Histomorfometria, apoptose (Bcl-2 e Bax) e marcador de proliferação celular ki-67 em neoplasias intraepiteliais do colo uterino

Abstract

Cervical dysplasias are precursor to the squamous cell carcinoma (SCC) of the uterine cervix. Carcinogen induced mutations can be correlated with proliferative alterations. Accumulation of such mutations overlaps the genomic homeostasis and allows the super expression or sub-expression of determined genes, disturbing mitosis, apoptosis and cellular turn over. Immunohistochemical markers for cellular proliferation, (Ki-67) for apoptosis (Bax) and for cell survival (Bcl-2) still require studies in intraepithelial lesion of the uterine cervix to define their role in dysplasia to invasive carcinoma progression. In order to better understand the processes of cellular proliferation, apoptosis and turn-over in such precursory lesions, histomorphometric evaluation for mitosis and apoptosis besides immunohistochemistry reactions for Bax, Bcl-2 and Ki-67 proteins (considering reactivity, localization and intensity) were carried out in cervical biopsies. Samples were split in four groups: 1. Cervicitis (n=20), 2. Mild Dysplasia (n=20), 3. Moderate Dysplasia (n=20) and 4. Severe Dysplasia/in situ Carcinoma (n=20). Intense proliferation and apoptosis were observed in the lesions of high degree (moderate and severe dysplasias) as well as wide, intense and diffuse immunolabeling for Ki-67 and Bax. Such events were found discrete or null in groups cervicitis and light dysplasia. Bcl-2 labeling was incipient in most of the reactions but more intense in high degree lesions. Wide immunolabeling for Ki-67 and Bax are suggestive of an increased cellular turn over, supported by the histomorphometry for mitosis and apoptosis. The expression of the Bcl-2 increases with the severity of the dysplasia. In conclusion these data indicate that the pre-neoplastic process is dynamic; with apoptosis and mitosis occurring concomitantly.