RESUMO
BACKGROUND: HPV16 is the most prevalent genotype in oropharyngeal squamous cell carcinomas (OPSCCs), but there are few information about intratype variants prevalence and their clinical relevance in these tumors. Moreover, since HPV DNA detection alone is not sufficient to determine a favorable prognosis for OPSCCs, additional diagnostic/prognostic biomarkers are necessary. OBJECTIVES: To assess the prevalence of HPV intratype variants and evaluate the role of HPV16 DNA methylation as prognostic marker in OPSCCs. STUDY DESIGN: We analyzed 81 biopsies of OPSCCs for HPV detection and genotyping with a pyrosequencing-based HPV DNA-test. We also quantified viral DNA methylation frequency in the LCR by pyrosequencing in patients with transcriptionally-active HPV16-infection, analyzing it in function of available clinical/virological data. RESULTS: The overall HPV prevalence was 74.1% and HPV16 was confirmed the most prevalent genotype (51/60, 85.0%). Interestingly, we detected, for the first time, HPV16 African variants in 10/51 cases (19.6%), pointing out their clinical relevance also out of the anogenital district. Regarding viral DNA methylation, the E2BS1 showed a significantly higher mean methylation frequency compared to E2BS3/4, as previously observed in high-grade precancerous lesions of the uterine cervix. On the other hand, patient with a mean methylation frequency in the early promoter >10% showed only a tendency to have a worse prognosis. CONCLUSIONS: Our results highlight both the involvement of HPV16 African variants in OPSCCs development and the necessity of further studies to deepen the role of viral methylation in these tumors, in order to better define similarities/differences compared to cervical cancer.
Assuntos
Carcinoma de Células Escamosas/virologia , Metilação de DNA , DNA Viral , Variação Genética , Papillomavirus Humano 16/genética , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Orofaríngeas/epidemiologia , Neoplasias Orofaríngeas/patologia , Infecções por Papillomavirus/complicações , Prevalência , Regiões Promotoras Genéticas , Fatores de Risco , Análise de SobrevidaRESUMO
OBJECTIVE: To correlate the presence of BRAF V600E mutation with clinicopathological parameters. STUDY DESIGN: Case-control study. SETTING: BRAF mutation represents the most common oncogenic event in sporadic papillary thyroid cancer (PTC). There are, however, significant discrepancies regarding the overall frequency and its relationship with clinicopathological parameters of poor outcome. We analyzed BRAF mutation in a cohort of patients affected by PTCs to identify its association with clinical variables. SUBJECTS AND METHODS: We analyzed retrospectively a series of 304 patients, treated for PTC from 1999 to 2011 at Bologna University Hospital. We searched BRAF mutation by reverse transcription polymerase chain reaction (PCR) followed by PCR and direct sequencing. RESULTS: BRAF mutation was found in 77.4% of classical PTCs, 31.9% of the follicular variant, and 72.2% of high tall cell PTCs, being significantly associated, at univariate analysis, with recurrence, stage, multicentricity, histologic subtype, extrathyroidal extension, nodule dimension, body mass index, and American Thyroid Association (ATA) risk stratification. Furthermore, higher T, but not N or M, stage was associated with BRAF mutation. In the multivariate analysis, the BRAF mutation was significantly associated only with the ATA risk stratification, in turn showing a significant negative association with recurrence-free survival time with Cox multivariate analysis. CONCLUSION: Our results indicate that BRAF mutation identifies a subset of PTC with increased risk of recurrence. The presence of BRAF mutation might be a valuable diagnostic and prognostic marker of the disease. To confirm the diagnostic usefulness of this marker, further studies should be carried out.
Assuntos
Carcinoma/genética , Mutação/genética , Recidiva Local de Neoplasia/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias da Glândula Tireoide/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Carcinoma/mortalidade , Carcinoma/cirurgia , Carcinoma Papilar , Estudos de Casos e Controles , Criança , Intervalos de Confiança , DNA de Neoplasias/análise , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/mortalidade , Reação em Cadeia da Polimerase/métodos , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Estatísticas não Paramétricas , Taxa de Sobrevida , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/cirurgia , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: The aim of this study was to assess a prospective, randomized clinical trial (RCT) comparing neurostimulation with laryngeal palpation (NSLP) of recurrent laringeal nerve (RLN) alone with NSLP associated with laryngeal neuromonitoring (LNM) to evaluate the ability of LNM in reducing the rates of RLN palsy. METHODS: In all, 250 consecutive patients scheduled to have thyroidectomy were randomized to NSLP alone (NSLP group) or NSLP with LNM (LNM group). The primary endpoint was to assess the rate of RLN palsy. RESULTS: The incidence of palsy was 2.7% in the LMN group and 2.6% in the NSLP group. No significant statistical difference between the groups was observed either for permanent or for transient paralysis (respectively, Fisher's Exact test: p = 1.0 and p = 1.0). CONCLUSIONS: This RCT shows that the use of LNM during thyroidectomy does not reduce the rates of recurrent laryngeal injuries compared with NSLP alone.
