title: ERCC1 protein, mRNA expression and T19007C polymorphism as prognostic markers in head and neck squamous cell carcinoma patients treated with surgery and adjuvant cisplatin-based chemoradiation.
abstract: Adjuvant cisplatin-based chemoradiation improves survival in HNSCC patients presenting with risk features. ERCC1 (excision repair cross-complementation group 1) is associated with resistance to chemo- and radiation therapy and may have a prognostic value in HNSCC patients. Here we studied ERCC1 expression and the polymorphism T19007C as prognostic markers in these patients. This is a retrospective and translational analysis, where ERCC1 protein expression was evaluated by immunohistochemistry, using an H-score, and mRNA expression was determined by RT-PCR. T19007C genotypes were detected by PCR-RFLP carried out using DNA template extracted from normal lymph nodes. A high H-score was seen in 32 patients (54%), who presented better 5-year overall survival (5-y OS: 50% vs. 18%, HR 0.43, p=0.026). Fifteen out of 45 patients (33%), with high mRNA expression, presented better 5-year overall survival (OS) (86% vs. 30%, HR 0.26, p=0.052). No OS difference was detected among T19007C genotypes. High H-score and mRNA expression remained significant as favorable prognostic factors in a multivariate analysis. Collectively, our results suggest that high ERCC1 expression seems to be associated with better OS rates in HNSCC patients submitted to adjuvant cisplatin-based chemoradiation.
authors.affiliation: Instituto do Câncer do Estado de São Paulo, Clinical Oncology, Av. Dr. Arnaldo 251, 5th floor, São Paulo, SP 01246-000, Brazil. gilberto.castro@usp.br
authors.forename: Gilberto
authors.initials: G
authors.lastname: De Castro
authors.forename: Fatima Solange
authors.initials: FS
authors.lastname: Pasini
authors.forename: Sheila Aparecida Coelho
authors.initials: SA
authors.lastname: Siqueira
authors.forename: Alberto Rossetti
authors.initials: AR
authors.lastname: Ferraz
authors.forename: Rosangela Correa
authors.initials: RC
authors.lastname: Villar
authors.forename: Igor Moysés Longo
authors.initials: IM
authors.lastname: Snitcovsky
authors.forename: Miriam Hatsue Honda
authors.initials: MH
authors.lastname: Federico
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000175:diagnosis / Q000235:genetics / Q000401:mortality / Q000628:therapy; D002294:Carcinoma, Squamous Cell; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D013505:Digestive System Surgical Procedures; D004720:Endonucleases / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000401:mortality / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D018307:Neoplasms, Squamous Cell / Q000175:diagnosis / Q000235:genetics / Q000401:mortality / Q000628:therapy; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D018714:Radiotherapy, Adjuvant; D012189:Retrospective Studies; D000077195:Squamous Cell Carcinoma of Head and Neck; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin