RT Journal Article
SR Electronic
T1 Prognostic Significance of <em>ERCC1</em>, <em>RRM1</em> and <em>BRCA1</em> in Surgically-treated Patients with Non-small Cell Lung Cancer
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 5003
OP 5010
VO 32
IS 11
A1 MARTIN PESTA
A1 VLASTIMIL KULDA
A1 ONDREJ FIALA
A1 JARMIL SAFRANEK
A1 ONDREJ TOPOLCAN
A1 GABRIELA KRAKOROVA
A1 RADIM CERNY
A1 MILOS PESEK
YR 2012
UL http://ar.iiarjournals.org/content/32/11/5003.abstract
AB Chemotherapy is an important modality of treatment for non-small cell lung cancer (NSCLC). Recent studies have shown that assessment of predictive molecular markers could be helpful for estimation of the response rate to chemotherapy. The aim of our study was to assess the relation of mRNA levels of DNA repair genes excision repair cross-complementary group 1 (ERCC1), ribonucleotide reductase subunit M1 (RRM1) and breast cancer 1 (BRCA1), in surgically-resected tumor tissues from patients who underwent adjuvant chemotherapy, to the disease-free interval (DFI) and overall survival (OS). We investigated if potential residual tumor cells after resection reflect properties of the primary tumor and response to chemotherapy according to the level of predictive markers with respect to current knowledge. Patients and Methods: We studied a group of 90 patients with NSCLC who had undergone curative lung resection; 59 of them were subsequently treated with adjuvant chemotherapy, DFI and OS were evaluated only in this subgroup. Quantitative estimation of mRNA of selected genes in paired (tumor and control)-lung tissue samples was performed by real-time reverse transcription-polymerase chain reaction (RT-PCR). Results: We found a significantly lower mRNA expression of ERCC1 (p&lt;0.001) and RRM1 (p=0.023) in NSCLC tumor tissues compared to normal lung tissues. Comparing expression in histological subtypes, we recorded higher mRNA expression of ERCC1 (p=0.021), RRM1 (p=0.011) and BRCA1 (p=0.011) in adenocarcinoma than in squamous cell carcinoma (SCC). Differences in DFI and OS were found only in specific subgroups according to tumor type and stage. We found longer OS for patients with adenocarcinoma with higher expression of the RRM1 mRNA (p=0.002), and for patients with SCC with higher expression of the BRCA1 mRNA (p=0.041). In patients with NSCLC of stage III, we found longer DFI in those with higher expression of RRM1 (p=0.004) and ERCC1 (p=0.038). Conclusion: Patients who had been treated with adjuvant chemotherapy and had shown lower expression of repair genes had adverse prognosis. We observed that the assessment of DNA repair gene level in primary tumors treated by surgical resection had prognostic significance and did not predict response to adjuvant chemotherapy.