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

Autor: Giorgio V. Scagliotti, Elisa Bacillo, Mauro Papotti, Giovanni Selvaggi, Susanna Cappia, Silvia Saviozzi, Paolo Ceppi, Raffaele A. Calogero, Marco Volante, Marina Longo, Silvia Novello
Rok vydání: 2008
Předmět:
Oncology
Male
Pathology
Lung Neoplasms
DNA Repair
Platinum Compounds
Polymerase Chain Reaction
Severity of Illness Index
Carboplatin
Carcinoma
Non-Small-Cell Lung
Gene expression
Prospective cohort study
Etoposide
Aged
80 and over
Univariate analysis
Excision repair cross-complementing 1 gene
DNA
Neoplasm
Middle Aged
Prognosis
DNA-Binding Proteins
Gene Expression Regulation
Neoplastic
Isoenzymes
Survival Rate
Topoisomerase IIα gene
Italy
Female
medicine.drug
Pulmonary and Respiratory Medicine
Adult
medicine.medical_specialty
Antineoplastic Agents
Small-cell lung cancer
Antigens
Neoplasm
Internal medicine
Ribonucleotide reductase M1 gene
medicine
Carcinoma
Biomarkers
Tumor
Humans
Survival rate
Aged
Retrospective Studies
business.industry
Retrospective cohort study
medicine.disease
Endonucleases
DNA Topoisomerases
Type II
ERCC1
Cisplatin
Pharmacogenomics
business
Follow-Up Studies
Zdroj: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 3(6)
ISSN: 1556-1380
Popis: Hypothesis Aim of the study was to quantify ERCC1, RRM1, and TopoIIα 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 ( R s = 0.34, p = 0.0011) was found. According to response to treatment, it was found that lower TopoIIα expression was associated to a better response in LD patients ( p = 0.025) and, more interestingly, those who had a complete response had lower TopoIIα 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 TopoIIα 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 TopoIIα in ED patients. Conclusions ERCC1 and TopoIIα 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.
Databáze: OpenAIRE
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