Nuclear markers (star volume, mitotic index, AgNOR and Ki-67) of the primary tumor and its metastasis in non-small cell lung carcinomas.

Although tumor growth is controlled by growth rate and cell cycle, it is also likely that the proliferative activity of tumor cells can influence the growth rate of the primary cancer and account for their aggressiveness. Variations in growth rate, cell cycle control and proliferative activity could, in part, explain differences in invasive and metastatic properties among non-small cell lung carcinomas (NSLC). The purpose of this report is to: (1) evaluate growth rate by using growth- and cell cycle-regulating markers (mitotic count, nuclear star volume, AgNOR, and Ki-67) as reflections of growth rate and (2) compare the indices of primary NSLC with the indices of their metastasis in a series of patients with advanced disease. Thirty-three patients with non-small cell lung cancer and hematogenous metastases were retrospectively studied by histochemical, immunohistochemical, and morphometrical investigations. Clinical variables were examined for differences in the frequency of histological subtypes, nuclear star volume, mitotic index, AgNOR area, and Ki-67 immunohistochemistry indices of expression in subgroups of patients stratified by primary tumor and hematogenic metastasis. The impact of these factors on overall follow-up was analyzed. In the samples available in this study, consisting of primary-met paired tumors, which are unique and rarely available for studies of lung cancer, we found that nuclear star volume and mitotic index in metastatic tumors were significantly higher than in the primary tumors. Although there was no significant difference between the Ki-67 index of metastatic and primary tumors, the Ki-67 index in metastatic brain tumors was significantly higher than in the corresponding primary tumors. Examination of Kaplan-Meier survival curves demonstrated that patients with metastatic tumors showing AgNOR area higher than 10.82 microm2 and nuclear star volume lower than 559.50 microm3 had approximately the same odds ratio (log rank of 4.16 and 3.25, p = 0.04 and 0.01, respectively) for survival with a median survival time equal to 17 months for both groups. Analysis of the remaining marker correlation had no impact on survival. We conclude that these results offer future possibilities for more complex studies, including the results of additional immunohistochemical analysis using molecular markers that are known to be important in regulating cell proliferation, e.g., cyclin D1, p27, and cyclin E. These would influence clinical decisions or different therapeutic approaches in advanced stage disease of non-small cell lung cancer.

Requisitos mínimos para o laudo de anatomia patológica em câncer de pulmão: justificativas na patogênese / Minimum requirements for the anatomopathological report in lung cancer: justifications in the pathogenesis

O pulmão é uma fonte de grande número de espécimens citológicos e histológicos. Destes espécimens o patologista deverá emitir um diagnóstico, tendo, dessa forma, importante papel no estabelecimento do estadiamento clínico e patológico. A prioridade do patologista na avaliação de um tumor pulmonar, para fazer um diagnóstico histológico específico, reside na avaliação do espécimen histológico; contudo, pode ser acompanhada de preparados citológicos. Aqui pode fazer-se necessária a suplementação por técnicas histoquímicas e imunoistoquímicas. Se houver adequadas condições de fixação do tecido, técnicas especiais como microscopia eletrônica, imunoistoquímica em material congelado, citogenética e estudos moleculares poderão ser realizados. Exceção será feita se o material for muito pequeno, quando então deverá ser totalmente submetido à técnica de rotina; neste caso, se o diagnóstico não puder ser elaborado, biópsias subseqüentes poderão ser prospectivamente obtidas e direcionadas para a técnica especial de estudo. Este é o caso freqüentemente encontrado nos linfomas malignos, nos quais os espécimens de biópsia poderão ser muito pequenos e insuficientes para o diagnóstico definitivo sem imunofenotipagem. O estadiamento patológico de tumor primário de pulmão será alcançado quando houver adequado estudo macro e microscópico. Os procedimentos descritos a seguir poderão ser aplicados para ressecções por segmentectomia, lobectomia, pneumectomia, ressecções em bloco, traquéia ou brônquios