Alterações no padrão normal de metilação do DNA têm sido caracterizadas como um importante mecanismo na gênese de neoplasias. Esta modificação do DNA é denominada de epigenética uma vez que altera o padrão de expressão das células sem alterar a seqüência do DNA. No câncer, as alterações epigenéticas observadas consistem na hipermetilação das ilhas CpG nos promotores dos genes acompanhada de uma hipometilação global dos dinucleotídeos CpG dispersos pelo genoma. Este evento mostra geralmente ser câncer-específico, ou seja, alguns genes que são metilados em um tipo de câncer, não o são na maioria dos outros tipos. O objetivo deste projeto foi identificar, através da construção de bibliotecas subtrativas de RaSH, genes silenciados por metilação nas linhagens de câncer de cabeça e pescoço FaDu, UM-SCC-14A, UM-SCC-17A e UM-SCC-38 e que possuem expressão induzida após o tratamento com o agente demetilante 5-aza-2-deoxicitidina. Uma vez que a metilação leva a diminuição gradual da expressão gênica, o método RT-PCR semi-quantitativo foi utilizado para validação da expressão diferencial dos genes candidatos PLAU, CD82, RBBP4, AOF2, TMSB10, HSPA5 e LAMC2 nas linhagens não tratadas e tratadas com o agente demetilante 5-aza-2-deoxicitidina. Para todos os genes candidatos foi observado aumento na expressão gênica após o tratamento em pelo menos uma das quatro linhagens. Na linhagem UM-SCC-14 A, os genes CD82, RBBP4, AOF2, HSPA5 e LAMC2 mostraram aumento na expressão após o tratamento com o agente demetilante, sendo que o gene LAMC2 também mostrou esse aumento de expressão na linhagem UM-SCC-17A. Na linhagem UM-SCC-38A todos os genes mostraram aumento de expressão após o tratamento. Embora novos estudos sobre a metilação da região promotora dos genes selecionados sejam necessários, aumentam as evidências de que os genes selecionados sejam regulados pelo mecanismo de metilação e que estejam metilados nas linhagens estudadas. / Abnormalities on the normal pattern of DNA methylation have been caracterized as an important mechanism on carcinogenesis. This modification is called epigenetic and can be defined as a heritable change in gene expression that is not accompanied by changes in DNA sequence. The epigenetic alterations observed on cancer include hypermethylation of selected CpG island gene promoters and simultaneous global hypomethylation. The aim of this project was to identify, by rapid subtraction hybridization, genes silenced by methylation on head and neck cancer lineages with alterations on gene expression after the treatment with 5-aza-2-deoxycytidine. The cancer lineages we used for our experiments were: FaDu, UM-SCC-14A, UM-SCC-17A e UM-SCC-387A and seven genes (PLAU, CD82, RBBP4, AOF2, TMSB10, HSPA5 and LAMC2) were analysed by semiquantitative RT-PCR and for all of them an increaseament of gene expression was observed. For the UM-SCC-14A lineage, the genes CD82, RBBP4, AOF2, HSPA5 and LAMC2 were upregulated after the treatment with demethylating agent as well as LAMC2 was uperegulated on UM-SCC-17A. For the UM-SCC-38A lineage all the genes showed increased expression after the treatmente with -aza-2-deoxycytidine. Our work is another evidence that some genes may be regulated by methylation during carcinogenesis.

