臨床および実験腫瘍学ジャーナル

Promoter Methylation and Loss of Expression of PTEN Gene in Breast Cancer Patients from Saudi Population

Mohammad Shabbir Alam*, Ahmed Bin Ali Jerah, Jalaluddin Mohammad Ashraf, Kathamuthu Kumaresan, Zaki Monawar Eisa and Nabil Tadros Mikhail

Objective: PTEN, a tumor-suppressor gene, located on chromosome 10q23.3, is implicated in various types of cancer including breast cancer. The aim of this study is to investigate the promoter methylation, loss of expression and significance of PTEN gene in breast cancer and to determine the correlation between promoter methylation and gene expression.

Methods: Promoter methylation and loss of expression of PTEN gene were analyzed using methylation-specific PCR and immunohistochemical methods respectively. The chi square test is used to correlate the promoter methylation and gene expression with their clincopathologic parameters.

Results: We examined 53 breast cancer specimens and 10 normal tissues adjacent to tumor. The results showed a 58.5% promoter methylation in PTEN gene and none in normal tissue. PTEN methylation was observed in advanced stages III-IV (81.8%, 18 of 22, P=0.015) and higher grades G2-G3 (71.4%, 20 of 28, P=0.043) of disease. The correlation of PTEN methylation with clinical stage and tumor grade was found to be statistically significant. Nuclear PTEN expression was detected in 73.6% (39 of 53) cases of breast cancer and in the remaining 26.4% (14 of 53) cases expressional loss was observed. The loss of PTEN expression was observed in all normal tissues (10 of 10). The loss of PTEN expression was significantly correlated with patient’s age (P=0.028) and clinical stage (P = 0.029). The expressional loss was observed in 12 (38.7%) cases among 31 methylation positive cases, whereas among 22 methylation- negative cases, only 2 (9.1%) cases were seen as immunostaining negative with the statistically significant value (P=0.016).

Conclusion: Promoter methylation and loss of expression of PTEN gene occur frequently in breast cancer. Our results suggest that PTEN plays an important role in breast carcinogenesis.