Topoisomerases são enzimas nucleares que participam na regulação da estrutura do DNA nas células eucarióticas. A topoisomerase III é o mais novo membro da família das topoisomerases. Seu papel no desenvolvimento dos tumores mamários ainda necessita ser investigado. O objetivo do presente estudo foi avaliar a imunoexpressão da topoisomerase III nos carcinomas mamários, e comparar sua expressão com dados clinicopatológicos e marcadores imunohistoquímicos clássicos de importância prognóstica nos carcinomas mamários. Utilizando-se tissue microarrays contendo 171 casos de carcinomas ductais mamários primários, foi analisada a expressão imunohistoquímica de topoisomerase III, receptor de estrógeno, receptor de progesterona, HER-2, Ki67, p53 e BRCA-1. Positividade para topoisomerase III foi encontrada em 33,9% dos casos, e sua expressão relacionou-se com metástases à distância (p=0.036) e óbito (p=0.006). Negatividade para topoisomerase III relacionou-se com negatividade para HER=2 (p<0.001), p53 (p<0.001) e BRCA-1 (p=0.001), e com baixa expressão de Ki-67 (p<0.001). Na Análise de Riscos Múltiplos de Cox, a expressão de topoisomerase III foi um significante preditor de sobrevida [razão de risco 3.006 (intervalo de confiança a 95%: 1.582-5.715); p=0.001]. Concluindo, a topoisomerase III pode ser útil na avaliação do prognóstico de pacientes com câncer de mama, além de ser um fator independente de predição da sobrevida. / Topoisomerases are ubiquitous nuclear enzymes that regulate DNA structure in eukaryotic cells. The role of topoisomerase III, the newest member of the topoisomerase family, in the clinical outcome of breast cancer is still poorly understood. This study aims to investigate the immunoexpression of topoisomerase III in breast cancer and its relationships with clinicopathological features and immunohistochemical markers of prognostic significance in breast pathology. Using tissue microarrays containing 171 cases of primary invasive breast cancer, we analyzed the immunoexpression of topoisomerase III, estrogen receptor, progesterone receptor, HER-2, Ki67, p53 and BRCA-1. Immunostaining for topoisomerase III was found in 33.9% of breast carcinomas, and immunopositivity was related with distant metastasis (p=0.036) and death (p=0.006). Decreased expression of topoisomerase III was related with negativity with HER-2 (p<0.001), p53 (p<0.001) and BRCA1 (p=0.001) and low expression of Ki67 (p<0.001). In the multivariate analysis, topoisomerase III expression was a significant predictor of survival [hazard ratio 3.006 (95% confidence interval 1.582-5.715); p=0.001]. In conclusion, topoisomerase III expression can be a useful marker in assessing the prognosis of patients with breast cancer and is an independent predictor of survival.

Os carcinomas de cabeça e pescoço (CECPs) compreendem um grupo de tumores que atingem vários sítios do trato aerodigestivo superior, incluindo cavidade oral, orofaringe, hipofaringe e laringe. Esses carcinomas são clinicamente heterogeneous e resultam de modificações cumulativas em genes que regulam proliferação, migração celular e apoptose. São estimados aproximadamente 500.000 novos casos de CECP anualmente no mundo. No Brasil, cerca de 14.000 novos casos são esperados em 2010, somente para cavidade oral. As taxas de morbidade e mortalidade e as limitações das estratégias terapêuticas enfatizam a necessidade de um melhor entendimento dos padrões moleculares envolvidos na iniciação e na progressão desses tumores, e de abordagens preventivas e terapêuticas efetivas. Infelizmente, apesar da intensa pesquisa nessa área, poucos marcadores moleculares são conhecidos que exibam sensibilidade e especificidade para diagnóstico e prognóstico de CECP. Em um estudo prévio, nós avaliamos dados de três bibliotecas SAGE de carcinoma de laringe com a finalidade