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.
Highlights
Oral squamous cell carcinoma (OSCC) are believed to originate from sequential mutations that can develop as a consequence of progressive genetic instability acquired over time
To the best of our knowledge, the present study is the first study to report the immunoexpression of BRCA1 and γH2AX in OSCC, and to show an important role for these markers as independent predictors of disease-specific survival
There was no influence in disease-free survival for the expression of both markers
Summary
Oral squamous cell carcinoma (OSCC) are believed to originate from sequential mutations that can develop as a consequence of progressive genetic instability acquired over time. BRCA1 and BRCA2 are linked to DNA recombination and repair processes, being of particular importance for the role in regulation of RAD51 activity www.impactjournals.com/oncoscience [6,7], which is recruited by a damage signaling protein, phosphorylated H2AX (γH2AX). An inability to repair DSB through HR leads to increased use of the alternative error-prone repair pathways (NHEJ and SSA) with a subsequent increase in deletions, translocations and chromosomal instability. This genomic instability provided by such mechanisms probably underlies the cancer predisposition caused by loss-of-function mutations in BRCA1 or BRCA2 [6,7]
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