Alterações no padrão normal de metilação do DNA têm sido caracterizadas como um importante mecanismo na gênese de neoplasias. Esta modificação do DNA é denominada de epigenética uma vez que altera o padrão de expressão das células sem alterar a seqüência do DNA. No câncer, as alterações epigenéticas observadas consistem na hipermetilação das ilhas CpG nos promotores dos genes acompanhada de uma hipometilação global dos dinucleotídeos CpG dispersos pelo genoma. Este evento mostra geralmente ser câncer-específico, ou seja, alguns genes que são metilados em um tipo de câncer, não o são na maioria dos outros tipos. O objetivo deste projeto foi identificar, através da construção de bibliotecas subtrativas de RaSH, genes silenciados por metilação nas linhagens de câncer de cabeça e pescoço FaDu, UM-SCC-14A, UM-SCC-17A e UM-SCC-38 e que possuem expressão induzida após o tratamento com o agente demetilante 5-aza-2-deoxicitidina. Uma vez que a metilação leva a diminuição gradual da expressão gênica, o método RT-PCR semi-quantitativo foi utilizado para validação da expressão diferencial dos genes candidatos PLAU, CD82, RBBP4, AOF2, TMSB10, HSPA5 e LAMC2 nas linhagens não tratadas e tratadas com o agente demetilante 5-aza-2-deoxicitidina. Para todos os genes candidatos foi observado aumento na expressão gênica após o tratamento em pelo menos uma das quatro linhagens. Na linhagem UM-SCC-14 A, os genes CD82, RBBP4, AOF2, HSPA5 e LAMC2 mostraram aumento na expressão após o tratamento com o agente demetilante, sendo que o gene LAMC2 também mostrou esse aumento de expressão na linhagem UM-SCC-17A. Na linhagem UM-SCC-38A todos os genes mostraram aumento de expressão após o tratamento. Embora novos estudos sobre a metilação da região promotora dos genes selecionados sejam necessários, aumentam as evidências de que os genes selecionados sejam regulados pelo mecanismo de metilação e que estejam metilados nas linhagens estudadas. / Abnormalities on the normal pattern of DNA methylation have been caracterized as an important mechanism on carcinogenesis. This modification is called epigenetic and can be defined as a heritable change in gene expression that is not accompanied by changes in DNA sequence. The epigenetic alterations observed on cancer include hypermethylation of selected CpG island gene promoters and simultaneous global hypomethylation. The aim of this project was to identify, by rapid subtraction hybridization, genes silenced by methylation on head and neck cancer lineages with alterations on gene expression after the treatment with 5-aza-2-deoxycytidine. The cancer lineages we used for our experiments were: FaDu, UM-SCC-14A, UM-SCC-17A e UM-SCC-387A and seven genes (PLAU, CD82, RBBP4, AOF2, TMSB10, HSPA5 and LAMC2) were analysed by semiquantitative RT-PCR and for all of them an increaseament of gene expression was observed. For the UM-SCC-14A lineage, the genes CD82, RBBP4, AOF2, HSPA5 and LAMC2 were upregulated after the treatment with demethylating agent as well as LAMC2 was uperegulated on UM-SCC-17A. For the UM-SCC-38A lineage all the genes showed increased expression after the treatmente with -aza-2-deoxycytidine. Our work is another evidence that some genes may be regulated by methylation during carcinogenesis.

O câncer tem sido considerado uma doença de países desenvolvidos e em desenvolvimento, sendo que a maior parte do ônus global do câncer é observada nos países em desenvolvimento, convertendo-se em um evidente problema de saúde pública mundial. Devido a sua alta incidência, prevalência e mortalidade, o câncer de cabeça e pescoço, é considerado um dos principais tumores no Brasil e no mundo, sendo o câncer bucal um dos tipos mais incidentes, correspondendo a 10% de todos os tumores malignos, com aproximadamente 390.000 novos casos a cada ano. As taxas de incidências variam conforme as regiões do Brasil, tendo a região sudeste e sul as maiores taxas de incidência do mundo, sendo a região sudeste responsável por 42% do número total de casos o Brasil. Os fatores de risco são tabagismo, alcoolismo, hábitos alimentares, radiação solar, vírus, idade, sexo, irritação mecânica/química, nível socioeconômico além de fatores genéticos. Embasados neste contexto, o objetivo deste estudo foi verificar a prevalência, perfil clínico e epidemiológico do câncer bucal e de cabeça e pescoço de pacientes registrados no Hospital Estadual de Bauru/SP, um hospital público no interior do estado de São Paulo, através de revisão de prontuários no período de junho de 2008 à janeiro de 2011, apresentando dados como: localidade, idade, sexo, etnia, prevalência da região anatômica, sintomas, tipo de encaminhamento, tipo histológico, estadiamento, fatores de risco, tratamento, índice de óbito, sobrevida e se o paciente tinha familiares. Foram analisados 