Immunohistochemical analysis of C/EBPα in non-small cell lung cancer reveals frequent down-regulation in stage II and IIIA tumors

A correlative study of E3590

Daniel B. Costa, Sigui Li, Olivier Kocher, Richard H. Feins, Steven M. Keller, Joan H. Schiller, David H. Johnson, Daniel G. Tenen, Balazs Halmos

Research output: Contribution to journalArticle

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Abstract

Purpose: We sought to determine the association of C/EBPα expression status with clinical, pathologic and molecular characteristics, as well as outcomes, in non-small-cell lung cancer (NSCLC). This is the first comprehensive study of this transcription factor in patients with NSCLC. Patients and methods: Our cohort originated from ECOG 3590 (randomized trial of postoperative adjuvant therapy with thoracic radiation or cisplatin and etoposide plus thoracic radiation in patients with completely resected stages II and IIIA NSCLC; and its laboratory correlate, ECOG 4592). One hundred and sixty four tumor samples contained sufficient material for immunohistochemical (IHC) analysis. C/EBPα tumor staining was compared to that of basal bronchial cells (3+). 0 or 1+ (weak) suggested lack of, while 2 or 3+ (strong) suggested C/EBPα expression. Results: Ninety tumors (55%) had 0 or 1+ C/EBPα staining, and the remaining 74 (45%) 2 or 3+. Patients with squamous cell carcinomas had a higher percentage of weak C/EBPα IHC staining compared to other histologies (p = 0.048) and there was a trend for loss of C/EBPα in poorly differentiated compared to well differentiated tumors (p = 0.07). There was no association between C/EBPα IHC and mutations in p53 or K-ras. The median disease-free survival for patients with weak and strong C/EBPα IHC expression was 29.6 and 30.6 months, respectively (p = 0.94). The median overall survival between the weak and strong groups was 43.5 and 38.5 months, respectively (p = 0.83). Conclusions: Loss of expression of C/EBPα is seen in over half of stage II and IIIA NSCLC, specifically in squamous cell carcinomas and poorly differentiated tumors. Since down-regulation of C/EBPα is a common event in NSCLC, further elucidation of the involvement of C/EBPα in the pathogenesis and progression of lung cancer may identify novel therapeutic targets.

Original languageEnglish (US)
Pages (from-to)97-103
Number of pages7
JournalLung Cancer
Volume56
Issue number1
DOIs
StatePublished - Apr 2007

Fingerprint

Non-Small Cell Lung Carcinoma
Down-Regulation
Neoplasms
Staining and Labeling
Squamous Cell Carcinoma
Thorax
Radiation
Etoposide
Cisplatin
Disease-Free Survival
Lung Neoplasms
Histology
Transcription Factors
Mutation
Survival
Therapeutics

Keywords

  • C/EBPα
  • Immunohistochemistry
  • Lung cancer
  • Non-small cell lung cancer
  • Squamous cell carcinoma
  • Survival
  • Transcription factor

ASJC Scopus subject areas

  • Oncology

Cite this

Immunohistochemical analysis of C/EBPα in non-small cell lung cancer reveals frequent down-regulation in stage II and IIIA tumors : A correlative study of E3590. / Costa, Daniel B.; Li, Sigui; Kocher, Olivier; Feins, Richard H.; Keller, Steven M.; Schiller, Joan H.; Johnson, David H.; Tenen, Daniel G.; Halmos, Balazs.

In: Lung Cancer, Vol. 56, No. 1, 04.2007, p. 97-103.

Research output: Contribution to journalArticle

Costa, Daniel B. ; Li, Sigui ; Kocher, Olivier ; Feins, Richard H. ; Keller, Steven M. ; Schiller, Joan H. ; Johnson, David H. ; Tenen, Daniel G. ; Halmos, Balazs. / Immunohistochemical analysis of C/EBPα in non-small cell lung cancer reveals frequent down-regulation in stage II and IIIA tumors : A correlative study of E3590. In: Lung Cancer. 2007 ; Vol. 56, No. 1. pp. 97-103.
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abstract = "Purpose: We sought to determine the association of C/EBPα expression status with clinical, pathologic and molecular characteristics, as well as outcomes, in non-small-cell lung cancer (NSCLC). This is the first comprehensive study of this transcription factor in patients with NSCLC. Patients and methods: Our cohort originated from ECOG 3590 (randomized trial of postoperative adjuvant therapy with thoracic radiation or cisplatin and etoposide plus thoracic radiation in patients with completely resected stages II and IIIA NSCLC; and its laboratory correlate, ECOG 4592). One hundred and sixty four tumor samples contained sufficient material for immunohistochemical (IHC) analysis. C/EBPα tumor staining was compared to that of basal bronchial cells (3+). 0 or 1+ (weak) suggested lack of, while 2 or 3+ (strong) suggested C/EBPα expression. Results: Ninety tumors (55{\%}) had 0 or 1+ C/EBPα staining, and the remaining 74 (45{\%}) 2 or 3+. Patients with squamous cell carcinomas had a higher percentage of weak C/EBPα IHC staining compared to other histologies (p = 0.048) and there was a trend for loss of C/EBPα in poorly differentiated compared to well differentiated tumors (p = 0.07). There was no association between C/EBPα IHC and mutations in p53 or K-ras. The median disease-free survival for patients with weak and strong C/EBPα IHC expression was 29.6 and 30.6 months, respectively (p = 0.94). The median overall survival between the weak and strong groups was 43.5 and 38.5 months, respectively (p = 0.83). Conclusions: Loss of expression of C/EBPα is seen in over half of stage II and IIIA NSCLC, specifically in squamous cell carcinomas and poorly differentiated tumors. Since down-regulation of C/EBPα is a common event in NSCLC, further elucidation of the involvement of C/EBPα in the pathogenesis and progression of lung cancer may identify novel therapeutic targets.",
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author = "Costa, {Daniel B.} and Sigui Li and Olivier Kocher and Feins, {Richard H.} and Keller, {Steven M.} and Schiller, {Joan H.} and Johnson, {David H.} and Tenen, {Daniel G.} and Balazs Halmos",
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T2 - A correlative study of E3590

