Header

UZH-Logo

Maintenance Infos

Death-associated protein kinase (DAPK) promoter methylation and response to neoadjuvant radiochemotherapy in esophageal cancer


Brabender, J; Arbab, D; Huan, X; Vallböhmer, D; Grimminger, P; Ling, F; Neiss, S; Bollschweiler, E; Schneider, P M; Hölscher, A H; Metzger, R (2009). Death-associated protein kinase (DAPK) promoter methylation and response to neoadjuvant radiochemotherapy in esophageal cancer. Annals of Surgical Oncology, 16(5):1378-1383.

Abstract

BACKGROUND: 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 investigate if aberrant methylation of the apoptosis-related gene Death-Associated Protein Kinase (DAPK) could be used as a predictor of response to neoadjuvant therapy in locally advanced cancer of the esophagus. METHODS: Tumor and normal esophageal tissues were obtained from 50 patients with locally advanced cancer of the esophagus prior to neoadjuvant radiochemotherapy. DAPK methylation analysis was performed on all samples by methylation-specific real-time polymerase chain reaction (PCR). RESULTS: Seventeen (34%) patients showed a major and 33 (66%) a minor histomorphological response to neoadjuvant therapy. DAPK methylation was detectable in normal esophageal tissues with a frequency of 10% and in tumor tissue with a frequency of 78%. The median methylation level for DAPK was 2.7 x 10(-3) in tumor compared with 0.1 x 10(-3) in normal tissues (p < 0.001). DAPK methylation was not associated with response to neoadjuvant therapy or prognosis after esophagectomy. CONCLUSION: Aberrant DAPK methylation in tumor tissues is significantly higher compared with matching normal esophageal tissues, suggesting a fundamental role of this epigenetic alteration in the pathogenesis of this disease. The level of DAPK methylation in pretreatment biopsies of patients with locally advanced cancer of the esophagus is no marker for the prediction of histomorphological regression or prognosis following neoadjuvant chemoradiation in this disease.

Abstract

BACKGROUND: 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 investigate if aberrant methylation of the apoptosis-related gene Death-Associated Protein Kinase (DAPK) could be used as a predictor of response to neoadjuvant therapy in locally advanced cancer of the esophagus. METHODS: Tumor and normal esophageal tissues were obtained from 50 patients with locally advanced cancer of the esophagus prior to neoadjuvant radiochemotherapy. DAPK methylation analysis was performed on all samples by methylation-specific real-time polymerase chain reaction (PCR). RESULTS: Seventeen (34%) patients showed a major and 33 (66%) a minor histomorphological response to neoadjuvant therapy. DAPK methylation was detectable in normal esophageal tissues with a frequency of 10% and in tumor tissue with a frequency of 78%. The median methylation level for DAPK was 2.7 x 10(-3) in tumor compared with 0.1 x 10(-3) in normal tissues (p < 0.001). DAPK methylation was not associated with response to neoadjuvant therapy or prognosis after esophagectomy. CONCLUSION: Aberrant DAPK methylation in tumor tissues is significantly higher compared with matching normal esophageal tissues, suggesting a fundamental role of this epigenetic alteration in the pathogenesis of this disease. The level of DAPK methylation in pretreatment biopsies of patients with locally advanced cancer of the esophagus is no marker for the prediction of histomorphological regression or prognosis following neoadjuvant chemoradiation in this disease.

Statistics

Citations

16 citations in Web of Science®
17 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

0 downloads since deposited on 25 Jan 2010
0 downloads since 12 months

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Visceral and Transplantation Surgery
04 Faculty of Medicine > University Hospital Zurich > Division of Surgical Research
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2009
Deposited On:25 Jan 2010 11:26
Last Modified:05 Apr 2016 13:48
Publisher:Springer
ISSN:1068-9265
Additional Information:The original publication is available at www.springerlink.com
Publisher DOI:https://doi.org/10.1245/s10434-009-0356-1
PubMed ID:19224282

Download

Preview Icon on Download
Filetype: PDF - Registered users only
Size: 1MB
View at publisher

TrendTerms

TrendTerms displays relevant terms of the abstract of this publication and related documents on a map. The terms and their relations were extracted from ZORA using word statistics. Their timelines are taken from ZORA as well. The bubble size of a term is proportional to the number of documents where the term occurs. Red, orange, yellow and green colors are used for terms that occur in the current document; red indicates high interlinkedness of a term with other terms, orange, yellow and green decreasing interlinkedness. Blue is used for terms that have a relation with the terms in this document, but occur in other documents.
You can navigate and zoom the map. Mouse-hovering a term displays its timeline, clicking it yields the associated documents.

Author Collaborations