de identificar eventos associados ao desenvolvimento e à agressividade de CECP. Utilizando abordagens estatísticas e de Bioinformática, nós identificamos 60 genes com expressão elevada ou reduzida em tumores metastáticos versus não-metastáticos e em ambos os grupos versus tecidos normais. O objetivo do presente estudo foi avaliar a expressão de quatro genes desta lista, os das queratinas 6A (KRT6A) e 19 (KRT19), da mesotelina (MSLN) e da calicreína 8 (KLK8), em um conjunto de 63 carcinomas primários de cabeça e pescoço e suas margens cirúrgicas e em quarto linhagens celulares (Hep-2, FaDu, SCC9 e UM-SSC-38) por RT-PCR em tempo real. Como amostra de referência para as linhagens, foram utilizados queratinócitos orais humanos normais, cultivados sobre uma camada de sustentação de fibroblastos irradiados. Todos os genes exibiram níveis de transcritos reduzidos ou ausentes nas linhagens celulares, exceto MSLN, que mostrou um padrão irregular de expressão. Em tumores primários, os genes KRT19 e MSLN apresentaram expressão diminuída em laringe, o mesmo sendo observado para o gene KLK8 em tumores de língua metastático. Além disso, foi detectada expressão elevada de MSLN e KLK8 em tumores não metastáticos de soalho de boca e expressão reduzida de KRT19 em tumores de soalho de boca e língua metastáticos. Os resultados levantam questões sobre o papel desses genes em processos biológicos associados com a tumorigênese de cabeça e pescoço e sobre sua participação no fenótipo neoplásico. / Head and neck squamous cell carcinomas (HNSCCs) encompass a group of tumors that affect a variety of sites in the upper aero-digestive tract, including oral cavity, oropharynx, hypopharynx and larynx. These carcinomas are clinically heterogeneous and result from cumulative changes in genes that regulate cell proliferation, migration and death. It is estimated that approximately 500,000 new cases of HNSCC are diagnosed worldwide each year. In Brazil, about 14,000 new cases are expected in the year 2010, only in oral cavity. The morbidity and mortality rates and the limitations of therapeutic strategies emphasize the need for a better understanding of the molecular pathways involved in the initiation and progression of these tumors and for effective preventive and therapeutic approaches. Unfortunately, despite intense research, few molecular markers are known to exhibit sensitivity and specificity for the diagnosis or prognosis of HNSCC. In a previous study, we evaluated data from three SAGE libraries of larynx carcinoma in order to identify events associated with the development and aggressiveness of HNSCCs. Using statistical and bioinformatic tools, we identified sixty top-up and 60 top-downregulated genes in metastatic versus non-metastatic tumors and in both these tumors versus normal tissues. The objective of the present study was to evaluate the expression of four genes from this list, keratin 6A (KRT6A), keratin 19 (KRT19), mesothelin (MSLN) and kallikrein 8 (KLK8), in a set of 63 primary carcinomas of head and neck and their surgical margins and in four cell lines (Hep-2, FaDu, SCC9 and UM-SSC-38) by real time RT-PCR. As a reference sample for cell lines, we used normal human oral keratinocytes grown on irradiated fibroblast feeder layer. All genes exhibited no or decreased levels of transcripts in the cell lines, except MSLN, which displayed an irregular pattern of expression. In primary tumors, KRT19 and MSLN genes were downregulated in larynx, and KLK8 in metastatic tongue tumors. In addition, MSLN and KLK8 were upregulated in non-metastatic floor of the mouth tumors and KRT19 was down regulated in metastatic floor of the mouth and tongue tumors. The results open questions about the role of these genes on biological processes related to head and neck tumorigenesis and on neoplastic phenotype.

