Excision repair cross complementing-1 and topoisomerase IIalpha gene expression in small-cell lung cancer patients treated with platinum and etoposide: a retrospective study.
OBJECTIVE
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.
Thoracic Oncology Unit, University of Torino, S. Luigi Hospital, Orbassano (Torino), Italy.
Paolo
P
Ceppi
Marina
M
Longo
Marco
M
Volante
Silvia
S
Novello
Susanna
S
Cappia
Elisa
E
Bacillo
Giovanni
G
Selvaggi
Silvia
S
Saviozzi
Raffaele
R
Calogero
Mauro
M
Papotti
Giorgio V
GV
Scagliotti
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D016190:Carboplatin / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D002945:Cisplatin / Q000627:therapeutic use; D004260:DNA Repair; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D004720:Endonucleases / Q000096:biosynthesis / Q000235:genetics*; D005047:Etoposide / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007527:Isoenzymes; D007558:Italy / Q000453:epidemiology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D017671:Platinum Compounds / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012189:Retrospective Studies; D012720:Severity of Illness Index; D015996:Survival Rate
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D017671:Platinum Compounds; D005047:Etoposide; D016190:Carboplatin; C071447:ERCC1 protein, human; D004720:Endonucleases; D004250:DNA Topoisomerases, Type II; D002945:Cisplatin