High-throughput tissue microarray analysis used to evaluate biology and prognostic significance of the E-cadherin pathway in non-small-cell lung cancer

Roy M. Bremnes, R. Veve, E. Gabrielson, F. R. Hirsch, A. Baron, L. Bemis, R. M. Gemmill, H. A. Drabkin, W. A. Franklin

Research output: Contribution to journalArticle

244 Citations (Scopus)

Abstract

Purpose: E-cadherin (E-cad) and its associated intracellular molecules, catenins, are critical for intercellular epithelial adhesion and are often expressed in nonsmall-cell lung carcinomas (NSCLCs). We constructed tissue microarrays (TMAs) to investigate the expression of cadherins and catenins and their prognostic significance in NSCLC. Patients and Methods: Tumor tissue samples from 193 patients with stages I to III NSCLC were obtained from the University of Colorado Cancer Center and Johns Hopkins Medical Institutions. Viable tumor was sampled in triplicate for the TMAs, and slides were stained by immunohistochemistry with antibodies against E-cad, N-cadherin, alpha (α)-, beta (β)-, and gamma (γ)-catenin, p 120, p27, and adenomatous polyposis coli (APC) gene product. Clinical data were collected by the tumor registries. Patients were followed for a median period of 51 months (range, 18 to 100 months). Results: Absent or severely reduced membranous expression for E-cad, α-, β-, and γ-catenin, and p120 were observed in 10%, 17%, 8%, 31 %, and 61% of the cases, respectively. Tumor cell dedifferentiation correlated with reduced expression for E-cad, β-catenin, γ-catenin, and p120 in squamous cell carcinomas but not in adenocarcinomas. There was an inverse correlation between nodal metastasis and expression of E-cad and γ-catenin. Besides the traditional clinical prognostic variables, E-cad and α-, β-, and γ-catenin expression were of positive prognostic value in univariate survival analyses. In multivariate analysis, E-cad expression was the only independent prognostic factor for survival in addition to age, node status, tumor status, and pathologic surgical margins. Conclusion: Reduced expression of E-cad and catenins is associated with tumor cell dedifferentiation, local invasion, regional metastasis, and reduced survival in NSCLC. E-cad is an independent prognostic factor for NSCLC survival.

Original languageEnglish (US)
Pages (from-to)2417-2428
Number of pages12
JournalJournal of Clinical Oncology
Volume20
Issue number10
DOIs
StatePublished - May 15 2002

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Tissue Array Analysis
Catenins
Cadherins
Non-Small Cell Lung Carcinoma
Carcinoma
Lung
Cell Dedifferentiation
Neoplasms
Survival
gamma Catenin
APC Genes
Neoplasm Metastasis
beta Catenin
Survival Analysis
Registries
Squamous Cell Carcinoma
Adenocarcinoma
Multivariate Analysis
Immunohistochemistry
Antibodies

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High-throughput tissue microarray analysis used to evaluate biology and prognostic significance of the E-cadherin pathway in non-small-cell lung cancer. / Bremnes, Roy M.; Veve, R.; Gabrielson, E.; Hirsch, F. R.; Baron, A.; Bemis, L.; Gemmill, R. M.; Drabkin, H. A.; Franklin, W. A.

In: Journal of Clinical Oncology, Vol. 20, No. 10, 15.05.2002, p. 2417-2428.

Research output: Contribution to journalArticle

Bremnes, Roy M. ; Veve, R. ; Gabrielson, E. ; Hirsch, F. R. ; Baron, A. ; Bemis, L. ; Gemmill, R. M. ; Drabkin, H. A. ; Franklin, W. A. / High-throughput tissue microarray analysis used to evaluate biology and prognostic significance of the E-cadherin pathway in non-small-cell lung cancer. In: Journal of Clinical Oncology. 2002 ; Vol. 20, No. 10. pp. 2417-2428.
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abstract = "Purpose: E-cadherin (E-cad) and its associated intracellular molecules, catenins, are critical for intercellular epithelial adhesion and are often expressed in nonsmall-cell lung carcinomas (NSCLCs). We constructed tissue microarrays (TMAs) to investigate the expression of cadherins and catenins and their prognostic significance in NSCLC. Patients and Methods: Tumor tissue samples from 193 patients with stages I to III NSCLC were obtained from the University of Colorado Cancer Center and Johns Hopkins Medical Institutions. Viable tumor was sampled in triplicate for the TMAs, and slides were stained by immunohistochemistry with antibodies against E-cad, N-cadherin, alpha (α)-, beta (β)-, and gamma (γ)-catenin, p 120, p27, and adenomatous polyposis coli (APC) gene product. Clinical data were collected by the tumor registries. Patients were followed for a median period of 51 months (range, 18 to 100 months). Results: Absent or severely reduced membranous expression for E-cad, α-, β-, and γ-catenin, and p120 were observed in 10{\%}, 17{\%}, 8{\%}, 31 {\%}, and 61{\%} of the cases, respectively. Tumor cell dedifferentiation correlated with reduced expression for E-cad, β-catenin, γ-catenin, and p120 in squamous cell carcinomas but not in adenocarcinomas. There was an inverse correlation between nodal metastasis and expression of E-cad and γ-catenin. Besides the traditional clinical prognostic variables, E-cad and α-, β-, and γ-catenin expression were of positive prognostic value in univariate survival analyses. In multivariate analysis, E-cad expression was the only independent prognostic factor for survival in addition to age, node status, tumor status, and pathologic surgical margins. Conclusion: Reduced expression of E-cad and catenins is associated with tumor cell dedifferentiation, local invasion, regional metastasis, and reduced survival in NSCLC. E-cad is an independent prognostic factor for NSCLC survival.",
author = "Bremnes, {Roy M.} and R. Veve and E. Gabrielson and Hirsch, {F. R.} and A. Baron and L. Bemis and Gemmill, {R. M.} and Drabkin, {H. A.} and Franklin, {W. A.}",
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T1 - High-throughput tissue microarray analysis used to evaluate biology and prognostic significance of the E-cadherin pathway in non-small-cell lung cancer