Resumo: Transição epithelial-mesenquimal (EMT) é a conversão de células epiteliais polarizadas para células migratórias com fenótipo fibroblasto-símile. A EMT está envolvida na progressão e metástase em diversos cânceres nos seres humanos, porém permanece a ser mais bem explorada na literatura veterinária. O objetivo desta pesquisa foi avaliar a imunoexpressão de proteínas relacionadas à EMT nos carcinomas mamários de cadelas (CMCs). Seis proteínas foram avaliadas por meio de imunoistoquímica em 94 amostras de CMCs. Tecidos mamários não neoplásicos de 17 cadelas e amostras de 9 tumores mamários benignos de cadelas foram avaliados de modo a determinar o perfil de imunoexpressão de Snai-1. Características anatomopatológicas foram comparadas com a imunoexpressão de proteínas relacionadas à EMT nos CMCs. A perda de proteínas epiteliais e/ou a aquisição de proteínas mesenquimais foi observada principalmente em neoplasias com evidência de invasão estromal; entretanto, somente foi observada significância estatística quando comparado S100A4 e invasão vascular. Snai-1 foi observado em células luminais de neoplasias simples malignas e em células mioepiteliais de tumores benignos ou malignos de caráter complexo, sendo também significativamente relacionado à baixa de expressão de Caderina-E. Conclui-se que a perda de proteínas epiteliais e/ou a aquisição de proteínas mesenquimais está associada com EMT e pode possuir importante papel na avaliação de CMCs. O padrão único de imunoexpressão de Snai-1 pode ajudar a distinção entre um adenoma e um carcinoma não metastático e aparenta estar relacionado à conversão de células mioepiteliais a um fenótipo mesenquimal completo. A perda de Caderina-E e citoqueratina e a mudança no padrão de imunoexpressão de Snai-1, Caderina-N, S100A4 e MMP-2 indica a ocorrência de EMT em carcinomas mamários de cadelas... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Epithelial-mesenchymal transition (EMT) is defined as switching of polarized epithelial cells to a migratory fibroblastoid phenotype. EMT is known to be involved in the progression and metastasis of various cancers in humans, but this specific process is still little explored in the veterinary literature. The aim of this research was to evaluate the expression of EMT-related proteins in canine mammary carcinomas (CMCs). The expression of six EMT-related proteins in CMC of 94 female dogs was evaluated by immunohistochemistry. Additionally, mammary tissues from 17 female dogs with no history of mammary tumor development and from 9 bitches with benign tumors were evaluated in order to determine Snai-1 immunoexpression patterns. Anatomopathological characteristics were compared with the expression of EMTrelated proteins in CMCs. Loss of epithelial protein and/or acquisition of the expression of mesenchymal proteins were observed, particularly in tumors with evidence of stromal invasion; however, significance was only observed between the S100A4 and vascular invasion. Snai-1 was only expressed in luminal cells of histologically malignant tumors and in myoepithelial cells of benign and malignant complex tumors and was significantly related to E-cadherin loss. In conclusion, loss of epithelial proteins and/or the acquisition of mesenchymal proteins are associated with EMT and may have an important role in the evaluation of CMC patients. The unique immunoexpression pattern of Snai-1 could help to distinguish between an adenoma and a non-metastatic carcinoma and seems to be related to conversion of myoepithelial cells to a complete mesenchymal-like phenotype. Loss of E-cadherin and cytokeratin and change of immunoexpression pattern of Snai-1, N-cadherin, S100A4 and MMP-2 indicate the occurrence of EMT in canine mammary carcinomas and should result in an en bloc resection or a close follow-up. / Orientador: Noeme Souza Rocha / Coorientador: Rafael Malagoli Rocha / Banca: Deilson Elgui de Oliveira / Banca: Geovanni Dantas Cassali / Mestre

Resumo: O carcinoma de células escamosas de cabeça e pescoço é um tumor agressivo e está relacionado com a exposição ao tabaco e ao álcool. A recorrência elevada, a variação na agressividade e as taxas baixas de sobrevivência dessa doença requerem nossos esforços para compreender a sua patogênese e para desenvolver melhores estratégias terapêuticas. No presente estudo, foi investigado se a análise proteômica pode identificar diferenças na expressão protéica entre carcinomas de cabeça e pescoço de diferentes graus de estadiamento. Para alcançar este objetivo, foram otimizados protocolos para extração de proteínas e a técnica de eletroforese bidimensional (2D) foi implantada no laboratório. Os padrões de perfil protéico obtidos foram analisados em oito amostras de carcinoma oral e duas de orofaringe (oito procedentes de tumores com metástases em linfonodos regionais e dois sem metástases) e em 17 amostras aparentemente normais de margens cirúrgicas. As variações qualitativas e quantitativas detectadas nos perfis protéicos de ambos os grupos foram consistentes e oito proteínas