The prognostic significance of ERCC1, BRCA1, XRCC1, and betaIII-tubulin expression in patients with non-small cell lung cancer treated by platinum- and taxane-based neoadjuvant chemotherapy and surgical resection.

Abstract

OBJECTIVES:

The DNA repair pathway and isotype composition of beta-tubulin are known to be associated with resistance to platinum- and taxane-based chemotherapy, respectively. The aim of this study was to identify the clinical significance of excision repair cross-complementation 1 (ERCC1), breast cancer susceptibility gene 1 (BRCA1), X-ray repair cross-complementation 1 (XRCC1) and betaIII-tubulin on the chemotherapy response and overall survival in patients with non-small cell lung cancer (NSCLC) who received neoadjuvant chemotherapy.

METHODS:

Protein expression profiles were evaluated by immunohistochemistry on surgical specimens of 82 NSCLC patients who underwent platinum- and taxane-based neoadjuvant chemotherapy. The expression levels of proteins were measured semi-quantitatively and the correlation with tumor responses, pathologic cell death rate and survival were evaluated.

RESULTS:

There were 73 (89.0%) clinical stage III patients. Lobectomy, bilobectomy, and pneumonectomy were performed in 54 (65.0%), 11 (13.4%), and 17 (20.7%) patients, respectively. There was no correlation between clinical response and protein expression. The expression levels of ERCC1, BRCA1, and XRCC1 increased proportionally to the cell death rate (p<0.05); however, betaIII-tubulin expression did not correlate with cell viability. Multivariate analysis demonstrated that early pathologic stage, adjuvant chemotherapy, high ERCC1 and low betaIII-tubulin expression were good prognostic factors for overall survival (p<0.05).

CONCLUSIONS:

The inverse correlation between DNA repair proteins and cell viability suggests that these protein expression levels can be markers for chemotherapy responsiveness. However, only ERCC1 and betaIII-tubulin were prognostic factors after platinum- and taxane-based neoadjuvant chemotherapy following surgical resection.

• Authors: Chang Hyun Kang, Bo Gun Jang, Dong-Wan Kim, Doo Hyun Chung, Young Tae Kim, Sanghoon Jheon, Sook-Whan Sung, Joo Hyun Kim
• Journal: Lung cancer (Amsterdam, Netherlands) (Lung Cancer) Vol. 68 Issue 3 Pg. 478-83 (Jun 2010) ISSN: 1872-8332 [Electronic] Ireland
• PMID: 19683826 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• BRCA1 Protein
• Bridged-Ring Compounds
• DNA-Binding Proteins
• Platinum Compounds
• TUBB3 protein, human
• Taxoids
• Tubulin
• X-ray Repair Cross Complementing Protein 1
• XRCC1 protein, human
• taxane
• ERCC1 protein, human
• Endonucleases

Topics

• Adult
• Aged
• BRCA1 Protein (metabolism)
• Bridged-Ring Compounds (administration & dosage, adverse effects)
• Carcinoma, Non-Small-Cell Lung (diagnosis, metabolism, mortality, pathology, physiopathology, therapy)
• DNA-Binding Proteins (metabolism)
• Drug Resistance, Neoplasm
• Endonucleases (metabolism)
• Female
• Humans
• Immunohistochemistry
• Lung Neoplasms (diagnosis, metabolism, mortality, pathology, physiopathology, therapy)
• Male
• Middle Aged
• Neoadjuvant Therapy
• Neoplasm Staging
• Platinum Compounds (administration & dosage, adverse effects)
• Pneumonectomy
• Predictive Value of Tests
• Prognosis
• Survival Analysis
• Taxoids (administration & dosage, adverse effects)
• Tubulin (metabolism)
• X-ray Repair Cross Complementing Protein 1