AU - Bremnes, Roy M.

AU - Veve, R.

AU - Gabrielson, E.

AU - Hirsch, F. R.

AU - Baron, A.

AU - Bemis, L.

AU - Gemmill, R. M.

AU - Drabkin, H. A.

AU - Franklin, W. A.

PY - 2002/5/15

Y1 - 2002/5/15

N2 - Purpose: E-cadherin (E-cad) and its associated intracellular molecules, catenins, are critical for intercellular epithelial adhesion and are often expressed in nonsmall-cell lung carcinomas (NSCLCs). We constructed tissue microarrays (TMAs) to investigate the expression of cadherins and catenins and their prognostic significance in NSCLC. Patients and Methods: Tumor tissue samples from 193 patients with stages I to III NSCLC were obtained from the University of Colorado Cancer Center and Johns Hopkins Medical Institutions. Viable tumor was sampled in triplicate for the TMAs, and slides were stained by immunohistochemistry with antibodies against E-cad, N-cadherin, alpha (α)-, beta (β)-, and gamma (γ)-catenin, p 120, p27, and adenomatous polyposis coli (APC) gene product. Clinical data were collected by the tumor registries. Patients were followed for a median period of 51 months (range, 18 to 100 months). Results: Absent or severely reduced membranous expression for E-cad, α-, β-, and γ-catenin, and p120 were observed in 10%, 17%, 8%, 31 %, and 61% of the cases, respectively. Tumor cell dedifferentiation correlated with reduced expression for E-cad, β-catenin, γ-catenin, and p120 in squamous cell carcinomas but not in adenocarcinomas. There was an inverse correlation between nodal metastasis and expression of E-cad and γ-catenin. Besides the traditional clinical prognostic variables, E-cad and α-, β-, and γ-catenin expression were of positive prognostic value in univariate survival analyses. In multivariate analysis, E-cad expression was the only independent prognostic factor for survival in addition to age, node status, tumor status, and pathologic surgical margins. Conclusion: Reduced expression of E-cad and catenins is associated with tumor cell dedifferentiation, local invasion, regional metastasis, and reduced survival in NSCLC. E-cad is an independent prognostic factor for NSCLC survival.

AB - Purpose: E-cadherin (E-cad) and its associated intracellular molecules, catenins, are critical for intercellular epithelial adhesion and are often expressed in nonsmall-cell lung carcinomas (NSCLCs). We constructed tissue microarrays (TMAs) to investigate the expression of cadherins and catenins and their prognostic significance in NSCLC. Patients and Methods: Tumor tissue samples from 193 patients with stages I to III NSCLC were obtained from the University of Colorado Cancer Center and Johns Hopkins Medical Institutions. Viable tumor was sampled in triplicate for the TMAs, and slides were stained by immunohistochemistry with antibodies against E-cad, N-cadherin, alpha (α)-, beta (β)-, and gamma (γ)-catenin, p 120, p27, and adenomatous polyposis coli (APC) gene product. Clinical data were collected by the tumor registries. Patients were followed for a median period of 51 months (range, 18 to 100 months). Results: Absent or severely reduced membranous expression for E-cad, α-, β-, and γ-catenin, and p120 were observed in 10%, 17%, 8%, 31 %, and 61% of the cases, respectively. Tumor cell dedifferentiation correlated with reduced expression for E-cad, β-catenin, γ-catenin, and p120 in squamous cell carcinomas but not in adenocarcinomas. There was an inverse correlation between nodal metastasis and expression of E-cad and γ-catenin. Besides the traditional clinical prognostic variables, E-cad and α-, β-, and γ-catenin expression were of positive prognostic value in univariate survival analyses. In multivariate analysis, E-cad expression was the only independent prognostic factor for survival in addition to age, node status, tumor status, and pathologic surgical margins. Conclusion: Reduced expression of E-cad and catenins is associated with tumor cell dedifferentiation, local invasion, regional metastasis, and reduced survival in NSCLC. E-cad is an independent prognostic factor for NSCLC survival.

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