Four-gene expression model predictive of lymph node metastases in oral squamous cell carcinoma.

BACKGROUND: Previous knowledge of cervical lymph node compromise may be crucial to choose the best treatment strategy in oral squamous cell carcinoma (OSCC). Here we propose a set four genes, whose mRNA expression in the primary tumor predicts nodal status in OSCC, excluding tongue. MATERIAL AND METHODS: We identified differentially expressed genes in OSCC with and without compromised lymph nodes using Differential Display RT-PCR. Known genes were chosen to be validated by means of Northern blotting or real time RT-PCR (qRT-PCR). Thereafter we constructed a Nodal Index (NI) using discriminant analysis in a learning set of 35 patients, which was further validated in a second independent group of 20 patients. RESULTS: Of the 63 differentially expressed known genes identified comparing three lymph node positive (pN +) and three negative (pN0) primary tumors, 23 were analyzed by Northern analysis or RT-PCR in 49 primary tumors. Six genes confirmed as differentially expressed were used to construct a NI, as the best set predictive of lymph nodal status, with the final result including four genes. The NI was able to correctly classify 32 of 35 patients comprising the learning group (88.6%; p = 0.009). Casein kinase 1alpha1 and scavenger receptor class B, member 2 were found to be up regulated in pN + group in contrast to small proline-rich protein 2B and Ras-GTPase activating protein SH3 domain-binding protein 2 which were upregulated in the pN0 group. We validated further our NI in an independent set of 20 primary tumors, 11 of them pN0 and nine pN + with an accuracy of 80.0% (p = 0.012). CONCLUSIONS: The NI was an independent predictor of compromised lymph nodes, taking into the consideration tumor size and histological grade. The genes identified here that integrate our "Nodal Index" model are predictive of lymph node metastasis in OSCC.

Smad2 and Smad6 as predictors of overall survival in oral squamous cell carcinoma patients.

BACKGROUND: To test if the expression of Smad1-8 mRNAs were predictive of survival in patients with oral squamous cell carcinoma (SCC). PATIENTS AND METHODS: We analyzed, prospectively, the expression of Smad1-8, by means of Ribonuclease Protection Assay in 48 primary, operable, oral SCC. In addition, 21 larynx, 10 oropharynx and 4 hypopharynx SCC and 65 matched adjacent mucosa, available for study, were also included. For survival analysis, patients were categorized as positive or negative for each Smad, according to median mRNA expression. We also performed real-time quantitative PCR (QRTPCR) to asses the pattern of TGFbeta1, TGFbeta2, TGFbeta3 in oral SCC. RESULTS: Our results showed that Smad2 and Smad6 mRNA expression were both associated with survival in Oral SCC patients. Cox Multivariate analysis revealed that Smad6 positivity and Smad2 negativity were both predictive of good prognosis for oral SCC patients, independent of lymph nodal status (P = 0.003 and P = 0.029, respectively). In addition, simultaneously Smad2- and Smad6+ oral SCC group of patients did not reach median overall survival (mOS) whereas the mOS of Smad2+/Smad6- subgroup was 11.6 months (P = 0.004, univariate analysis). Regarding to TGFbeta isoforms, we found that Smad2 mRNA and TGFbeta1 mRNA were inversely correlated (p = 0.05, R = -0.33), and that seven of the eight TGFbeta1+ patients were Smad2-. In larynx SCC, Smad7- patients did not reach mOS whereas mOS of Smad7+ patients were only 7.0 months (P = 0.04). No other correlations were found among Smad expression, clinico-pathological characteristics and survival in oral, larynx, hypopharynx, oropharynx or the entire head and neck SCC population. CONCLUSION: Smad6 together with Smad2 may be prognostic factors, independent of nodal status in oral SCC after curative resection. The underlying mechanism which involves aberrant TGFbeta signaling should be better clarified in the future.

Epidemiological and histopathological data and E-cadherin-like prognostic factors in early carcinomas of the tongue and floor of mouth.

Despite recent advances in diagnosis and treatment, overall survival of people with squamous cell carcinomas of the tongue and mouth floor continues to be low. Prognostic information is essential for improved evaluation and treatment. A molecular approach is necessary for a better understanding of cancer. We analyzed 50 patients with early squamous cell carcinoma (stages I and II - AJCC, 1997), who were surgically treated in head and neck departments at Heliopolis Hospital and Santa Casa in São Paulo, Brazil. We searched for epidemiological and pathological behaviors that could be involved in tumor recurrence and the influence of cellular adhesion loss in patient outcome. We established two groups: patients with disease recurrence within 3 years of follow-up and patients with no cancer recurrence in this period. Significant prognostic variables included age, daily alcohol intake, neural invasion and maximum tumor thickness. Our findings are similar to other published data in which younger patients have a better prognosis. The odds ratio for neural invasion was low but was significant for thickness. No significant difference was observed among groups in E-cadherin expression. Our data suggest that 3 and 5mm are the prognostic determinants of thickness. E-cadherin mutation was not related to recurrences but was associated with locally aggressive invasion patterns.