foram identificadas após análise por espectrometria de massa por dessorção/ionização a laser assistida por matriz (MALDI-TOF-TOF). Foram elas: albumina, alfa enolase, calgranulina B, galectina 7, mioglobina, miosina (cadeia leve 1), miosina (cadeia leve 2) e tropomiosina 2 (beta). Estas proteínas têm sido detectadas com expressão alterada por diferentes autores em carcinomas da cabeça e pescoço e também em outros tumores. Após validação, as proteínas identificadas podem revelar novos biomarcadores de prognóstico e alvos terapêuticos para tumores de cabeça e pescoço. / Abstract: Head and neck squamous cell carcinoma is an aggressive cancer. It is closely related to the practice of tobacco smoking and alcohol abuse. The high recurrence, heterogeneous biological aggressiveness and low survival rates of this group of cancer require our efforts to understand the pathogenesis of the disease and to develop better therapeutic strategies. In the present study, we investigated whether proteome analysis can identify differences in protein expression between low and high stage head and neck carcinomas. To reach this aim we optimized protocols for protein extraction and established two-dimensional electrophoresis in the laboratory. Proteome profiling patterns were analyzed in eight oral and two oropharyngeal tumor samples (eight from carcinomas presenting lymph node metastasis and two from carcinomas with no regional metastasis) and in 17 apparently normal surgical margins. Qualitative and quantitative variations in both groups were consistent and eight proteins were identified by matrix assisted laser desorption/ionization - time of flight - time of flight (MALDI-TOFTOF) mass spectrometry. These proteins were: albumin, alpha enolase, calgranulin B, galectin 7, myoglobin, myosin (light chain 1), myosin (light chain 2) and tropomyosin beta chain. These proteins have shown to be with altered expression by different studies in head and neck cancers and also in other tumors. After validation, the proteins identified here could be novel biomarkers for prognosis and rational targets for head and neck tumors. / Orientador: Eloiza Helena Tajara da Silva / Coorientador: Mario Sergio Palma / Banca: Eny Maria Goloni Bertollo / Banca: Gustavo Orlando Bonilla Rodriguez / Mestre

Topoisomerases são enzimas nucleares que participam na regulação da estrutura do DNA nas células eucarióticas. A topoisomerase III é o mais novo membro da família das topoisomerases. Seu papel no desenvolvimento dos tumores mamários ainda necessita ser investigado. O objetivo do presente estudo foi avaliar a imunoexpressão da topoisomerase III nos carcinomas mamários, e comparar sua expressão com dados clinicopatológicos e marcadores imunohistoquímicos clássicos de importância prognóstica nos carcinomas mamários. Utilizando-se tissue microarrays contendo 171 casos de carcinomas ductais mamários primários, foi analisada a expressão imunohistoquímica de topoisomerase III, receptor de estrógeno, receptor de progesterona, HER-2, Ki67, p53 e BRCA-1. Positividade para topoisomerase III foi encontrada em 33,9% dos casos, e sua expressão relacionou-se com metástases à distância (p=0.036) e óbito (p=0.006). Negatividade para topoisomerase III relacionou-se com negatividade para HER=2 (p<0.001), p53 (p<0.001) e BRCA-1 (p=0.001), e com baixa expressão de Ki-67 (p<0.001). Na Análise de Riscos Múltiplos de Cox, a expressão de topoisomerase III foi um significante preditor de sobrevida [razão de risco 3.006 (intervalo de confiança a 95%: 1.582-5.715); p=0.001]. Concluindo, a topoisomerase III pode ser útil na avaliação do prognóstico de pacientes com câncer de mama, além de ser um fator independente de predição da sobrevida. / Topoisomerases are ubiquitous nuclear enzymes that regulate DNA structure in eukaryotic cells. The role of topoisomerase III, the newest member of the topoisomerase family, in the clinical outcome of breast cancer is still poorly understood. This study aims to investigate the immunoexpression of topoisomerase III in breast cancer and its relationships with clinicopathological features and immunohistochemical markers of prognostic significance in breast pathology. Using tissue microarrays containing 171 cases of primary invasive breast cancer, we analyzed the immunoexpression of topoisomerase III, estrogen receptor, progesterone receptor, HER-2, Ki67, p53 and BRCA-1. Immunostaining for topoisomerase III was found in 33.9% of breast carcinomas, and immunopositivity was related with distant metastasis (p=0.036) and death (p=0.006). Decreased expression of topoisomerase III was related with negativity with HER-2 (p<0.001), p53 (p<0.001) and BRCA1 (p=0.001) and low expression of Ki67 (p<0.001). In the multivariate analysis, topoisomerase III expression was a significant predictor of survival [hazard ratio 3.006 (95% confidence interval 1.582-5.715); p=0.001]. In conclusion, topoisomerase III expression can be a useful marker in assessing the prognosis of patients with breast cancer and is an independent predictor of survival.

