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

Nathan Bronson, Brian S. Diggs, Gennadiy Bakis, Ken Gatter, Brett Sheppard, John Hunter, James Dolan

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2105-2110
Number of pages6
JournalJournal of Gastrointestinal Surgery
Volume19
Issue number12
DOIs
StatePublished - Dec 1 2015

Fingerprint

Neoadjuvant Therapy
Adenocarcinoma
Survival
Cadherins
Esophageal Neoplasms
beta Catenin
Matrix Metalloproteinases
Immunohistochemistry
Regression Analysis
Pathology
Biopsy
Therapeutics
Neoplasms

Keywords

  • Esophageal cancer
  • Molecular marker
  • Neoadjuvant therapy
  • Oesophageal cancer
  • Tumor profile

ASJC Scopus subject areas

  • Surgery
  • Gastroenterology

Cite this

Molecular Marker Expression Is Highly Heterogeneous in Esophageal Adenocarcinoma and Does Not Predict a Response to Neoadjuvant Therapy. / Bronson, Nathan; Diggs, Brian S.; Bakis, Gennadiy; Gatter, Ken; Sheppard, Brett; Hunter, John; Dolan, James.

In: Journal of Gastrointestinal Surgery, Vol. 19, No. 12, 01.12.2015, p. 2105-2110.

Research output: Contribution to journalArticle

@article{9c620922c2df4a188db3444cf8152341,
title = "Molecular Marker Expression Is Highly Heterogeneous in Esophageal Adenocarcinoma and Does Not Predict a Response to Neoadjuvant Therapy",
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.",
keywords = "Esophageal cancer, Molecular marker, Neoadjuvant therapy, Oesophageal cancer, Tumor profile",
author = "Nathan Bronson and Diggs, {Brian S.} and Gennadiy Bakis and Ken Gatter and Brett Sheppard and John Hunter and James Dolan",
year = "2015",
month = "12",
day = "1",
doi = "10.1007/s11605-015-2944-7",
language = "English (US)",
volume = "19",
pages = "2105--2110",
journal = "Journal of Gastrointestinal Surgery",
issn = "1091-255X",
publisher = "Springer New York",
number = "12",

}

TY - JOUR

T1 - Molecular Marker Expression Is Highly Heterogeneous in Esophageal Adenocarcinoma and Does Not Predict a Response to Neoadjuvant Therapy

AU - Bronson, Nathan

AU - Diggs, Brian S.

AU - Bakis, Gennadiy

AU - Gatter, Ken

AU - Sheppard, Brett

AU - Hunter, John

AU - Dolan, James

PY - 2015/12/1

Y1 - 2015/12/1

N2 - 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.

AB - 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.

KW - Esophageal cancer

KW - Molecular marker

KW - Neoadjuvant therapy

KW - Oesophageal cancer

KW - Tumor profile

UR - http://www.scopus.com/inward/record.url?scp=84947027047&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84947027047&partnerID=8YFLogxK

U2 - 10.1007/s11605-015-2944-7

DO - 10.1007/s11605-015-2944-7

M3 - Article

VL - 19

SP - 2105

EP - 2110

JO - Journal of Gastrointestinal Surgery

JF - Journal of Gastrointestinal Surgery

SN - 1091-255X

IS - 12

ER -