177 prontuários, sendo 54% (96) dos pacientes provenientes de Bauru/Sp. Do total de pacientes, 156(88,14%) eram do gênero masculino e 21 (11,86%) do gênero feminino, com médias de idade respectivamente de 60,2 anos e 54,0 anos. Houve predomínio de indivíduos brancos com 141 (80,20%) casos. As regiões anatômicas mais acometidas foram a hipofaringe com 34(19,20%) casos e a língua com 30(16,95%) casos. Os sintomas relatados foram emagrecimento, dor, disfagia, disfonia, rouquidão, otalgia, hemorragia oral, trismo, xerostomia, necrose e odor fétido, os quais ocorreram associados ou isolados. Apenas 1 (0,06) paciente foi encaminhado pelo dentista, e quanto a diferenciação histológica, houve predomínio de carcinoma espinocelular com 98,30% dos pacientes. Foi constatado o câncer em grau III e IV (avançado) em 114 (64,40%) pacientes, com metástase em 45,20% (80) dos casos totais. Ficou evidenciado o consumo associado do fumo e álcool em 76 (42,94%) dos prontuários. Os tratamentos predominantes foram a quimioterapia isolada ou associada à radioterapia, considerada predominante devido ao avanço da doença. Do número total de casos, 83 (46,89%) pacientes foram à óbito com sobrevida média de 1,05 anos. Fundamentados em nossos resultados, ao aumento da expectativa de vida, do envelhecimento da população e da elevada magnitude do problema, sugerimos reavaliar medidas de promoção e prevenção de saúde a população e profissionais de saúde sobre o autoexame bucal e redução do consumo de fatores de risco. Programas educacionais para populações de alto risco com auxílio das Políticas Públicas de Saúde do município em meios de comunicação acessíveis as classes menos favorecidas, podem ser fundamentais para atenuar o número de casos novos de câncer. / Cancer has been considered a disease of developed and developing countries, because of the greater part of the global cancer burden be observed in developing countries, becoming evident at a public health problem worldwide. Because of its high incidence, prevalence and mortality, cancer of the head and neck, is considered one of the main tumors in Brazil and worldwide, and oral cancer one of the most insidious types, corresponding to 10% of all malignant tumors, with approximately 390,000 new cases each year. The incidence rates vary according to region of Brazil, with the southeastern and southern highest incidence rates in the world, being the southeast accounted for 42% of the total number of cases in Brazil. The risk factors are smoking, alcohol, diet, radiation, viruses, age, gender, mechanical irritation / chemical, socioeconomic status as well as genetic factors. Grounded in this context, the aim of this study was to determine the prevalence, clinical and epidemiological profile of oral cancer and head and neck patients enrolled in the State Hospital of Bauru / SP, a public hospital in the state of São Paulo, by reviewing medical records from June 2008 to January 2011, presenting data such as location, age, gender, ethnicity, prevalence of anatomic, symptoms, type of referral, histological type, staging, risk factors, treatment, mortality was , survival and whether the patient had family. 177 records were analyzed, 54% (96) of the patients from Bauru / Sp. Of all patients, 156 (88.14%) were male and 21 (11.86%) females, with a mean age of 60.2 years respectively and 54.0 years. There was a predominance of white individuals with 141 (80.20%) cases. The anatomical regions most affected were the hypopharynx with 34 (19.20%) cases and the tongue with 30 (16.95%) cases. Reported symptoms were weight loss, pain, dysphagia, dysphonia, hoarseness, earache, oral bleeding, trismus, xerostomia, necrosis and foul odor, which occurred isolated or associated. Only 1 (0.06) patient was referred by the dentist, and the histologic differentiation predominated squamous cell carcinoma with 98.30% of the patients. Cancer was found in grade III and IV (advanced) in 114 (64.40%) patients with metastasis in 80 (45.20%) of the total cases. Evidenced the associated consumption of tobacco and alcohol in 76 (42.94%) of the charts. The treatments were predominant chemotherapy alone or combined with radiotherapy, considered predominantly due to disease progression. Of the total cases, 83 (46.89%) patients died at the median survival of 1.05 years. Based on our results, the increase in life expectancy, an aging population and the high magnitude of the problem, we suggest reevaluate measures to promote prevention and population health and health professionals about oral self-examination and reduction of risk factors . Educational programs for high-risk populations with the aid of Public Health Policies of the municipality in media accessible to the lower classes, can be critical to mitigate the number of new cancer cases.

