Expression And Significance Of P21, P27, Cyclin D1 And CPP32 In Paget's Disease

Lots of studies in recent years have revealed that uncontrolled cell cycle plays an important role in cell over-proliferation, which ultimately results in cell carcinogenesis. It is well known that cell cycle in eukaryotic cells is controlled by various complexes composed of cyclin and cyclin dependent kinase (CDK). As a novel protein identified by human, cyclin dependent kinase inhibitor (CDI) could combine with cyclin-CDK complexes, and inhibit the activity of those complexes. As a result, CDI arrests the transition from Gl phase to S phase in cell cycle and slowers the progression of cell proliferation, suggesting that acts as anti-oncogene product.. Now it is generally accepted that p21 and p27 are two broad-spectrum proteins in CDI family, which could block the cell cycle at Gl phase by preventing Rb protein from phosphorylation. There have been a few speculations about whether the abnormal expression of p21 or p27 is relevant to the initiation and development of tumors. Recent studies identified another oncogene-cyclin Dl gene, whose encoded protein cyclin Dl is essential for the transition from Gl phase to S phase in cell cycle and associates closely with the initiation of tumors. The abnormal regulation of cell cycle usually accompanies aberrant mechanisms during cell death or cellapoptosis. CPP32 plays a pivotal role in cascade reactions of caspases's proteases via catalyzing various substrates; while at the same time caspases function as a new factor in the regulation of apoptosis. CPP32 participates in a wide variety of physiological and pathological processes. Thus, detection for CPP32 expression may be helpful to elucidate mechanisms during tumor development.Paget's disease which is a special skin tumor could be divided into two groups: mammary Paget's disease and exmammary Paget's disease. However, the mechanism for Paget's disease as well as its histological origin remains unclear. Up to date there's no report about expression or significance of p21, p27, cyclin Dl and CPP32 in Paget's disease in literature, although a few researchers have studied the expression and significance of these indexes in some skin tumors. In this study, we investigate the role of p21, p27, cyclin Dl and CPP32 in initiation and development of Paget's disease. It is our objective that the results may provide a novel insight and means in clinical diagnosis and prognosis for Paget's disease.Materials and methodsFifty-two paraffin biopsies of patients with Paget's disease including thirty MPD biopsies and twenty-two EMPD ones were collected from the files of the first and second affiliated hospital, Zhejiang University from 1986 to 2001. In addition, twelve biopsies from healthy mammary gland tissue, twelve ones from healthy skin and eight ones from vulva skin were collected as control. Immunohistochemical SP method was performed to examine the expression ofp21, p27, cyclin Dl and CPP32. Primary antibody was used at a dilution of 1:25, 1:50, 1:75 and 1:50 respectively, while positive control and negative control were also established. The results were evaluated semiquantitatively and graded into 4 scales according to the percentage of positive cell and staining intensity respectively: negative (-), mild positive (+), moderate positive (++), strong positive (+++). The data were analyzed by J2test, and the correlation was determined by Kendall method. K-m's existence analysis method was used to evaluate the survival state and Log-rank method was performed to analyze the difference of survival state among groups.Results and discussionThere were 16 positive cases for p21 in 30 MPD cases, and the positive rate was 53.3% lower than that in normal mammary gland group, which was 91.7%, showing a statistically difference (P<0.05). In 22 EMPD cases, there were 15 positive ones for p21 with a positive rate of 63.0%, which was remarkably lower than that in normal skin group and vulva skin group (P<0.05). And we found the expression for p21 in MPD has links with patient age., The expression for p21 in patients...