Skip to main content
Top
Published in: Journal of Gastrointestinal Surgery 11/2008

01-11-2008 | 2008 ssat plenery presentation

ERCC1 RNA Expression in Peripheral Blood Predicts Minor Histopathological Response to Neoadjuvant Radio-chemotherapy in Patients with Locally Advanced Cancer of the Esophagus

Authors: Jan Brabender, Daniel Vallböhmer, Peter Grimminger, Andreas C. Hoffmann, Frederike Ling, Georg Lurje, Elfriede Bollschweiler, Paul M. Schneider, Arnulf H. Hölscher, Ralf Metzger

Published in: Journal of Gastrointestinal Surgery | Issue 11/2008

Login to get access

Abstract

Objective

The aim of this study was to determine the gene is spelled excision repair cross-complementing gene 1 (ERCC1) RNA-expression in peripheral blood as a non-invasive molecular predictor of response to neoadjuvant radio-chemotherapy in patients with locally advanced cancer of the esophagus.

Background

Only patients with locally advanced cancer of the esophagus with a major histopathological response to neoadjuvant radio-chemotherapy benefit from this treatment. No non-invasive molecular marker exists that can reliably predict response to neoadjuvant therapy in this disease. To improve the treatment of patients with cancer of the esophagus, molecular predictors of response are desperately needed.

Methods

Blood samples were drawn from 29 patients with esophageal cancer prior to neoadjuvant radio-chemotherapy. After extraction of cellular tumor-RNA from blood samples, quantitative expression analysis of ERCC1 was done by real-time reverse transcription polymerase chain reaction.

Results

Nineteen (65.5%) patients showed a minor and ten (34.5%) a major histopathological response to neoadjuvant therapy. ERCC1 expression in blood of patients was detectable in 82.8%. The median ERCC1 expression was 0.62 (minimum 0.00, maximum 2.48) in minor responders and 0.24 (minimum 0.00, maximum 0.45) in major responders (p = 0.004). No significant associations were detectable between ERCC1 levels and patients’ clinical variables. Relative ERCC1 levels above 0.452 were not associated with major histopathological response (sensitivity, 68.4; specificity, 100%), and 13 of 19 patients with minor response could be unequivocally identified.

