RESUMEN
OBJECTIVE: This study aimed to link expression patterns of AQP1, AQP5, Bcl-2 and p16 to clinicopathological characteristics of oro-hypopharyngeal squamous cell carcinomas. METHODS: Immunohistochemical expression of AQP1, AQP5, Bcl-2 and p16 was investigated in 107 consecutive oro-hypopharyngeal squamous cell carcinoma cases. Molecular interrelationship and correlations with clinicopathological parameters and survival were computed. RESULTS: AQP1 was expressed exclusively by a subgroup of basaloid-like squamous cell carcinomas. AQP5 was detected in 25.2 per cent of the samples, showing significant association with the absence of p16 and Bcl-2 (p = 0.018; p = 0.010). In multivariate analysis, overexpression of p16 was significantly correlated with favourable overall survival (p = 0.014). CONCLUSION: AQP5 defined a subset of patients with Bcl-2-negative and p16-negative tumours with a poor clinical outcome. AQP1 was found to be a marker of a subgroup of aggressive basaloid-like squamous cell carcinomas. These findings suggest that AQP1 and AQP5 are interesting candidates for further studies on risk group classification and personalised treatment of oro-hypopharyngeal squamous cell carcinomas.
Asunto(s)
Acuaporina 1/genética , Acuaporina 5/genética , Carcinoma de Células Escamosas/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Hipofaríngeas/genética , Proteínas de Neoplasias/genética , Proteínas Proto-Oncogénicas c-bcl-2/genética , Acuaporina 1/biosíntesis , Acuaporina 5/biosíntesis , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Inhibidor p16 de la Quinasa Dependiente de Ciclina , ADN de Neoplasias/genética , Femenino , Genotipo , Humanos , Neoplasias Hipofaríngeas/metabolismo , Neoplasias Hipofaríngeas/patología , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/biosíntesis , Pronóstico , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesisRESUMEN
BACKGROUND: Expression of the antiapoptotic and antiproliferative protein B-cell lymphoma 2 (Bcl-2) has been repeatedly shown to be associated with better locoregional control and patients' survival in oropharyngeal squamous cell carcinoma (OSCC). A regulatory (-938C>A) single-nucleotide polymorphism (SNP) in the inhibitory P2 BCL2 gene promoter generates significantly different BCL2 promoter activities and has been associated with outcome in different malignancies. The aim of the present study was to analyze the possible influence of the (-938C>A) SNP on survival of patients suffering from OSCC. MATERIALS AND METHODS: One hundred and thirty-three patients with primary OSCC were retrospectively investigated. Bcl-2 expression of tumor cells was demonstrated by means of immunohistochemistry. Both the Bcl-2 expression and the (-938C>A) genotypes were correlated with the patients' survival. RESULTS: The (-938C>A) SNP was significantly related to Bcl-2 expression (P = 0.008). Kaplan-Meier curves revealed a significant association of the -938 SNP with relapse-free (P = 0.0283) and overall survival (P = 0.0247). Multiple Cox regression identified the BCL2 (-938CC) genotype as an independent prognostic factor for relapse [hazard ratio (HR) 1.898, P = 0.021] as well as for death in OSCC patients (HR 1.897, P = 0.013). CONCLUSIONS: The (-938C>A) SNP represents a potential novel prognostic marker in patients with OSCC that could help to identify a group of patients at high risk for relapse and death.
Asunto(s)
Carcinoma de Células Escamosas/genética , Genes bcl-2/genética , Recurrencia Local de Neoplasia/genética , Neoplasias Orofaríngeas/genética , Anciano , Carcinoma de Células Escamosas/mortalidad , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Orofaríngeas/mortalidad , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Proteínas Proto-Oncogénicas c-bcl-2/genética , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
The transcription factor, nuclear factor-kappaB (NF-kappaB) is known to play a major role in immune response, inflammation and, via apoptosis and proliferation, also in oncogenesis. Transcription of NFKB1, which encodes the subunit p50/p105 of NF-kappaB, seems to be influenced by an insertion/deletion polymorphism in its promoter region. Accordingly, the goal of this study is to investigate whether this polymorphism can serve as a putative prognostic marker in patients with Squamous Cell Carcinomas of the Head and Neck region (HNSCC). The prognostic value of the -94ins/delATTG NFKB1 promoter polymorphism was analyzed in an unselected series of patients treated with curative intent for HNSCC, including all tumor stages with different therapeutical regimens. Genotyping was performed by means of pyrosequencing, using DNA from paraffin-embedded tissue samples from 364 patients with a median follow-up of 61 (2-143) months. The various genotypes were correlated with relapse-free and overall survival, as well as risk, compared to healthy volunteers. The NFKB1 polymorphism was not related to risk of HNSCC. Kaplan-Meier curves revealed no significant association between the -94ins/delATTG alleles and survival or disease progression of patients with HNSCC. In conclusion, the results suggest that the investigated NFKB1 promoter polymorphism has no prognostic impact on risk or clinical course in HNSCC.