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[Cancer Research 62, 371-375, January 15, 2002]
© 2002 American Association for Cancer Research

Advances in Brief

Quantitative Adenomatous Polyposis Coli Promoter Methylation Analysis in Tumor Tissue, Serum, and Plasma DNA of Patients with Lung Cancer1

Henning Usadel, Jan Brabender, Kathy D. Danenberg, Carmen Jerónimo, Susan Harden, James Engles, Peter V. Danenberg, Stephen Yang and David Sidransky2

Departments of Otolaryngology-Head and Neck Surgery, Head and Neck Cancer Research Division [H. U., C. J., S. H., J. E., D. S.] and Thoracic Surgery [S. Y.], Johns Hopkins University School of Medicine, Baltimore Maryland 21205-2196, and Department of Biochemistry and Molecular Biology and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California 90033 [J. B., K. D. D., P. V. D.]

The serum of cancer patients often harbors increased free DNA levels, which can potentially be used for cancer detection. Because genetic and epigenetic alterations of the adenomatous polyposis coli (APC) gene are common events in gastrointestinal tumor development, we sought to investigate the frequency and level of aberrant APC promoter methylation in primary tumors and paired preoperative serum or plasma samples of lung cancer patients by semiquantitative methylation-specific fluorogenic real-time PCR. We detected methylation of APC in 95 of 99 (96%) primary lung cancer tissues. Forty-two of 89 (47%) available serum and/or plasma samples from these cases carried detectable amounts of methylated APC promoter DNA. In contrast, no methylated APC promoter DNA was detected in serum samples from 50 healthy controls. A highly elevated APC methylation level in lung cancer tissue was the only independent factor predicting inferior survival in this cohort (P = 0.015). APC methylation analysis appears to be promising as a prognostic factor in primary lung cancer and as a noninvasive tumor marker in plasma and/or serum DNA.




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