Background: Very recently a gene marker panel that allows the mutational analysis of APC, CTNNB1, B-RAF and K-RAS was conceived. The aim of the present study was to use the 4-gene marker panel covering the Wnt and Ras-Raf-MEK-MAPK signalling pathways to determine the percentage of sporadic colorectal carcinomas (CRC) carrying at least one of the four above-mentioned genes in a mutated form alone and/or in combination with microsatellite instability (MSI) and to compare the sensitivity of the gene marker panel used in this study with that of gene marker panels previously reported in the scientific literature. Methods: CTNNB1 and B-RAF were screened by PCR-single-strand conformation polymorphism analysis and K-RAS gene mutations by restriction fragment length polymorphism analysis. For the mutational analysis of the APC gene mutation cluster region (codons 1243–1567) direct DNA sequencing was performed. The U.S. National Cancer Institute microsatellite panel (BAT25, BAT26, D2S123, D5S346 and D17S250) was used for MSI analysis. Results: It could be shown that about 80% of early stage CRC (UICC stages I and II) and over 90% of CRC in the UICC stage IV carried at least one mutated gene and/or showed MSI. No significant increase in the gene mutation frequencies could be determined when comparing tumours in the UICC stage I with those in UICC stage IV. Conclusions: When compared with previously published gene marker panels the 4-gene marker panel used in the present study shows an excellent performance, allowing to detect genetic alterations in 80–90% of human sporadic CRC samples analyzed.

Se estudiaron 136 carcinomas mamarios de perras y sus linfonódulos satélites. Se evaluaron la proliferación celular (mediante la marcación inmunohistoquímica del antígeno nuclear de proliferación celular) y la actividad angiogénica (mediante la inmunomarcación del receptor para el factor de crecimiento de endotelios vasculares 2 -VEGFR-2- y el recuento de microvasos). Se relacionaron ambos procesos y su repercusión en el estado del linfonódulo. Se estableció la asociación entre estas características y el tipo y grado histológicos, y la presencia de émbolos neoplásicos en los vasos tumorales. Para determinar su significación en el pronóstico, estos parámetros se relacionaron con el estado del linfonódulo (merced a la observación de cortes procesados mediante la técnica histopatológica de rutina y a la marcación inmunohistoquìmica de citoqueratinas) y con la supervivencia de un grupo de pacientes. Los tipos histológicos pudieron clasificarse en dos grupos teniendo en cuenta su comportamiento proliferativo, angiogénico e invasivo: uno constituido por carcinomas complejos, simples tubulares y de células escamosas, y el otro por carcinomas simples papilares, sólidos y anaplásicos y carcinosarcomas. A menor diferenciación histológica correspondieron mayores actividades proliferativa, invasiva y angiogénica. Con respecto a esta última, en neoplasias con mayor expresión del VEGFR-2, la densidad de microvasos y la proliferación fueron mayores. La mayor densidad de vasos favorece la invasión vascular. La presencia de émbolos, el grado histológico, el índice de proliferación, la expresión del VEGFR- 2 y la densidad de microvasos permitieron predecir la capacidad metastásica. El tipo histológico no se relacionó con la supervivencia de manera independiente. Los carcinosarcomas y los carcinomas simples anaplásicos presentaron mayor riesgo de metástasis que los carcinomas simples tubulares, complejos y de células escamosas. La probabilidad de supervivencia a 18 meses fue alta y estuvo influenciada por el estado del linfonódulo y la presencia de émbolos neoplásicos. / One hundred and thirty six canine mammary carcinomas and their satellite lymph nodes were studied. Proliferation and angiogenic activities were evaluated by means of immunohistochemical procedures. For the former, proliferating cell nuclear antigen was labelled. Vascular endothelial growth factor receptor-2 (VEGFR-2) expression and microvessel density were measured to estimate angiogenesis. Both processes were related and their influence on the status of the lymph nodes was investigated. An association was established between these characteristics and the histological type and grade, and the presence of neoplastic cells within tumor vessels. In order to determine their prognostic significance, these parameters were related to the