcinogenesis of human oesophageal squamous cell carcinoma in Chinese population. Mutations of PTEN gene do not play a major role in the carcinogenesis of oesophageal squamous cell carcinoma. There is no statistically significant correlation between the expressional intensity of PTEN protein inoesophageal squamous cell carcinoma and the TNM stage of the tumor, but is associated with the lymph node metastasis. PTEN expression is marked down-regulated in the tumor tissue of the oesophageal squamous cell carcinoma patient with lymph node metastasis. Thus, the lower expressional level of PTEN protein may be a significant risk factor for lymph node metastasis in oesophageal squamous cell carcinoma patients.