AU - Costa, Daniel B.

AU - Li, Sigui

AU - Kocher, Olivier

AU - Feins, Richard H.

AU - Keller, Steven M.

AU - Schiller, Joan H.

AU - Johnson, David H.

AU - Tenen, Daniel G.

AU - Halmos, Balazs

PY - 2007/4

Y1 - 2007/4

N2 - Purpose: We sought to determine the association of C/EBPα expression status with clinical, pathologic and molecular characteristics, as well as outcomes, in non-small-cell lung cancer (NSCLC). This is the first comprehensive study of this transcription factor in patients with NSCLC. Patients and methods: Our cohort originated from ECOG 3590 (randomized trial of postoperative adjuvant therapy with thoracic radiation or cisplatin and etoposide plus thoracic radiation in patients with completely resected stages II and IIIA NSCLC; and its laboratory correlate, ECOG 4592). One hundred and sixty four tumor samples contained sufficient material for immunohistochemical (IHC) analysis. C/EBPα tumor staining was compared to that of basal bronchial cells (3+). 0 or 1+ (weak) suggested lack of, while 2 or 3+ (strong) suggested C/EBPα expression. Results: Ninety tumors (55%) had 0 or 1+ C/EBPα staining, and the remaining 74 (45%) 2 or 3+. Patients with squamous cell carcinomas had a higher percentage of weak C/EBPα IHC staining compared to other histologies (p = 0.048) and there was a trend for loss of C/EBPα in poorly differentiated compared to well differentiated tumors (p = 0.07). There was no association between C/EBPα IHC and mutations in p53 or K-ras. The median disease-free survival for patients with weak and strong C/EBPα IHC expression was 29.6 and 30.6 months, respectively (p = 0.94). The median overall survival between the weak and strong groups was 43.5 and 38.5 months, respectively (p = 0.83). Conclusions: Loss of expression of C/EBPα is seen in over half of stage II and IIIA NSCLC, specifically in squamous cell carcinomas and poorly differentiated tumors. Since down-regulation of C/EBPα is a common event in NSCLC, further elucidation of the involvement of C/EBPα in the pathogenesis and progression of lung cancer may identify novel therapeutic targets.

AB - Purpose: We sought to determine the association of C/EBPα expression status with clinical, pathologic and molecular characteristics, as well as outcomes, in non-small-cell lung cancer (NSCLC). This is the first comprehensive study of this transcription factor in patients with NSCLC. Patients and methods: Our cohort originated from ECOG 3590 (randomized trial of postoperative adjuvant therapy with thoracic radiation or cisplatin and etoposide plus thoracic radiation in patients with completely resected stages II and IIIA NSCLC; and its laboratory correlate, ECOG 4592). One hundred and sixty four tumor samples contained sufficient material for immunohistochemical (IHC) analysis. C/EBPα tumor staining was compared to that of basal bronchial cells (3+). 0 or 1+ (weak) suggested lack of, while 2 or 3+ (strong) suggested C/EBPα expression. Results: Ninety tumors (55%) had 0 or 1+ C/EBPα staining, and the remaining 74 (45%) 2 or 3+. Patients with squamous cell carcinomas had a higher percentage of weak C/EBPα IHC staining compared to other histologies (p = 0.048) and there was a trend for loss of C/EBPα in poorly differentiated compared to well differentiated tumors (p = 0.07). There was no association between C/EBPα IHC and mutations in p53 or K-ras. The median disease-free survival for patients with weak and strong C/EBPα IHC expression was 29.6 and 30.6 months, respectively (p = 0.94). The median overall survival between the weak and strong groups was 43.5 and 38.5 months, respectively (p = 0.83). Conclusions: Loss of expression of C/EBPα is seen in over half of stage II and IIIA NSCLC, specifically in squamous cell carcinomas and poorly differentiated tumors. Since down-regulation of C/EBPα is a common event in NSCLC, further elucidation of the involvement of C/EBPα in the pathogenesis and progression of lung cancer may identify novel therapeutic targets.

KW - C/EBPα

KW - Immunohistochemistry

KW - Lung cancer

KW - Non-small cell lung cancer

KW - Squamous cell carcinoma

KW - Survival

KW - Transcription factor

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