Autopercepção da desvantagem vocal (VHI) e qualidade de vida relacionada à deglutição (SWAL-QDL) de pacientes laringectomizados totais / Voice handicap (VHI) self perception and quality-of-life related to swallowing (SWAL-QOL) of total laryngectomees

Objetivo: avaliar o índice de desvantagem vocal e a qualidade de vida (QV) relacionada à deglutição de pacientes laringectomizados totais. Método: estudo prospectivo que utilizou o questionário VHI (Voice Handicap Index), composto por 3 domínios: funcional, físico e emocional. Para avaliar a QV relacionada à deglutição foi utilizado o questionário SWAL-QOL (Quality of Life in Swallowing Disorders), composto por 10 domínios, como: fardo, desejo, freqüência de sintomas, seleção de alimentos, comunicação, medo, saúde mental, função social, sono e fadiga. A análise estatística consistiu de distribuição de freqüência e as medidas de tendência central e da variabilidade para as variáveis numéricas. Resultados: 12 pacientes com idade média de 59,6 anos, 58,3% foram submetidos à cirurgia e radioterapia pós-operatória, com dosagem média de 6634cGy. O tempo decorrido do término do tratamento oncológico ao momento da investigação variou de 3 a 41 meses, no momento do estudo todos os pacientes se alimentavam por via oral exclusiva e se comunicavam pela associação da fala articulada, de gestos e da escrita. Em relação à desvantagem vocal a média das pontuações foram 22 para o domínio funcional, 17 para o físico, 14,3 para o emocional e 53,5 para o global. O SWAL-QOL teve médias que variaram entre 53 a 85,4. Conclusão: os resultados demonstraram alterações de grau moderado em relação à auto-percepção da desvantagem vocal e a QV relacionada à deglutição.

Objective: the aim of this study was to evaluate the voice handicap index and the quality of life in swallowing disorders among patinets who underwent total laryngectomy. Methods: prospective study using VHI (Voice Handicap Index) questionnaire with three domains: functional, physic and emotional. The higher the score, the worse is the voice handicap. To evaluate the quality of life in swallowing disorders the SWAL-QOL questionnaire was used (with 44 questions that considers 10 domins: burden, eating desire, symptom frequency, food selection, communication, fear, mental health, social functioning, sleep, fatigue). The answers were converted into a score ranging from 0 to 100, being 0 the worst score and 100 the best one. Statistical analysis conssted of a descriptive analysis of the frequencies for hte categorical variables as well as the variability and the centrla tendency measures for the numerical variables. Results: 12 patients (mean age 59.6 years old) were evaluated. At the moment of the application of the questionnaires all the patients had exclusive oral intake and communication by associated articulated speech, gesticulation and writing. In relation to voice handicap the mean score were 22 to functional domain, 17 to physic, 14.3 to the emotional and 53.5 to global. The SWAL-QOL ranged from 53 to 85.4. Conclusion: the results showed moderate alterations concerning to self perception of the voice handicap and the quality of life related to swallowing.

Hábitos orais de sucção: estudo piloto em população de baixa renda / Suction oral habits: initial study in low income population

Habitos orais de sucção tem sido fonte de estudo pelos danos que podem causar em toda morfologia e função do sistema estomatognático, sendo comumente iniciados e observados na infancia. Fatores emocionais e nutricionais podem contribuir para a manifestação desses habitos. OBJETIVO: Verificar alterações fonoaudiologicas, odontologicas e otorrinolaringol¢gicas em crianças de baixa renda portadoras de hábitos orais de sucção. FORMA DE ESTUDO: Clinico retrospectivo näo randomizado. MATERIAL E METODO: Foram avaliadas nove crianças (01 menino e 08 meninas) com idades entre 5 a 9 anos durante o I Mutiräo da Comunicação realizado no Hosphel, São Paulo, no dia 27 de outubro de 2001. RESULTADOS: O disturbio fonoaudiologico mais comum foi o articulat¢rio (55,56 por cento), seguido pelo disturbio de motricidade oral (33,33 por cento). A mordida aberta esteve presente em 8 casos (88,89 por cento). Com relação ao tipo de respiração apresentou-se com 7 casos com respiração bucal (77,78 por cento). CONCLUSOES: Os hábitos orais foram capazes de promover alterações fonoaudiologicas, odontologicas e otorrinolaringologicas. Medidas de promoção de saúde devem ser lançadas para crianças de baixa renda visando eliminar os fatores responsáveis pela origem dos habitos orais viciosos de sucção, tais como: alimentação e educação. Alem de medidas de tratamento multidisciplinar, devem ser estabelecidas fonoaudiologia, ortodontia, otorrinolaringologia em saude publica, solucionando o paradigma das alterações decorrentes desses habitos comumente perceptiveis na infancia

Qualidade de vida e prognóstico nos carcinomas epidermóides de cabeça e pescoço / Quality of life and prognosis of squamous cell carcinoma of the head and neck

Objetivo: avaliar um questionário para mensuraçäo da qualidade de vida e sua relaçäo com o prognóstico em pacientes com câncer de cabeça e pescoço. Forma de estudo: prospectivo clínico. Material e Método: estudo de 31 pacientes com carcinoma epidermóide de vias aerodigestivas superiores atendidos no Departamento de Cirurgia de Cabeça e Pescoço e Otorrinolaringologia do Hospital Heliópolis, Hosphel, Säo Paulo, no período de agosto de 1999 a novembro de 2000. Na avaliaçäo da qualidade de vida empregou-se o questionário QLQ-C30 e o módulo QLQ-H&N35, ambos fornecidos pela EORTC, sendo realizada previamente ao tratamento. Foi avaliada a diferença de pontuaçäo entre os pacientes que apresentavam doença controlada e aqueles com recidiva nos primeiros 12 meses após o tratamento. Resultados: foi observada uma diferença significativa na pontuaçäo entre os pacientes assintomáticos e aqueles com recidiva da doença nas escalas relacionadas à fadiga, dificuldade de comer em público e qualidade de vida global (p <= 0,05). A pontuaçäo obtida neste grupo de pacientes foi semelhante à observada em outras populaçöes. Conclusäo: a qualidade de vida prévia ao tratamento pode constituir um indicador prognóstico para os pacientes com câncer de cabeça e pescoço