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The lysosomal protease cathepsin D is associated with tumor progression in malignant tumors, but its presence in pre-malignant dysplastic cells has not been established. The purpose of this study is to evaluate the expression patterns of the cathepsin D, Ki-67, and p53 proteins in dysplastic cells in uterine cervical intraepithelial neoplasias (CINs). In 52 patients with uterine CINs, expression of the cathepsin D, Ki-67, and p53 proteins was assessed in dysplastic cells by immunohistochemistry with monoclonal antibodies against cathepsin D, Ki-67, and p53. Immunohistochemical analysis revealed high levels of cathepsin D (>10% cathepsin D-positive dysplastic cells) in 3 of 17 cervical intraepithelial neoplasia (CIN) 1 specimens, 16 of 20 CIN2 specimens, and in all 15 CIN3 specimens. Cathepsin D expression was significantly higher in CIN2 and CIN3 specimens than in CIN1 specimens (P < 0.01). but did not differ significantly between CIN2 and CIN3 specimens. The proportion of dysplastic cells that expressed nuclear Ki-67 was 26.41% in CIN1 specimens, 50.35% in CIN2 specimens, and 76.33% in CIN3 specimens. Ki-67-positive dysplastic cells were significantly increased in CIN2 and CIN3 specimens as compared to CIN1 specimens (P < 0.01), and in CIN3 specimens as compared to CIN2 specimens (P < 0.01). High expression of nuclear p53 (>10% p53positive dysplastic cells) was detected in 4 of 17 CIN1 specimens, 12 of 20 CIN2 specimens, and in 11 of 15 CIN3 specimens. Nuclear p53 expression was significantly higher in CIN2 and CIN3 specimens than in CIN1 specimens (P < 0.01), but did not differ significantly between CIN2 and CIN3 specimens. Compared to dysplastic cells in CIN1, dysplastic cells in CIN2 have an increased invasive growth potential, as shown by their increased expression of cathepsin D, a higher proliferating potential as shown by their increased expression of Ki-67, and a higher p53 expression.

The Expression of Cathepsin D in Uterine Cervical Intraepithelial Neoplasia Correlates with the Nuclear Expression of Ki-67 and p53