Publication

Tubulin, BRCA1, ERCC1, Abraxas, RAP80 mRNA expression, p53/p21 immunohistochemistry and clinical outcome in patients with advanced non small-cell lung cancer receiving first-line platinum-gemcitabine chemotherapy

Journal Paper/Review - Apr 29, 2011

Units
PubMed
Doi

Citation
Jörger M, deJong D, Burylo A, Burgers J, Baas P, Huitema A, Beijnen J, Schellens J. Tubulin, BRCA1, ERCC1, Abraxas, RAP80 mRNA expression, p53/p21 immunohistochemistry and clinical outcome in patients with advanced non small-cell lung cancer receiving first-line platinum-gemcitabine chemotherapy. Lung Cancer 2011; 74:310-7.
Type
Journal Paper/Review (English)
Journal
Lung Cancer 2011; 74
Publication Date
Apr 29, 2011
Issn Electronic
1872-8332
Pages
310-7
Brief description/objective

BACKGROUND
The aim of this study was to assess the predictive value of tumor expression of nine genes on clinical outcome in patients with advanced NSCLC receiving platinum-gemcitabine chemotherapy.

METHODS
Quantitative PCR or immunohistochemistry were used to analyze the expression of β-tubuline IIA (TUBB2A), β-tubuline III (TUBB3), BRCA1, ERCC1, Abraxas (ABRX) and RAP80 in mRNA isolated from paraffin-embedded tumor biopsies of 45 NSCLC patients treated as part of a larger observational trial. All patients received first-line platinum-gemcitabine chemotherapy for stage IIIB or IV NSCLC.

RESULTS
Median progression-free survival (PFS) was 7 months, overall survival (OS) 12 months. A partial treatment response was found in 14 patients (33%). Patients with low ERCC1 or ABRX expression had a significantly better response to chemotherapy (R=-0.45, p<0.01 for ERCC1; R=-0.40, p=0.016 for ABRX). A significant correlation was found between the individual time for PFS and the expression of both ERCC1 (R=-0.36, p=0.015) and ABRX (R=-0.46, p=0.001). Patients with low ERCC1 expression had a longer OS as compared to patients with high ERCC1 expression (HR=0.26, log-rank p=0.02).

CONCLUSIONS
The study confirms tumor expression of ERCC1 as a predictor for clinical outcome in patients with advanced NSCLC receiving platinum-based chemotherapy, and found ABRX expression to be similarly predictive of clinical outcome. Prospective validation is warranted and - if confirmed - non platinum-containing chemotherapy should be explored as the preferred treatment in patients with high ERCC1 or ABRX expression and no activating mutations of EGFR.