Promoter Methylation and Response to Chemotherapy and Radiation in Esophageal Cancer

James P. Hamilton, Fumiaki Sato, Bruce D. Greenwald, Mohan Suntharalingam, Mark J. Krasna, Martin J. Edelman, Austin Doyle, Agnes T. Berki, John M. Abraham, Yuriko Mori, Takatsugu Kan, Carmit Mantzur, Bogdan Paun, Suna Wang, Tetsuo Ito, Zhe Jin, Stephen J. Meltzer

Research output: Contribution to journalArticlepeer-review

69 Scopus citations


Background & Aims: Multiple studies have shown that promoter methylation of tumor suppressor genes underlies esophageal carcinogenesis. Hypothetically, methylation resulting in tumor suppressor gene inactivation might result in tumors that are unresponsive to chemotherapy and radiation. Accordingly, our aim was to find methylation markers that could be used to predict response to chemoradiation. Methods: Tumor specimens were obtained before treatment from 35 patients enrolled in a uniform chemoradiation treatment protocol. Methylation-specific quantitative polymerase chain reaction was performed on all samples. Pathology reports from esophagectomy specimens were used to define response to treatment. Results: Thirteen (37%) of 35 patients were responders, and 22 (63%) of 35 patients were nonresponders. The number of methylated genes per patient was significantly lower in responders than in nonresponders (1.4 vs 2.4 genes per patient; Student t test, P = .026). The combined mean level of promoter methylation of p16, Reprimo, p57, p73, RUNX-3, CHFR, MGMT, TIMP-3, and HPP1 was also lower in responders than in nonresponders (Student t test, P = .003; Mann-Whitney test, P = .001). The frequency (15% of responders vs 64% of nonresponders; Fisher exact test, P = .01) and level (0.078 in responders vs 0.313 in nonresponders; Mann-Whitney test, P = .037) of Reprimo methylation was significantly lower in responders than in nonresponders. Conclusions: Reprimo methylation occurred at significantly lower levels and less frequently in chemoradioresponsive than in nonresponsive esophageal cancer patients, suggesting potential clinical application of this single-gene biomarker in defining prognosis and management. In addition, increased methylation of a 9-gene panel correlated significantly with poor responsiveness to chemoradiation.

Original languageEnglish (US)
Pages (from-to)701-708
Number of pages8
JournalClinical Gastroenterology and Hepatology
Issue number6
StatePublished - Jun 2006
Externally publishedYes

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology


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