BRCA1 and γH2AX as independent prognostic markers in oral squamous cell carcinoma
Joao Paulo Oliveira-Costa1,2, Lucinei Roberto Oliveira3, Juliana Silva Zanetti1, Giorgia Gobbi da Silveira1, Marcilei Eliza Chavichiolli Buim2, Sergio Zucoloto1†, Alfredo Ribeiro-Silva1, Fernando Augusto Soares2
1 Department of Pathology and Forensic Medicine, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil
2 Department Anatomic Pathology, AC Camargo Cancer Center, Sao Paulo, Brazil
3 Department of Oral Pathology, School of Dentistry, Vale do Rio Verde University (Unincor), Tres Coracoes, Brazil
† Deceased
Correspondence:
Joao Paulo Oliveira-Costa, email:
Correspondence:
Fernando Augusto Soares, email:
Keywords: BRCA1, H2AX, oral squamous cell carcinoma, DNA damage, prognostic factor
Received: March 05 2014 Accepted: May 31, 2014 Published: June 1, 2014
Abstract
Oral squamous cell carcinomas (OSCC) are believed to originate from sequential mutations that can develop as a consequence of genetic instability acquired over time. BRCA1 are linked to DNA recombination and repair processes, being of importance for its role in regulation of RAD51 and H2AX (γH2AX). The aim of this study was to investigate the relationship between BRCA1 expression status and evaluate its prognostic impact. We selected from 150 OSCC patients, and evaluated BRCA1 expression in OSCC by immunohistochemistry and qRT-PCR, comparing its expression with homologous recombination markers (RAD51, γH2AX and p53), clinicopathological and survival data. Expression of BRCA1 was observed in 61 cases (43.88%) and was related to tumor size (T stage) (p=0.001), and gender (p=0.017). mRNA from BRCA1 showed a borderline relationship with perineural invasion (p=0.053). BRCA1 [p=0.030; HR: 2.334 (C.I.: 1.087-5.012)], γH2AX [p=0.045; HR: 0.467 (C.I.: 0.222- 0.628)] and gender [p=0.001; HR: 10.386 [(C.I.: 2.679-10.623)] were independent prognostic factors for DSS. BRCA1 and γH2AX expression by OSCC cells are associated with reduced overall survival time, independent of other variables in patients, as well as gender, and our findings shed some light about DSB markers in OSCC and its role as prognostic factors.
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