RESUMEN
DNA repair is a key determinant in the cellular response to therapy and tumor repair status could play an important role in tailoring patient therapy. Our goal was to evaluate the mRNA of 13 genes involved in different DNA repair pathways (base excision, nucleotide excision, homologous recombination, and Fanconi anemia) in paraffin embedded samples of triple negative breast cancer (TNBC) compared to luminal A breast cancer (LABC). Most of the genes involved in nucleotide excision repair and Fanconi Anemia pathways, and CHK1 gene were significantly less expressed in TNBC than in LABC. PARP1 levels were higher in TNBC than in LABC. In univariate analysis high level of FANCA correlated with an increased overall survival and event free survival in TNBC; however multivariate analyses using Cox regression did not confirm FANCA as independent prognostic factor. These data support the evidence that TNBCs compared to LABCs harbour DNA repair defects.
Asunto(s)
Reparación del ADN/genética , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Neoplasias de la Mama Triple Negativas/genética , Adulto , Anciano , Anciano de 80 o más Años , Anemia de Fanconi/genética , Femenino , Recombinación Homóloga/genética , Humanos , Persona de Mediana Edad , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores de Estrógenos/metabolismo , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
PURPOSE: To determine the prognostic importance of p16 and human papillomavirus (HPV) in patients with oropharyngeal cancer treated on a phase III concurrent chemoradiotherapy trial. PATIENTS AND METHODS: Patients with stage III or IV head and neck squamous cell cancer were randomly assigned to concurrent radiotherapy and cisplatin with or without tirapazamine. In this substudy, analyses were restricted to patients with oropharyngeal cancer. p16 was detected by immunohistochemistry, and HPV was detected by in situ hybridization and polymerase chain reaction. RESULTS: Slides were available for p16 assay in 206 of 465 patients, of which 185 were eligible, and p16 and HPV were evaluable in 172 patients. One hundred six (57%) of 185 were p16-positive, and in patients evaluable for both p16 and HPV, 88 (86%) of 102 p16-positive patients were also HPV-positive. Patients who were p16-positive had lower T and higher N categories and better Eastern Cooperative Oncology Group (ECOG) performance status. p16-positive tumors compared with p16-negative tumors were associated with better 2-year overall survival (91% v 74%; hazard ratio [HR], 0.36; 95% CI, 0.17 to 0.74; P = .004) and failure-free survival (87% v 72%; HR, 0.39; 95% CI, 0.20 to 0.74; P = .003). p16 was a significant prognostic factor on multivariable analysis (HR, 0.45; 95% CI, 0.21 to 0.96; P = .04). p16-positive patients had lower rates of locoregional failure and deaths due to other causes. There was a trend favoring the tirapazamine arm for improved locoregional control in p16-negative patients (HR, 0.33; 95% CI, 0.09 to 1.24; P = .13). CONCLUSION: HPV-associated oropharyngeal cancer is a distinct entity with a favorable prognosis compared with HPV-negative oropharyngeal cancer when treated with cisplatin-based chemoradiotherapy.