Submitted by PPG Odontologia (odontologia-pg@pucrs.br) on 2018-03-09T17:42:57Z No. of bitstreams: 1 RICARDO_LOSEKANN_PAIVA_TES.pdf: 1108231 bytes, checksum: a32ed38f5354b3e7c925afdd81c861e4 (MD5) / Approved for entry into archive by Tatiana Lopes (tatiana.lopes@pucrs.br) on 2018-03-15T13:00:03Z (GMT) No. of bitstreams: 1 RICARDO_LOSEKANN_PAIVA_TES.pdf: 1108231 bytes, checksum: a32ed38f5354b3e7c925afdd81c861e4 (MD5) / Made available in DSpace on 2018-03-15T13:37:24Z (GMT). No. of bitstreams: 1 RICARDO_LOSEKANN_PAIVA_TES.pdf: 1108231 bytes, checksum: a32ed38f5354b3e7c925afdd81c861e4 (MD5) Previous issue date: 2017-11-29 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Oral cytopathology may be used to monitor individuals exposed to risk factor for oral cancer. In this context, the study of field cancerization, a phenomenon involved in the initial stages of oral carcinogenesis, has gained relevance for the establishment of biomarkers that may identify individuals exposed to carcinogens with the greatest risk for developing oral cancer. The first article of this study aimed to compare cytopathological and histopathological characteristics of the clinically normal mucosa adjacent to oral squamous cell carcinoma. The nuclear area of cells obtained by cytological smear of this region was also analyzed and compared to that of individuals without lesions but exposed to smoking and/or alcohol and of patients not exposed to these risk factors. Ninety patients of both sexes over 40 years old were included. In patients with carcinoma, in addition to exfoliative cytology, tissue was obtained from the area adjacent to the tumor for histopathological examination. In smears stained with Papanicolaou, the nuclei of 50 intermediate cells were measured. Both histological sections and cytological smears were classified as low or high-risk. The sensitivity, specificity and accuracy of the cytopathological diagnosis in relation to the histopathological diagnosis, considered the gold standard, were 100, 75 and 75.86%, respectively. The mean nuclear area was significantly lower (p<0.05) in the patients not exposed to the risk factors in relation to the others. The cyto-histopathological comparison of the area adjacent to oral cancer showed good sensitivity, specificity and accuracy. In conclusion, this article demonstrated that nuclear area can be used to detect early cellular changes in the oral mucosa exposed to carcinogens and that mean percentage of nuclei larger than 100 ?m2 is the most indicated method for the assessment of these changes. The second article aimed to assess genetic damage and cell proliferation rate in the field of cancerization, i.e., the clinically normal mucosa adjacent to oral carcinoma. Cytologic smears from the same scrapes used in the first article were stained with silver and with the Feulgen reaction. The mean number of AgNORs/nucleus and micronuclei (MN) was significantly higher (p<0.05) in the Tobacco/Alcohol and Oral Cancer Groups than in the Control Group. Conversely, the mean number of NBUDs was higher in the Control Group compared with the other groups. The number of AgNORs/nucleus and MN/1,000 cells provide evidence of initial oral carcinogenesis at field cancerization areas. Cutoff values for inclusion of individuals exposed to carcinogens in longitudinal monitoring were ? 3.38 AgNORs/nucleus and/or ? 3 MN/1,000 cells. A prospective model including the biomarkers assessed in this study was proposed. / A citopatologia bucal pode ser aplicada como m?todo de monitoramento em indiv?duos expostos a fatores de risco ao c?ncer de boca. O campo de canceriza??o, representando as etapas iniciais da carcinog?nese bucal, torna-se uma ?rea atrativa ao estudo de biomarcadores que poder?o ser utilizados para identificar indiv?duos expostos a carcin?genos com maior risco ao desenvolvimento do c?ncer bucal. O primeiro artigo deste estudo visou comparar as caracter?sticas citopatol?gicas e histopatol?gicas da mucosa clinicamente normal adjacente ao carcinoma espinocelular bucal. Al?m disso, a ?rea nuclear das c?lulas obtidas desta regi?o, por meio de esfrega?o citol?gico, foi mensurada e comparada ? das c?lulas de indiv?duos sem les?o expostos ao fumo e/ou ?lcool e a de pacientes n?o expostos a estes fatores de risco. Foram inclu?dos 90 pacientes de ambos os sexos com idade superior a 40 anos. Nos pacientes com carcinoma, al?m da citologia esfoliativa, foi obtido material para exame histopatol?gico da ?rea adjacente ao tumor. Nos esfrega?os, corados com Papanicolaou, foram mensurados os n?cleos de 50 c?lulas intermedi?rias. Tanto os cortes histol?gicos, quanto os esfrega?os citol?gicos foram classificados em baixo ou alto risco. Ao associar as caracter?sticas citopatol?gicas e histopatol?gicas, verificou-se sensibilidade, especificidade e acur?cia de 100%, 75% e 75,86%, respectivamente. A m?dia da ?rea nuclear foi menor no grupo n?o exposto ao fumo e ao ?lcool, com diferen?a significativa (p<0,05) em rela??o aos demais. A associa??o cito-histopatol?gica da ?rea adjacente ao c?ncer bucal apresentou boa sensibilidade, especificidade e acur?cia. Al?m disso, constatou-se que a ?rea nuclear ? pass?vel de ser utilizada para detectar altera??es celulares precoces na mucosa bucal exposta a carcin?genos, sendo a m?dia percentual de n?cleos com mais de 100 ?m2 o m?todo de avalia??o mais indicado. O segundo artigo objetivou avaliar o dano gen?tico e a velocidade de prolifera??o celular no campo de canceriza??o, ou seja, na mucosa clinicamente normal adjacente ao c?ncer bucal. Os esfrega?os citol?gicos foram corados com a t?cnica das AgNORs e rea??o de Feulgen, utilizando o mesmo raspado citol?gico obtido no primeiro artigo. A m?dia das AgNORs/n?cleo e do micron?cleo (MN) dos grupos fumo/?lcool e carcinoma bucal foi superior, com diferen?a estatisticamente significativa (p<0,05) em rela??o ao grupo controle. Este, por sua vez, obteve m?dia superior de bot?es nucleares (NBUDs) em rela??o aos grupos fumo/?lcool e carcinoma bucal. Ambos os marcadores, n?mero das AgNORs/n?cleo e MN, evidenciaram a fase inicial da carcinog?nese bucal, representada no campo de canceriza??o. Valores iguais ou superiores a 3.38 AgNORs/n?cleo e/ou 3 MN/1000 c?lulas foram identificados como ponto de corte ideal para incluir um indiv?duo exposto a carcin?genos no monitoramento longitudinal. Um modelo prospectivo dos marcadores foi sugerido.