O câncer tem sido considerado uma doença de países desenvolvidos e em desenvolvimento, sendo que a maior parte do ônus global do câncer é observada nos países em desenvolvimento, convertendo-se em um evidente problema de saúde pública mundial. Devido a sua alta incidência, prevalência e mortalidade, o câncer de cabeça e pescoço, é considerado um dos principais tumores no Brasil e no mundo, sendo o câncer bucal um dos tipos mais incidentes, correspondendo a 10% de todos os tumores malignos, com aproximadamente 390.000 novos casos a cada ano. As taxas de incidências variam conforme as regiões do Brasil, tendo a região sudeste e sul as maiores taxas de incidência do mundo, sendo a região sudeste responsável por 42% do número total de casos o Brasil. Os fatores de risco são tabagismo, alcoolismo, hábitos alimentares, radiação solar, vírus, idade, sexo, irritação mecânica/química, nível socioeconômico além de fatores genéticos. Embasados neste contexto, o objetivo deste estudo foi verificar a prevalência, perfil clínico e epidemiológico do câncer bucal e de cabeça e pescoço de pacientes registrados no Hospital Estadual de Bauru/SP, um hospital público no interior do estado de São Paulo, através de revisão de prontuários no período de junho de 2008 à janeiro de 2011, apresentando dados como: localidade, idade, sexo, etnia, prevalência da região anatômica, sintomas, tipo de encaminhamento, tipo histológico, estadiamento, fatores de risco, tratamento, índice de óbito, sobrevida e se o paciente tinha familiares. Foram analisados 177 prontuários, sendo 54% (96) dos pacientes provenientes de Bauru/Sp. Do total de pacientes, 156(88,14%) eram do gênero masculino e 21 (11,86%) do gênero feminino, com médias de idade respectivamente de 60,2 anos e 54,0 anos. Houve predomínio de indivíduos brancos com 141 (80,20%) casos. As regiões anatômicas mais acometidas foram a hipofaringe com 34(19,20%) casos e a língua com 30(16,95%) casos. Os sintomas relatados foram emagrecimento, dor, disfagia, disfonia, rouquidão, otalgia, hemorragia oral, trismo, xerostomia, necrose e odor fétido, os quais ocorreram associados ou isolados. Apenas 1 (0,06) paciente foi encaminhado pelo dentista, e quanto a diferenciação histológica, houve predomínio de carcinoma espinocelular com 98,30% dos pacientes. Foi constatado o câncer em grau III e IV (avançado) em 114 (64,40%) pacientes, com metástase em 45,20% (80) dos casos totais. Ficou evidenciado o consumo associado do fumo e álcool em 76 (42,94%) dos prontuários. Os tratamentos predominantes foram a quimioterapia isolada ou associada à radioterapia, considerada predominante devido ao avanço da doença. Do número total de casos, 83 (46,89%) pacientes foram à óbito com sobrevida média de 1,05 anos. Fundamentados em nossos resultados, ao aumento da expectativa de vida, do envelhecimento da população e da elevada magnitude do problema, sugerimos reavaliar medidas de promoção e prevenção de saúde a população e profissionais de saúde sobre o autoexame bucal e redução do consumo de fatores de risco. Programas educacionais para populações de alto risco com auxílio das Políticas Públicas de Saúde do município em meios de comunicação acessíveis as classes menos favorecidas, podem ser fundamentais para atenuar o número de casos novos de câncer. / Cancer has been considered a disease of developed and developing countries, because of the greater part of the global cancer burden be observed in developing countries, becoming evident at a public health problem worldwide. Because of its high incidence, prevalence and mortality, cancer of the head and neck, is considered one of the main tumors in Brazil and worldwide, and oral cancer one of the most insidious types, corresponding to 10% of all malignant tumors, with approximately 390,000 new cases each year. The incidence rates vary according to region of Brazil, with the southeastern and southern highest incidence rates in the world, being the southeast accounted for 42% of the total number of cases in Brazil. The risk factors are smoking, alcohol, diet, radiation, viruses, age, gender, mechanical irritation / chemical, socioeconomic status as well as genetic factors. Grounded in this context, the aim of this study was to determine the prevalence, clinical and epidemiological profile of oral cancer and head and neck patients enrolled in the State Hospital of Bauru / SP, a public hospital in the state of São Paulo, by reviewing medical records from June 2008 to January 2011, presenting data such as location, age, gender, ethnicity, prevalence of anatomic, symptoms, type of referral, histological type, staging, risk factors, treatment, mortality was , survival and whether the patient had family. 