Análise de fatores clínicos, histopatológico e moleculares (p53, Ki67, Bcl2 e PCNA) preditivos de resposta terapêutica à quimioterapia e radioterapia em pacientes com carcinoma espinocelular de laringe e orofaringe

Introducao: tratamento padrao-ouro para pacientes com carcinoma espinocelular (CEC) em estadios clinicos (EC) III e IV e o cirurgico, seguido de radioterapia (RXT). Na preservacao de orgaos, varios esquemas com radioterapia e quimioterapia sao estudados. No entanto, quais pacientes irao melhor responder a esses protocolos e um questionamento ainda sem resposta. Objetivos: avaliar 21 fatores clinicos e um histopatologico, assim como a expressao p53, Bcl2, Ki67 e PCNA como fatores preditivos de resposta a radioterapia e quimioterapia em pacientes com CEC de laringe e orofaringe. Pacientes e Metodo: no periodo de janeiro de 2000 a agosto de 2003, 57 pacientes com CEC da laringe e orofaringe (EC III e IV) foram tratados com RXT e quimioterapia no INCA-MS-RJ. Avaliamos, atraves de analise imunoistoquimica nos blocos de parafina desses pacientes, a expressao da p53, Bcl2, Ki67 e PCNA na mucosa normal, assim como no tumor. Essa expressao foi correlacionada com a resposta ao tratamento, assim como avaliamos a associacao de 22 fatores com essa resposta. Resultados: a toxicidade do tratamento foi alta, levando a 100% dos pacientes a interromperem o tratamento de alguma forma. Resposta completa foi observada em 68,4% dos casos, com sobrevida global de 58,24% e sobrevida livre de doenca de 56,4%. Dos 22 fatores preditivos, apenas a ausencia de hiperalimentacao por sonda nasoenteral (SNE) (p=0,0006), tamanho do tumor (T) (p=0,009) e ausencia de traqueostomia previa (p=0,0002) foram preditivos de boa resposta ao tratamento (analise univariada). A expressao negativa do Bcl2 no tumor, na mucosa e em ambos (p=0,017, 0,04 e 0,028, respectivamente) foram preditivos de boa resposta (analise univariada), com probabilidade, respectivamente, de 3,64; 5,29 e 7,68 vezes maior de resposta quando comparado com a populacao que o expressou. A expressao positiva do Bcl2 foi de 25,5%, do p53 de 55,3%, do Ki67 de 82,6%, do PCNA de 76%. Nenhuma dessas expressoes teve impacto na resposta ao tratamento. Entretanto, ao realizarmos a analise multivariada, apenas a ausencia da traqueostomia previa ao tratamento (p=0,0056) e ausencia de hiperalimentacao por SNE (p=0,002) foram fatores preditores de boa resposta. Conclusoes: das 22 variaveis, apenas a ausencia de hiperalimentacao pela SNE e ausencia de traqueostomia previa foram fatores preditivos de boa resposta ao tratamento. De uma forma isolada (analise univariada), a nao expressao imunoistoquimica do Bcl2 no tumor, na mucosa e em ambos (principalmente) estiveram associados a uma melhor resposta terapeutica. Introduction: the standard treatment for patients with HNSCC stages III and IV is surgical plus radiation therapy (RT). In order to preserve the organs, several schemes using RT and chemotherapy (CT) have been studied. Nevertheless, the patients submitted to this treatment who will better respond to these protocols is not known yet. Objective: to evaluate 22 factors as well as the expressions of proteins p53, Bcl2, Ki67 and PCNA as predictive factors, in response to RT and CT in patients with laryngeal and oropharyngeal SCC. Materials and methods: from January, 2000 to August, 2003, 57 patients with laryngeal and oropharyngeal SCC (Stages III and IV) were treated with RT and CT at INCA-MS-RJ. We analyzed the paraffin blocks of those patients throughout immunohistochemistry study. The positive and negative expressions of p53, Bcl2, Ki67 and PCNA on normal mucosa,as well as in the tumor (and in both of them). The expression was correlated to the response of treatment, as we analyzed the association of 22 clinical factors of patients showing this response. Results: the toxicity of treatment was high, taking 100% of patients to somehow interrupt the treatment. A complete response was observed in 68.4% of the cases, with overall survival rate of 58.24% and disease-free survival rate of 56.4%. Among the 22 predictive factors, only the lack of hypernutrition through nasoenteral tube (p=0.0006), tumor size (T), p=0.009 and the lack of tracheotomy were predictive of a better response to the treatment (univariated analysis). Only the Bcl2 negative expression in the tumor, mucosa and in both (p=0.017, 0.04 and 0.028, respectively) were predictive of a better response (univariated analysis) with support of 3.64; 5.29 and 7.68, respectively, much higher when compared to the population who expressed it. Positive expression of Bcl2 was 25.5%; p53 55.3%; Ki67 82.6%; PCNA 76%. None of those expressions caused any impact to response of treatment. Nevertheless, when a multivariated analysis was made, only the lack of previous tracheotomy to treatment (p=0.0056) and the lack of hypernutrition through NET (p=0.002) were predictive factors for a better result. Conclusions: among 22 predictive factors, only the lack of hypernutrition through SNE and the lack of previous tracheotomy were predictive factors for better results. Throughout an univariated analysis the non-immunohistochemistry expression of Bcl2 in the tumor, on mucosa and in both (mainly), had a good impact in therapeutic response.