Introducción Una de las principales razones que limitan la supervivencia final de los pacientes con un carcinoma de cabeza y cuello tras el control de su enfermedad es la aparición de segundas neoplasias. Los criterios para considerar un tumor como una segunda neoplasia fueron definidos por Warren y Gates en 1932. Existen numerosos trabajos que demuestran que los pacientes con un carcinoma de cabeza y cuello cuentan con un riesgo elevado de aparición de segundas neoplasias, y que en la mayoría de ocasiones estas segundas neoplasias se localizan a nivel del tracto aerodigestivo. Una de las conclusiones más interesantes de los estudios longitudinales en pacientes con un tumor índice de cabeza y cuello es que el riesgo de aparición de segundas neoplasias se mantiene elevado de forma constante a lo largo del periodo de seguimiento, con una incidencia anual que varía entre el 2% y el 4%.Sin embargo, no existen estudios que de forma explícita aborden la aparición de nuevos tumores malignos tras la aparición de una segunda neoplasia en los pacientes con carcinomas de cabeza y cuello. Definimos como tercer tumor la aparición de una tercera neoplasia maligna en pacientes con un tumor índice de cabeza y cuello que han sufrido la aparición de una segunda neoplasia, como cuarto tumor la aparición de una cuarta neoplasia maligna en pacientes que han sufrido la aparición de una tercera neoplasia, y así sucesivamente.Nuestro objetivo es evaluar los tumores malignos sucesivos en pacientes tras un tumor índice de cabeza y cuello, estudiando de forma específica la incidencia de aparición de terceros y cuartos tumores, su localización, y la repercusión que tiene su aparición en cuanto a la supervivencia en este grupo de pacientes. Material y MétodosSe recogieron de forma prospectiva desde 1985 hasta 2005 los datos clínicos de 3334 pacientes diagnosticados de carcinomas de cabeza y cuello. En un análisis longitudinal retrospectivo se estudian la incidencia, la supervivencia, la ubicación y la histología de las segundas, terceras y cuartas neoplasias. También se evalúan las modalidades de tratamiento para cada tumor. ResultadosEn el periodo de seguimiento fueron diagnosticadas 716 segundas neoplasias, 110 terceras y 18 cuartas. El riesgo actuarial de aparición de las terceras y cuartas neoplasias (6% y 7%, respectivamente) fue significativamente superior al de los segundos tumores (3,8%).La supervivencia final ajustada disminuyó significativamente después de cada nuevo tumor en cabeza y cuello. La supervivencia actuarial ajustada a 5 años fue del 43% para las segundas neoplasias, del 29% para las terceras y del 11% para las cuartas neoplasias. La utilización de radioterapia como tratamiento del tumor índice redujo significativamente la supervivencia final. Conclusiones El aumento del riesgo de aparición de terceras y cuartas neoplasias se debe a una aceleración de los mecanismos carcinogenéticos después de la segunda neoplasia. La aparición de neoplasias sucesivas produce un empeoramiento gradual en el pronóstico de los pacientes, probablemente relacionado con la progresiva limitación de las opciones de tratamiento. La localización más frecuente de los tumores sucesivos de cabeza y cuello son otra vez en cabeza y cuello y en pulmón.Palabras clave, segundas neoplasias, carcinoma escamoso, neoplasias laringe, neoplasias orofaringe, neoplasias hipofaringe, neoplasias cavidad oral. / IntroductionOne of the main reasons that limit the final survival of head and neck carcinoma patients who achieve control of the disease is the appearance of second neoplasm. The criteria to consider a tumor as a second neoplasm were defined by Warren and Gates in 1932. Numerous studies have probed that head and neck carcinoma patients have an increased risk of appearance of second malignant tumors, and that in most cases these second tumors are located in the aerodigestive tract. The risk of second neoplasm was maintained constant throughout all the follow-up period, with an incidence ranging between 2% and 4% new malignant tumors per year.However, there are not studies approaching the appearance of new malignant tumors in head and neck carcinoma patients after a second neoplasm. A third tumor was defined as any malignant tumor that appeared after a second neoplasm in patients with a head and neck index tumor, a fourth tumor was any malignant tumor that appeared after a third tumor, and so on. The objective of our study was to evaluate the appearance of the successive malignant tumors in patients with a head and neck index tumor, to analyze the incidence of second, third and fourth tumors, their location and effect on survival in this group of patients. Methods: Clinical data of 3334 head and neck cancer patients was prospectively collected from 1985 to 2005. Incidence, survival, location and histology of second, third and successive tumors was evaluated, as well as treatment modalities for every tumor. Results: In the follow up period, 716 second tumors, 110 third tumors and 18 fourth tumors were diagnosed. Actuarial hazard ratio for third and fourth tumors (6% and 7% respectively) was significantly higher than for second tumors (3.8%).Adjusted final survival dropped significantly after every new tumor in the head and neck. Five-year adjusted survival for second was 43%. It decreased to 29% for third tumors and dropped to 11% for fourth tumors.Regarding treatment modalities, index tumor treatment including radiotherapy significantly lowered final survival. Conclusions: The increased risk of third and fourth tumors is probably due to an acceleration of the carcinogenic mechanisms after the second neoplasm. Successive tumors produce a gradual worsening in the prognosis of the patients probably related to the progressive limitation in treatment options. The most frequently location of successive neoplasms are head and neck again and lung.Key words: neoplasms, second primary; carcinoma, squamous cell, laryngeal neoplasms; oropharyngeal neoplasms; hypopharyngeal neoplasms, mouth neoplasms.

