| The abnormalities of cyclin Dl and pi6 in cell cycle control are often present in the development of breast cancer. It has important significance to investigate their action in the happening and development of hyperplasia, atypical hyperplasia, and carcinoma in situ of breast. Papillomatosis of breast in our research is part of hyperplasia and atypical hyperplasia. Light papillomatosis (LP) belongs to hyperplasia while serious papillomatosis (SP) belongs to atypical hyperplasia. Ductal carcinoma in situ (DCIS) is an early stage of breast cancer. ObjectiveTo investigate the correlation of cyclin Dl, pi6 as cell cycle regulators with papillomatosis and DCIS of breast. MethodsImmunohistochemistry was used to determinate the expression of Cyclin Dl protein and p!6 protein in 40 DCIS, 40 SP and 40 LP, in situ hybridization (ISH) was used to examine Cyclin DlmRNA in 40 DCIS, 40 SP and 40 LP. Methylation of the pi6 tumor suppressor gene wasanalyzed to the cases with negative expression of pi6 protein in each group using methylation specific polymerase chain reaction (MSP). Results1 The positive rates of Cyclin Dl protein expression are 60.0% in DCIS, 50.0% in SP, 27.5% in LP, respectively. There is significant difference among three groups (^=8.929, P<0.05), but no significant difference to be found between group with DCIS and group with SP (X2-0.808, P>0.05). A significant difference of the positive rate was found in combined group DCIS with SP comparing to LP (x2=8.123, P < 0.05), and SP comparing to LP (x2=4.266, P < 0.05).2 The positive rates of p!6 protein expression are 40.0% in DCIS, 52.5% in SP, 80.0% in LP, respectively. There is significant difference among three groups (%2=13.708, P < 0.05), but no significant difference to be found between group with DCIS and group with SP (%"=!.257, P> 0.05). A significant difference of the positive rate was found in combined group DCIS with SP comparing to LP (x2=l2.430, P < 0.05), and SP comparing to LP (jf=6.765, P < 0.05).3 The intensity of pi 6 protein expression has significant difference among three groups (x2=12.411, P<0.05). The intensity of Cyclin Dl protein expression has significant difference in three groups (x2=14.650,P<0.05).4 Cyclin Dl is negatively correlated to p!6 among three groups. Rank correlation coefficient is -0.544 in DCIS, -0.459 in SP, -0.353 in LP. Correlation is significance at the 0.05 level (2-tailed).5 The positive rates of Cyclin DlmRNA expression are 62.5% in DCIS, 55.0% in SP, 22.5% in LP, respectively. There is significant difference in three groups (x2=14.531, P < 0.05),but no significant difference to be found between group with DCIS and group with SP (X2=0.464, P>0.05). A significant difference of the positive rate was found in combined group DCIS with SP comparing to LP (x2=14.079, P > 0.05),and SP comparing to LP (x^S.901, P < 0.05).6 Irnmunohistochemistiy is positive correlated to in situ hybridization in examining the expression of Cyclin Dl, no significant difference to be found between the expression of mRNA and protein of Cyclin Dl.7 Of the 24 DCIS, methylation was found in 10 cases, of the 19 SP, methylation was found in 7 case. None methylation was found in 11 LP. Conclusion1 The overexpression of Cyclin Dl mRNA and protein or the lowexpression of pi6 protein plays important roles in the transformationof LP into SP, but the transformation of SP into DCIS of breast epithelial requires the cooperation of both.2 The examination of immunohistochemistry of Cyclin Dl protein and p!6 protein and ISH of Cyclin DlmRNA can not help in separating DCIS from SP in difficult diagnostic situations.The research result approves the similar biologic characteristic in DCIC and SP.3 Methylation is one of mechanisms that cause abnormal pi6 expression and it then involves in the happening and development of breast cancer and plays role in the in the transformation of LP into SP.4 The abnormality of pi6 and cyclin Dl occurs at the sam...
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