lymph node status (defined after histopathological and immunohistochemical studies with anticytokeratin antibodies) and survival of a group of patients. According to their proliferative, angiogenic, and invasive behavior, histological types could be classified into two groups: one comprising complex, simple tubular, and squamous cell carcinomas, and the other comprising simple papillary, solid, and anaplastic carcinomas, and carcinosarcomas. A lower histological differentiation corresponded to higher proliferative, invasive, and angiogenic activities. Tumors with higher expression of VEGFR-2 exhibited more density of microvessels and higher proliferation rates. Vascular density favored vascular invasion. Metastatic potential could be predicted according to the presence of emboli, histological grade, proliferation index, expression of VEGFR-2, and density of microvessels. Independent correlation between histological type and survival was not found. Carcinosarcomas and simple anaplastic carcinomas presented a higher risk of metastasis than simple tubular, complex, or squamous cell carcinomas.Probability of survival at 18 months was high and was influenced by the status of the lymph node and the presence of neoplastic emboli.

Made available in DSpace on 2014-10-09T12:27:09Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T13:57:22Z (GMT). No. of bitstreams: 0 / Dissertacao (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

AIM & OBJECTIVES: Human papilloma virus (HPV) has been related to cervical infection, however, its part in Head and Neck Squamous Cell Carcinoma (HNSCC) is still debatable and is easy to refute. Suspicion of HPV causation is heightened when carcinomas arise in patients that are young and have never smoked. The present UK based study undertaken at Northampton NHS Trust endeavoured to determine the extent to which HPV is an entity in HNSCC in the UK. Furthermore, the study investigated whether sexual behaviour (as measured by sexual health clinic (SHC) attendance) is linked the acquisition of HPV associated HNSCC in young age groups. HNSCC incidences and sexual trends in the UK were collected from publicly available databases to identify if there were any changes at a national level in sexual behaviours and their influence on HNSCC in young age groups. MATERIALS & METHODS: PCR was used to evaluate the presence of HPV in biopsy samples from of 99 patients diagnosed with HNSCC at Northampton Hospital from 2006 to 2014. Patient demographics on age, sex, smoking, alcohol use and SHC attendance were also collected. All HPV PCR positive biopsies were further genotyped using an ABI 3130xl genetic analyser. Databases in the UK; including GLOBOCAN, NATSAL and PHE were searched for data on HNSCC prevalence, sexual behaviour trends and vaccine uptake. Multinomial regression explored the relationship between HPV positivity and sex, age, smoking, drinking, race and SHC attendance. RESULTS: PCR showed that 25.2% (25/99) of biopsies tested were positive for HPV and were all obtained from white participants. Most specimens (23, 92%) were high-risk (HR) HPV 16 positive with a mean age of 56 for HPV positivity and 72% of the cases 50-60 years old. Smokers were 11% in total (11/99) with most 88.9% participants (88/99) being non-smokers. HPV positivity was strongly linked with non-smoking history (p < 0.001); no alcohol abuse (p < 0.001); male gender (p < 0.001); young age less than 60 years (p < 0.001) and SHC attendance (p < 0.001). A Kruskal-Wallis post hoc test affirmed the impact of age on HPV positivity (p= < 0.05). GLOBOCAN and Cancer Research demonstrated a rising UK HNSCC pattern of over 200% for both sexes from 1975 to 2011. The three NATSAL surveys undertaken in 1990-1991, 1999-2001 and 2010-2012 demonstrated an overall increase in opposite and same sex partners. The UK average of individuals engaging in oral sex was in the younger age groups of between 16 and 54 with at least 70% of males and 63% females of that age engaging in oral sex. Finally, NASTAL 1, 2 and 3 surveys reported 20 vs 15; 25 vs 55; 55 vs 65 of males and females respectively with more than 10 sexual partners to have attended the SHC. The UK immunization take-up was over 90% countrywide. CONCLUSION: Few research studies have been conducted to date on HPV as a cause of HNSCC in the UK. The present research showed 25.2% of HNSCC to be caused by HPV, with the high risk (HR) genotype 