Excision repair cross complementing-1 and topoisomerase IIalpha gene expression in small-cell lung cancer patients treated with platinum and etoposide: a retrospective study.

Abstract

HYPOTHESIS:

Aim of the study was to quantify ERCC1, RRM1, and TopoIIalpha mRNA expression profile as predictive factors for response and survival in SCLC patients treated with platinum/etoposide.

METHODS:

Total RNA was extracted from microdissected sections of 103 formalin-fixed, paraffin embedded biopsies. Relative quantification was performed by real-time polymerase chain reaction (PCR) using intron-spanning probes.

RESULTS:

Eighty-five samples (83%) were successfully amplified. Median overall survival (OS) was 9.9 months; 45 patients had limited disease (LD) (OS = 13.1) and 40 had extensive disease (ED) (OS = 7.1). Fifty-six (65%) patients had an objective response to treatment. A gene expression was detectable in all samples and a correlation between ERCC1 and RRM1 (Rs = 0.34, p = 0.0011) was found. According to response to treatment, it was found that lower TopoIIalpha expression was associated to a better response in LD patients (p = 0.025) and, more interestingly, those who had a complete response had lower TopoIIalpha than both partial and nonresponsive patients (p = 0.015). At univariate analysis LD patients with low ERCC1 had significantly longer survival (median survival 14.9 versus 9.9, p = 0.012), whereas RRM1 and TopoIIalpha levels showed no influence on outcome. At the multivariate analysis, ERCC1 was confirmed to be an independent prognostic factor for survival in LD patients. No significant role was found for ERCC1, RRM1 and TopoIIalpha in ED patients.

CONCLUSIONS:

ERCC1 and TopoIIalpha are candidate markers in predicting clinical outcome and response to treatment in LD SCLC patients and are worth of further investigation in a prospective study.

• Authors: Paolo Ceppi, Marina Longo, Marco Volante, Silvia Novello, Susanna Cappia, Elisa Bacillo, Giovanni Selvaggi, Silvia Saviozzi, Raffaele Calogero, Mauro Papotti, Giorgio V Scagliotti
• Journal: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer (J Thorac Oncol) Vol. 3 Issue 6 Pg. 583-9 (Jun 2008) ISSN: 1556-1380 [Electronic] United States
• PMID: 18520795 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Antigens, Neoplasm
• Antineoplastic Agents
• Biomarkers, Tumor
• DNA, Neoplasm
• DNA-Binding Proteins
• Isoenzymes
• Platinum Compounds
• Etoposide
• Carboplatin
• ERCC1 protein, human
• Endonucleases
• DNA Topoisomerases, Type II
• Cisplatin

Topics

• Adult
• Aged
• Aged, 80 and over
• Antigens, Neoplasm (biosynthesis, genetics)
• Antineoplastic Agents (therapeutic use)
• Biomarkers, Tumor
• Carboplatin (therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics, mortality)
• Cisplatin (therapeutic use)
• DNA Repair
• DNA Topoisomerases, Type II (biosynthesis, genetics)
• DNA, Neoplasm (genetics)
• DNA-Binding Proteins (biosynthesis, genetics)
• Endonucleases (biosynthesis, genetics)
• Etoposide (therapeutic use)
• Female
• Follow-Up Studies
• Gene Expression Regulation, Neoplastic
• Humans
• Isoenzymes
• Italy (epidemiology)
• Lung Neoplasms (drug therapy, genetics, mortality)
• Male
• Middle Aged
• Platinum Compounds (therapeutic use)
• Polymerase Chain Reaction
• Prognosis
• Retrospective Studies
• Severity of Illness Index
• Survival Rate