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Molecular Marker Expression Is Highly Heterogeneous in Esophageal Adenocarcinoma and Does Not Predict a Response to Neoadjuvant Therapy

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Journal of Gastrointestinal Surgery Aims and scope

Abstract

A reliable method to identify pathologic complete responders (pCR) or non-responders (NR) to neoadjuvant chemoradiation therapy (NAT) would dramatically improve therapy for esophageal cancer. The purpose of this study is to investigate if a distinct profile of prognostic molecular markers can predict pCR after neoadjuvant therapy. Expression of p53, Her-2/neu, Cox-2, Beta-catenin, E-cadherin, MMP-1, NFkB, and TGF-B was measured by immunohistochemistry in pre-treatment biopsy tissue and graded by an experienced pathologist. A pCR was defined as no evidence of malignancy on final pathology. Molecular profiles comparing responders to non-responders were analyzed using classification and regression tree analysis to investigate response to NAT and overall survival. Nineteen patients were pCRs and 34 were NRs. pCRs were more likely to be alive at follow-up than NRs (p < 0.01). Thirty-seven distinct profiles were identified. Expression of molecular markers was highly heterogeneous between patients and did not correlate with a response to NAT, survival (p = 0.47) or clinical stage (p = 0.39) when evaluated either as individual markers or in combination with other expression patterns. NAT dramatically impacts survival through a mechanism independent of known molecular markers of esophageal cancer, which are expressed in a highly heterogeneous fashion and do not predict response to NAT or survival.

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Acknowledgments

The authors wish to thank Cara Poage, Kelli Forquer, and Linh Matsumura for their expertise in performing the immunohistochemistry for this study.

Grant Support

Michael J Newton Esophageal Cancer Research Foundation (Bronson) and NIH T32 GM082770 (Dolan).

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Authors and Affiliations

  1. Department of Surgery, Division of Gastrointestinal and General Surgery, and The Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA

    Nathan W. Bronson, Brian S. Diggs, Brett C. Sheppard, John G. Hunter & James P. Dolan

  2. Department of Medicine, Division of Gastroenterology, Oregon Health and Science University, Portland, OR, USA

    Gene Bakis

  3. Department of Pathology, Oregon Health and Science University, Portland, OR, USA

    Kenneth M. Gatter

Authors
  1. Nathan W. Bronson
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  2. Brian S. Diggs
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  3. Gene Bakis
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  4. Kenneth M. Gatter
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  5. Brett C. Sheppard
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  6. John G. Hunter
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  7. James P. Dolan
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Corresponding author

Correspondence to James P. Dolan.

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Bronson, N.W., Diggs, B.S., Bakis, G. et al. Molecular Marker Expression Is Highly Heterogeneous in Esophageal Adenocarcinoma and Does Not Predict a Response to Neoadjuvant Therapy. J Gastrointest Surg 19, 2105–2110 (2015). https://doi.org/10.1007/s11605-015-2944-7

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  • DOI: https://doi.org/10.1007/s11605-015-2944-7

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