16 (the leading cause of cervical cancer) accounting for 92% (23/25) of the cases. These outcomes affirmed the high prevalence of HR-HPV in HNSCC, with a rate of 25.2% similar to those reported previously. Routine HPV testing in those aged below 60 is therefore warranted. Smoking and drinking showed negative correlation; the young age of below 60 and attendance of the SHC for both sexes showed a positive correlation with HPV positive HNSCC. NATSAL data showed increased sexually risky behaviour coupled with attending the SHC in younger ages for both sexes. Increased sexually risky behaviour as shown in NASTAL surveys may be the reason why young age and SHC attendance is positively correlated with HPV HNSCC. The study highlights a conceivable relationship between HPV positive HNSCC in those under 60 years with no smoking history who attended the SHC. Smoking and drinking are known risks for HNSCC in those past 65 years of age; the negative association with HPV HNSCC in the young in the present research revealed smoking and drinking to have reduced association with HPV HNSCC. The reported HR-HPV positive HNSCC in young age groups inform future vaccination strategies and consequently decrease the quantity of HPV HNSCC's.

Made available in DSpace on 2014-06-11T19:25:20Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-02-22Bitstream added on 2014-06-13T20:32:46Z : No. of bitstreams: 1 ribeiro_acp_me_araca.pdf: 376083 bytes, checksum: 848597ab1cea2e95c39e61fb55902c70 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A incidência mundial de câncer em jovens tem aumentado e estudos recentes mostram que o câncer de boca também segue esta tendência. O objetivo deste trabalho foi avaliar e comparar as características clínicas, histopatológicas e imunoistoquímicas entre pacientes jovens, com idade igual ou inferior a 40 anos, e pacientes idosos, com idade igual ou superior a 65 anos, diagnosticados com carcinoma espinocelular em língua. Foram selecionados 19 casos de pacientes jovens e 19 casos de pacientes idosos e coletados dados clínicos dos prontuários. A gradação histológica foi realizada utilizando os critérios de classificação de Bryne et al (1992), na região do fronte tumoral. Também foi analisada a expressão imunoistoquímica das proteínas Bcl-2, Cerb-b2 e Ki-67. Neste estudo foi observado maior número de carcinomas espinocelulares moderadamente e pobremente diferenciados no grupo de pacientes jovens enquanto que no grupo de idosos houve maior prevalência de carcinomas bem diferenciados. Houve também no grupo de pacientes jovens um aumento do infiltrado linfoplasmocitário. A expressão imunoistoquímica das proteínas Bcl-2, Cerb-b2 e Ki-67 não mostrou diferenças significantes no fronte tumoral entre pacientes jovens e idosos. Na amostra estudada, foram detectadas diferenças morfológicas entre o grupo de pacientes jovens e idosos, no entanto, estas diferenças não foram expressas de forma significativa na análise imunoistoquímica. / The worldwide incidence of cancer in young is increasing and recent studies show that the oral cancer also follows this trend. The objective of this study was to evaluate and to compare the clinical, histopathological and immunohistochemical features between young patients, with 40 years old or less, and elderly patients, with 65 years old or a superior age, diagnosed with tongue squamous cell carcinoma. Nineteen cases of young patients and 19 cases of elderly patients were selected and clinical data were collected from medical records. The histological grading was carried out using the criteria of classification of Bryne et al (1992) in the tumoral front region. The immunohistochemical expression of the proteins Bcl-2, Cerb-b2 and Ki-67 was also analyzed. In the present study, the group of young patients presented a higher number of moderately and poor differentiated squamous cell carcinomas whereas the elderly group had a greater prevalence of well differentiated carcinomas. The group of young patients also showed an increase in the lympho-plasmacytic infiltration. The immunohistochemical expression of the proteins Bcl-2, Cerb-b2 and Ki-67 did not show significant differences in the tumoral front region between young and elderly patients. In the studied sample, morphological differences between the group of young and elderly patients were detected, however, these differences were not expressed in in the immunohistochemical analysis.