177 records were analyzed, 54% (96) of the patients from Bauru / Sp. Of all patients, 156 (88.14%) were male and 21 (11.86%) females, with a mean age of 60.2 years respectively and 54.0 years. There was a predominance of white individuals with 141 (80.20%) cases. The anatomical regions most affected were the hypopharynx with 34 (19.20%) cases and the tongue with 30 (16.95%) cases. Reported symptoms were weight loss, pain, dysphagia, dysphonia, hoarseness, earache, oral bleeding, trismus, xerostomia, necrosis and foul odor, which occurred isolated or associated. Only 1 (0.06) patient was referred by the dentist, and the histologic differentiation predominated squamous cell carcinoma with 98.30% of the patients. Cancer was found in grade III and IV (advanced) in 114 (64.40%) patients with metastasis in 80 (45.20%) of the total cases. Evidenced the associated consumption of tobacco and alcohol in 76 (42.94%) of the charts. The treatments were predominant chemotherapy alone or combined with radiotherapy, considered predominantly due to disease progression. Of the total cases, 83 (46.89%) patients died at the median survival of 1.05 years. Based on our results, the increase in life expectancy, an aging population and the high magnitude of the problem, we suggest reevaluate measures to promote prevention and population health and health professionals about oral self-examination and reduction of risk factors . Educational programs for high-risk populations with the aid of Public Health Policies of the municipality in media accessible to the lower classes, can be critical to mitigate the number of new cancer cases.

Abstract Free flap surgery (FFS) is used for the reconstruction of head and neck defects after tumor resection. Compared to many other cancers requiring operative care, postoperative complications are frequent and the long-term outcome is poor in this patient group. The impact of postoperative complications on outcome, quality of life (QOL) and causes of death has not been well studied. The aim of this thesis was to study the factors associated with postoperative complications after FFS for cancer of the head and neck, as well as the impact of complications on QOL and long-term outcomes. The thesis includes one prospective and three retrospective studies. The study population was 146 head and neck patients undergoing FFS in Oulu University Hospital from 2008 to 2016. The impact of goal-directed fluid management using SVV (stroke volume variation) analysis on postoperative outcome was evaluated retrospectively. It led to a significant reduction in intraoperative fluid administration (6070 ml vs. 8185 ml) and length of stay (LOS) in hospital (11.5 vs. 14.0 days) but had no impact on the rate of postoperative complications. Postoperative complications were recorded in 60% of the patients and were related to alcohol abuse, complicated intraoperative course and fibular flap surgery. The patients with late complications (occurring after the fourth postoperative day) had higher mortality compared to those without. The QOL of 53 patients undergoing operations during 2013-2016 was evaluated using four questionnaires. Patients with medical complications (n=12, 22.6%) had significantly lower QOL in most domains of RAND-36 but QOL for those without complications was comparable to the general population. A total of 62/146 patients (42.5%) died by the end of 2016, and in 72.6% of cases the cause of death was the primary disease. In multivariate analysis male gender, low BMI, ASA above 2 and late medical complications were indicative for long-term mortality. In conclusion, postoperative complications have an impact on outcome after FFS for cancer of the head and neck in terms of QOL and long-term mortality. Patient-related factors were associated with unfavorable outcomes when intraoperative factors did not have as significant a role. Prevention of medical complications and adequate patient selection are essential when aiming to improve outcome after FFS. / Tiivistelmä Mikrovaskulaarikielekkeitä käytetään korjaamaan kasvaimen poiston vuoksi syntyneitä kudospuutoksia pään ja kaulan alueen syöpäpotilailla. Näihin toimenpiteisiin liittyy merkittävä komplikaatioriski ja myös itse syövän pitkäaikaisennuste on huono. Komplikaatioiden vaikutusta toipumisvaiheen elämänlaatuun ja kuolleisuuteen ei ole tutkittu. Tämän väitöskirjatyön tavoitteena oli selvittää tekijöitä, jotka liittyvät leikkauksen jälkeisiin komplikaatioihin, ja