1- Houve associação da imuno-expressão da proteína Bad com pacientes com idade maior de 50 anos nos tecidos de mucosa gástrica não tumoral. .
2- Houve associação da proteína p53 com o tamanho do tumor (>3 cm). 3- Houve associação da proteína Ki-67 com a intensidade de inflamação. 4- Houve associação da expressão das proteínas Bax, Bad e Ki-67 com o adenocarcinoma de tipo intestinal.
5- As proteínas pró-apoptóticas da família Bcl-2 mostraram correlação positiva entre si, tanto no tumor quanto na mucosa não tumoral.
6- Houve correlação positiva das proteínas pró-apoptóticas da família Bcl-2 com a proteína anti-apoptótica Bcl-xl nos adenocarcinomas.
7- As proteínas Bcl-xl, Bak, Bad, p53 e ki-67 apresentaram diferenças estatisticamente significantes entre a imunoexpressão no tumor e na mucosa não tumoral;
8. Nos adenocarcinomas as proteínas Bcl-xl, Bax, Bad e p53 correlacionaram-se positivamente com a expressão de Ki-67.
9. Os adenocarcinomas exibiram maior imuno-expressão da proteína Ki-67 e de caspase 3 clivada.
6 CONCLUSÕES
1- No câncer gástrico a expressão das proteínas da família Bcl-2 (Bcl-2, Bcl-xl, Bax, Bak e Bad) e da proteína p53 está desregulada, favorecendo o desequilíbrio entre proliferação celular e apoptose, permitindo o crescimento descontrolado de células neoplásicas.
2- A expressão destas proteínas não está influenciando a sobrevida dos pacientes com adenocarcinoma gástrico.
7 PERSPECTIVAS
1- Avaliar a expressão protéica e quantificar os níveis de mRNA dos genes da família bcl-2 e das caspases por meio da técnica de Western-Blot e pela técnica de PCR-RT respectivamente, em material congelado do mesmo grupo de pacientes estudado, para correlacionar com os achados imuno-histoquímicos observados neste estudo.
2- Correlacionar os achados imuno-histoquímicos observados nos adenocarcinomas
com a resposta dos pacientes à quimioterapia, para verificar a influência da hiperexpressão da proteína Bcl-xl, que facilita a resistência a este tipo de tratamento, assim como verificar a influência da hipoexpressão da proteína Bak nos adenocarcinomas, conhecida por sensibilizar as células neoplásicas ao tratamento quimioterápico. (111)
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Abstract
In cases of gastric carcinoma, to contribute to knowledge of the process
of carcinogenesis:
Purpose: To study the immunoexpression of Bcl-2 family proteins (Bcl-2, Bcl-xl, Bax,
Bak, Bad) and to evaluate the correlation between the immunoexpression of these proteins with the cleaved caspases 3, Ki-67 and p53 immuno-expression. Methods: A TMA paraffin block was constructed with gastric carcinoma tissue (test group) and normal gastric adjoining mucosa (control group) of 87 patients. The TMA block was submitted to immunohistochemistry for Bcl-2, Bcl-xl, Bax, Bak, Bad, p53 and-cleaved Caspase 3. Results: All studied proteins were present in tumor and normal gastric adjoining mucosa, but with different intensity and amount of positive cells. i) There was an association between tumor size and p53 expression. ii) association between Bad expression in the tumor and patient’s age. iii) Intestinal type adenocarcinoma was positively correlated with the expression of Bax, Bad and Ki-67. iv) The protein Bcl-xl, Bak, Bad, p53 and Ki-67 showed statistically significant differences between the immuno-expression in tumor and normal gastric adjoining mucosa. v) There was an association between the proteins Bax, Bak and Bad expression in the normal gastric adjoining mucosa. vi) No correlation between patient’s survival rates and the expression of the proteins was observed. Conclusions: The higher expression of Bcl-xl protein in adenocarcinoma, the difference of Bcl-xl expression between test group and control group, might be related with the anti-apoptotic effect of this protein. The lower expression of Bak and Bad and the increased expression of p53 protein and Ki-67 protein in adenocarcinomas demonstrate the imbalance between death and cellular proliferation, which allows the uncontrolled tumor cell proliferation.
Keywords: 1. Gastric cancer,2. apoptosis, 3. Family Bcl-2, 4- Immunohistochemestry. 5. Tissue microarray, 6. Prognosis.