Epigenetic Regulation of BCL2-Associated X Protein in Neuroendocrine Lung Tumors
Ihab Lamzabi, Richa Jain, Lela Buckingham, Pincas Bitterman, Vijaya B Reddy, Marta Batus, Paolo Gattuso. Rush University Medical Center, Chicago, IL
Background: The antiapoptotic protein, Bcl2, and it antagonist proapototic, BCL2-Associated X Protein or Bax have been studied in neuroendocrine lung tumors showing that small cell carcinoma of the lung (SCLC) have increased expression of Bcl2, and less expression Bax, than carcinoid tumors (CT). The following study was undertaken to compare epigenetic down-regulation of BAX in both carcinoid tumors and small cell tumors of the lung.
Design: Formalin fixed paraffin embedded tissues from 103 cases of primary lung neuroendocrine lung tumors including 89 small cell carcinomas of the lung, 11 typical carcinoids (TC) and three atypical carcinoids (AC) were used for this study. DNA extracted from microdissected tumor tissue was treated with sodium bisulfite and amplified by PCR using primers to the BAX gene promoter, followed by pyrosequencing. Percent methylation of the BAX promoter region was compared between SCLC and carcinoid tumors. Data was analyzed by the independent samples T-test using SPSS statistical software.
Results: BAX methylation ranged from 3 to 24% in TC, 2 to 7% in AC, and 0 to 19% in SCLC. The average methylation level was lower in SCLC (7.44%) than in TC (10.45%) (p=0.118) and the average methylation level in AC (5%) was lower than in the TC (P=0.156).
Conclusions: Small cell carcinoma of the lung has lower BAX promoter methylation than carcinoid tumors which would predict a higher expression of this pro-apoptotic protein coded by BAX gene. These findings are in contrast to previous observations of lower expression of Bax protein in SCLC compared to AC and TC. Thus, these studies do not support epigenetic control of BAX as a significant regulatory mechanism in these tumors. More studies are needed to better understand the regulation of the apoptotic pathway of small cell carcinoma which is a promising era for better chemotherapeutic agents.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 290, Monday Morning