title: ERCC1 and topoisomerase I expression in small cell lung cancer: prognostic and predictive implications.
abstract: Small cell lung cancer is the most aggressive lung cancer subtype. The standard             treatment approach is based on cisplatin regimens. Although response rates to             treatment are approximately 60-80%, the median survival is still very poor. Excision             repair cross complementation group 1 (ERCC1) is an enzyme that removes cisplatin-induced             DNA adducts and has been related with prognosis and cisplatin response. Topotecan             is the standard treatment as second-line therapy and it is an inhibitor of topoisomerase             I (TOP I). We selected 76 patients with small cell lung (SCLC) to analyze the             ERCC1 and TOP I mRNA expression. ERCC1 was studied both by quantitative PCR and             immunohistochemistry. A significant association was found between the inmunohistochemistry             expression of ERCC1 and the lack of platinum response (p=0.001). Moreover, low             levels of TOP I RNA were shown to be linked to cisplatin response (p=0.002). In             the survival analysis, a significant correlation between a better PFS with a low             TOP I RNA expression as well as a negative ERCC1 inmunostaining were found, in             both cases with a significant p-value (p=0.02 and 0.009, respectively). In summary,             our results suggest the use of ERCC1 immunohistochemistry and TOP I mRNA analysis             to predict cisplatin response and prognosis in SCLC patients.
authors.affiliation: Department of Medical Oncology, Infanta Sofía Hospital, 28702 San Sebastian De Los Reyes, Madrid, Spain. mariasereno75@gmail.com
authors.forename: Maria
authors.initials: M
authors.lastname: Sereno
authors.forename: Paloma
authors.initials: P
authors.lastname: Cejas
authors.forename: Víctor
authors.initials: V
authors.lastname: Moreno
authors.forename: Cristóbal
authors.initials: C
authors.lastname: Belda-Iniesta
authors.forename: Rocio
authors.initials: R
authors.lastname: López
authors.forename: Manuel
authors.initials: M
authors.lastname: Nistal
authors.forename: Jaime
authors.initials: J
authors.lastname: Feliu
authors.forename: Javier
authors.initials: J
authors.lastname: De Castro Carpeño
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D004264:DNA Topoisomerases, Type I / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism*; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D014158:Transcription, Genetic; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D004268:DNA-Binding Proteins; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D016190:Carboplatin; C071447:ERCC1 protein, human; D004720:Endonucleases; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human; D002945:Cisplatin