The clinical values of methylation status of P16 and APC genes in bile in diagnosis of malignant obstructive jaundice.

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171 Background: Preoperative definitive diagnosis of malignant obstructive jaundice caused by biliary and pancreatic carcinomas still remains a major challenge. Hypermethylation of tumor suppressor genes have been implied in carcinogenesis of biliary and pancreatic malignancies. The diagnostic values of methylation status of tumor suppressor genes in bile in malignant obstructive jaundice have not been well-documented. Methods: Bile was prospectively collected from 70 patients with obstructive jaundice treated at our hospital between November 2008 and Sepetember 2009. Forty-eight of them were proved to be malignant obstructive jaundice (biliary carcinoma in 36, pancreatic carcinoma in 8 and duodenal carcinoma in 4) by pathological examination, and 22 were benign obstructive jaundice caused by cholelithiasis. DNA was extracted from bile and modified by sodium bisulfite. Methylation-specific PCR was run to detect methylation status of P16 and APC gene promoters. Their diagnostic values in malignant obstructive jaundice were assessed. Results: Hypermethylation of P16 promoter was presented in 72.9% (35/48) malignant obstructive jaundice, and 9% (2/22) bengin obstructive jaundice (p<0.05). Hypermethylation of APC promoter was presented in 56.2% (27/48) malignant obstructive jaundice, and 9% (2/22) bengin obstructive jaundice (p<0.05). With respect to their diagnostic values in malignant obstructive jaundice, sensitivity, specificity, positive predictivity and negative predictivity were 72.9%, 90.9%, 94.6% and 60.6%, respectively, for P16 gene; 56.2%, 90.9%, 93.1%, 48.8%, respectively, for APC gene. Conclusions: Methylation status of P16 and APC gene promoters in bile was valuable in diagnosis of malignant obstructive jaundice, with an excellent specificity. P16 gene had a higher sensitivity than APC gene. No significant financial relationships to disclose.