Conclusion

Minor responders to the applied therapy show a significant higher ERCC1 expression level in their blood compared to major responders. ERCC1 appears to be a highly specific non-invasive predictor of response to neoadjuvant therapy in esophageal cancer.
Literature
3.
go back to reference Urba SG, et al. Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma. J Clin Oncol 2001;19(2):305–313.PubMed Urba SG, et al. Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma. J Clin Oncol 2001;19(2):305–313.PubMed
6.
go back to reference Higashi H, et al. Down-regulation of Gadd45 expression is associated with tumor differentiation in non-small cell lung cancer. Anticancer Res 2006;26(3A):2143–2147.PubMed Higashi H, et al. Down-regulation of Gadd45 expression is associated with tumor differentiation in non-small cell lung cancer. Anticancer Res 2006;26(3A):2143–2147.PubMed
7.
go back to reference Ling FC, et al. HIF-1alpha mRNA is not associated with histopathological regression following neoadjuvant chemoradiation in esophageal cancer. Anticancer Res 2006;26(6B):4505–4509.PubMed Ling FC, et al. HIF-1alpha mRNA is not associated with histopathological regression following neoadjuvant chemoradiation in esophageal cancer. Anticancer Res 2006;26(6B):4505–4509.PubMed
9.
go back to reference Warnecke-Eberz U, et al. High specificity of quantitative excision repair cross-complementing 1 messenger RNA expression for prediction of minor histopathological response to neoadjuvant radiochemotherapy in esophageal cancer. Clin Cancer Res 2004;10(11):3794–3799. doi:10.1158/1078-0432.CCR-03-0079.PubMedCrossRef Warnecke-Eberz U, et al. High specificity of quantitative excision repair cross-complementing 1 messenger RNA expression for prediction of minor histopathological response to neoadjuvant radiochemotherapy in esophageal cancer. Clin Cancer Res 2004;10(11):3794–3799. doi:10.​1158/​1078-0432.​CCR-03-0079.PubMedCrossRef
10.
go back to reference Warnecke-Eberz U, et al. Overexpression of survivin mRNA is associated with a favorable prognosis following neoadjuvant radiochemotherapy in esophageal cancer. Oncol Rep 2005;13(6):1241–1246.PubMed Warnecke-Eberz U, et al. Overexpression of survivin mRNA is associated with a favorable prognosis following neoadjuvant radiochemotherapy in esophageal cancer. Oncol Rep 2005;13(6):1241–1246.PubMed
11.
go back to reference Miyazono F, et al. Quantitative c-erbB-2 but not c-erbB-1 mRNA expression is a promising marker to predict minor histopathologic response to neoadjuvant radiochemotherapy in oesophageal cancer. Br J Cancer 2004;91(4):666–672.PubMed Miyazono F, et al. Quantitative c-erbB-2 but not c-erbB-1 mRNA expression is a promising marker to predict minor histopathologic response to neoadjuvant radiochemotherapy in oesophageal cancer. Br J Cancer 2004;91(4):666–672.PubMed
13.
go back to reference Hoffmann AC, et al. Survivin mRNA in peripheral blood is frequently detected and significantly decreased following resection of gastrointestinal cancers. J Surg Oncol 2007;95(1):51–54. doi:10.1002/jso.20630.PubMedCrossRef Hoffmann AC, et al. Survivin mRNA in peripheral blood is frequently detected and significantly decreased following resection of gastrointestinal cancers. J Surg Oncol 2007;95(1):51–54. doi:10.​1002/​jso.​20630.PubMedCrossRef
14.
go back to reference Shirota Y, et al. ERCC1 and thymidylate synthase mRNA levels predict survival for colorectal cancer patients receiving combination oxaliplatin and fluorouracil chemotherapy. J Clin Oncol 2001;19(23):4298–4304.PubMed Shirota Y, et al. ERCC1 and thymidylate synthase mRNA levels predict survival for colorectal cancer patients receiving combination oxaliplatin and fluorouracil chemotherapy. J Clin Oncol 2001;19(23):4298–4304.PubMed
15.
go back to reference Metzger R, et al. ERCC1 mRNA levels complement thymidylate synthase mRNA levels in predicting response and survival for gastric cancer patients receiving combination cisplatin and fluorouracil chemotherapy. J Clin Oncol 1998;16(1):309–316.PubMed Metzger R, et al. ERCC1 mRNA levels complement thymidylate synthase mRNA levels in predicting response and survival for gastric cancer patients receiving combination cisplatin and fluorouracil chemotherapy. J Clin Oncol 1998;16(1):309–316.PubMed
16.
go back to reference Lord RV, et al. Low ERCC1 expression correlates with prolonged survival after cisplatin plus gemcitabine chemotherapy in non-small cell lung cancer. Clin Cancer Res 2002;8(7):2286–2291.PubMed Lord RV, et al. Low ERCC1 expression correlates with prolonged survival after cisplatin plus gemcitabine chemotherapy in non-small cell lung cancer. Clin Cancer Res 2002;8(7):2286–2291.PubMed
17.
go back to reference Schroder W, et al. Frequency of nodal metastases to the upper mediastinum in Barrett’s cancer. Ann Surg Oncol 2002;9(8):807–811.PubMed Schroder W, et al. Frequency of nodal metastases to the upper mediastinum in Barrett’s cancer. Ann Surg Oncol 2002;9(8):807–811.PubMed
20.
go back to reference Metz CE, Goodenough DJ, Rossmann K. Evaluation of receiver operating characteristic curve data in terms of information theory, with applications in radiography. Radiology 1973;109(2):297–303.PubMed Metz CE, Goodenough DJ, Rossmann K. Evaluation of receiver operating characteristic curve data in terms of information theory, with applications in radiography. Radiology 1973;109(2):297–303.PubMed
22.
go back to reference Usadel H, et al. Quantitative adenomatous polyposis coli promoter methylation analysis in tumor tissue, serum, and plasma DNA of patients with lung cancer. Cancer Res 2002;62(2):371–375.PubMed Usadel H, et al. Quantitative adenomatous polyposis coli promoter methylation analysis in tumor tissue, serum, and plasma DNA of patients with lung cancer. Cancer Res 2002;62(2):371–375.PubMed
Metadata
Title
ERCC1 RNA Expression in Peripheral Blood Predicts Minor Histopathological Response to Neoadjuvant Radio-chemotherapy in Patients with Locally Advanced Cancer of the Esophagus
Authors
Jan Brabender
Daniel Vallböhmer
Peter Grimminger
Andreas C. Hoffmann
Frederike Ling
Georg Lurje
Elfriede Bollschweiler
Paul M. Schneider
Arnulf H. Hölscher
Ralf Metzger
Publication date
01-11-2008
Publisher
Springer-Verlag
Published in
Journal of Gastrointestinal Surgery / Issue 11/2008
Print ISSN: 1091-255X
Electronic ISSN: 1873-4626
DOI
https://doi.org/10.1007/s11605-008-0668-7

Other articles of this Issue 11/2008

Journal of Gastrointestinal Surgery 11/2008 Go to the issue