niiden merkitystä potilaiden elämänlaatuun ja pitkäaikaisennusteeseen. Tutkimuskokonaisuus koostuu kolmesta retrospektiivisestä tutkimuksesta ja yhdestä prospektiivisesta haastattelututkimuksesta. Tutkimukseen kuului 146 vuosina 2008–2016 Oulun yliopistollisessa sairaalassa leikattua pään ja kaulan alueen syöpäpotilasta. Tutkimuksessa selvitettiin tavoiteohjatun nestehoidon vaikutusta välittömään toipumisvaiheeseen, mutta tällä ei todettu olevan vaikutusta komplikaatioiden ilmaantumiseen. Sen sijaan potilaiden saama nestemäärä väheni merkitsevästi (6070 ml vs. 8185 ml) ja sairaalahoitojakson pituus lyheni (11,5 päivää vs. 14 päivää). Komplikaatioita todettiin 60 % leikkauksista ja useimmin komplikaation sai potilas, jolla oli alkoholin liikakäyttöä, ongelmia toimenpiteen aikana ja luullinen siirre. Neljännen leikkauksen jälkeisen päivän jälkeen ilmenneisiin komplikaatioihin liittyi korkeampi pitkäaikaiskuolleisuus. Elämänlaatu arvioitiin 53 potilaalta, jotka oli leikattu vuosina 2013–2016. Ei-kirurgisia komplikaatioita esiintyi 12 potilaalla ja heidän raportoimansa elämänlaatu oli merkitsevästi alentunut verrattuna muihin potilaisiin. Ilman komplikaatioita toipuneiden elämänlaatu oli verrattavissa väestöarvoihin. 42,5 % leikatuista potilaista oli kuollut vuoden 2016 loppuun mennessä ja 72,6 % heistä kuolema johtui hoidetusta syövästä. Monimuuttujamallissa pitkäaikaiskuolleisuuden riskitekijöitä olivat miessukupuoli, matala BMI, ASA-luokka yli 2 sekä todetut ei-kirurgiset komplikaatiot. Yhteenvetona voidaan todeta, että komplikaatioilla on merkitystä toipumisvaiheen elämänlaatuun ja pitkäaikaiskuolleisuuteen tässä potilasryhmässä. Potilaslähtöiset tekijät vaikuttavat merkittävästi komplikaatioiden ilmaantumiseen ja myös huonoon ennusteeseen. Ei-kirurgisten komplikaatioiden estäminen kuten myös oikea potilasvalinta ovat keskeisessä asemassa, kun tämän potilasryhmän hoidon tuloksia halutaan parantaa.

No description available.

Deregulation of gene expression caused by genetic or epigenetic changes plays an important role in pathogenesis of cancer. The thesis is a commented collection of ten publications dealing with the molecular biology of tumours. The author has significantly contributed to all of them. All the articles contained in the thesis are linked to the topic of assessment of molecules involved in gene expression regulation (microRNAs) or DNA alterations that affect gene expression (promoter methylation, presence of a fusion gene). MicroRNAs are short single-stranded RNA molecules involved in posttranscriptional regulation of gene expression by triggering mRNA degradation or inhibiting translation. It is a basic mechanism with an impact on all cellular processes including the pathogenesis of various diseases. MicroRNAs can either act as oncogenes by decreasing the expression of tumour-suppressor genes or as tumour-suppressor genes by decreasing the expression of oncogenes. However, the network of microRNA - RNA interactions is much more complex. Our published results that are part of this thesis are focused on colorectal carcinoma (CRC), prostate cancer, head and neck squamous cell carcinoma (HNSCC), gastric cancer and non-small cell lung cancer (NSCLC). In patients with CRC, we demonstrated the prognostic...

Deregulation of gene expression caused by genetic or epigenetic changes plays an important role in pathogenesis of cancer. The thesis is a commented collection of ten publications dealing with the molecular biology of tumours. The author has significantly contributed to all of them. All the articles contained in the thesis are linked to the topic of assessment of molecules involved in gene expression regulation (microRNAs) or DNA alterations that affect gene expression (promoter methylation, presence of a fusion gene). MicroRNAs are short single-stranded RNA molecules involved in posttranscriptional regulation of gene expression by triggering mRNA degradation or inhibiting translation. It is a basic mechanism with an impact on all cellular processes including the pathogenesis of various diseases. MicroRNAs can either act as oncogenes by decreasing the expression of tumour-suppressor genes or as tumour-suppressor genes by decreasing the expression of oncogenes. However, the network of microRNA - RNA interactions is much more complex. Our published results that are part of this thesis are focused on colorectal carcinoma (CRC), prostate cancer, head and neck squamous cell carcinoma (HNSCC), gastric cancer and non-small cell lung cancer (NSCLC). In patients with CRC, we demonstrated the prognostic...