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2016-01-29T08:31:16Z No. of bitstreams: 2 Dissertação - Carlos Henrique Pereira - 2014.pdf: 3850945 bytes, checksum: 985b041e7a863070b3fa0562180a40f3 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2016-01-29T08:33:08Z (GMT) No. of bitstreams: 2 Dissertação - Carlos Henrique Pereira - 2014.pdf: 3850945 bytes, checksum: 985b041e7a863070b3fa0562180a40f3 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2016-01-29T08:33:08Z (GMT). No. of bitstreams: 2 Dissertação - Carlos Henrique Pereira - 2014.pdf: 3850945 bytes, checksum: 985b041e7a863070b3fa0562180a40f3 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2014-07-07 / Fundação de Amparo à Pesquisa do Estado de Goiás - FAPEG / Objective: Investigate, on a comparative basis, the expression of the adhesion molecules E-cadherin (E-cad), β-catenin (β-cat) and the proliferation index (Ki-67) at the invasive tumor front (ITF) in Squamous Cell Carcinoma (SCC) and basaloid squamous cell carcinoma (BSCC). Material and Methods: Thirty-five SCC and 16 BSCC cases were evaluated by immunohistochemistry. Clinico-pathological data and survival data were evaluated and compared. Results: There was a low expression of E-cad in the cytoplasmic membrane (p = 0.50) as well as in the nucleus (p = 0.31) for both SCC and BSCC. A high expression of E-cad was seen in the cytoplasm for the SCC group (80%) when compared to the BSCC group (25%) (p<0.01). The expression of β-cat in the cytoplasmic membrane (p = 0.28) and in the cytoplasm (p = 0.44) was low in both SCC and BSCC groups. Both types of carcinoma presented low expressions of β-cat in the nucleus (p = 0.03). The Ki-67 expression was low irrespective of tumor variant. The high expression of E-cad in the cytoplasm was associated with T3/T4 tumors (p = 0.04) in the SCC group and there was no significant association of E-cad, β-cat, Ki-67 with the other clinical variables. In terms of disease-free survival and overall survival, there were no significant differences between SCC and BSCC. Conclusion: The E-cad-β-cat system was found to be dysregulated in both oral SCC and oral BSCC. The Ki-67 cell proliferation index was extremely low in the cases investigated and consequently had no prognostic value. / Objetivo: Investigar comparativamente a expressão das moléculas de adesão E-caderina (E-cad), β-catenina (β-cat) e o índice de proliferação (Ki-67) em Carcinoma Espinocelular (CEC) e Carcinoma escamoso basalóide (CEB). Material e Métodos: Nesse estudo, foram selecionados 35 casos de CEC e 16 casos de CEB e investigados por meio de técnica imuno-histoquímica. A associação das variáveis clinico-patológicas e dados de sobrevida foram avaliados. Resultados: Ambos os grupos tiveram baixa expressão de E-cad em membrana citoplasmática (p=0,50) e núcleo (p=0,31), essa associação não foi estatisticamente significante entre os grupos. Alta expressão de E-cad no citoplasma foi notada no grupo CEC (80%) quando comparado ao grupo CEB (25%), p<0,01. A expressão de β-cat em membrana citoplasmática (p=0,28) e citoplasma (p=0,44) foram baixos em CEC e CEB. Ambos os grupos tiveram baixa expressão de β-cat em núcleo, p=0,03. Não houve diferença estatisticamente significante quanto à expressão de Ki-67 entre os grupos. Alta expressão de E-cad em citoplasma foi associada a tumores T3/T4 (p=0,04) no grupo CEC. Pacientes estilistas apresentaram baixa expressão de β-cat em membrana citoplasmática (p=0,05). Não houve associação entre a expressão de E-cad, β-cat e Ki-67 com as demais variáveis clínicas dos grupos. A sobrevida livre de doença e a sobrevida global não foram estatisticamente significantes na associação entre os grupos CEC e CEB. Conclusão: O sistema E-cad-β-cat encontra-se desregulado tanto nos de CEC quanto nos de CEB de cavidade oral, levando as células epiteliais a perderem o seu fenótipo e promovendo a invasão e progressão tumoral. O índice de Ki-67 foi extremamente baixo não tendo valor prognóstico nos casos avaliados.