Expression of p16 and Cyclin-Dependent Kinase 4 Proteins in Primary Breast Carcinomas

Abstract

The immunolocalization of the pl6 and cdk4 proteins was investigated in 65 retinoblastoma gene product (pRB)-positive and 20 pRB-negative breast carcinomas. These proteins were expressed in similar lesions in 84.6% of the pRB-positive and 100% of the pRB-negative carcinomas. Diffuse expression of pl6 was observed in 73.8 and 70.0% of the pRB-positive and -negative cases, respectively. cdk4 and p 16 expression was significantly more heterogeneous in tumors of larger sizes and/or at higher stages. These findings suggest that p 16 can be induced regardless of pRB status and Rb gene function in primary breast carcinoma and that it modulates the cell cycle progression in association with cdk4.

Expression of cell cycle proteins in male breast carcinoma

“…In our study 76.6% of all tumors showed p16 expression (figure 1). Whereas this finding is not discrepant with another study about the expression of p16 in female breast carcinomas [52], there are other studies where half of the breast cancers in women failed to express p16 [18,54,55]. Neither the presence of p16 positive nuclei nor the lack of detectable staining in these studies was statistically significant with tumor size (figure 4), tumor differentiation or nodal status (figure 2).…”

“…Though the higher percentage of large tumors >5 cms were associated with loss of p16 expression (20% vs. 6.7% in the positives) we could not find any statistical correlation between the expression of p16 and the DFS (p = 0.06) (figure 5), nodal status (p = 0.07) (figure 2) or the stage of the disease as demonstrated in figure 3. Thus similar to other investigators despite aberrant expression, the significance of the expression of P16 in male breast cancer could not be established [52,53,55]. …”

“…p16 belongs to the CDKN2A family of proteins, another family of CDK inhibitors [18,52]. This family of proteins particularly inhibits the activity of active CDK4 and CDK6 [52]; thus, their inhibitory activity occurs primarily in the G 1 phase where it accumulates and inhibits progression to the S-phase [53] (figure 6).…”

“…This family of proteins particularly inhibits the activity of active CDK4 and CDK6 [52]; thus, their inhibitory activity occurs primarily in the G 1 phase where it accumulates and inhibits progression to the S-phase [53] (figure 6). Reduced expression of this protein is caused by its inactivation by deletion, mutation, or methylation [53].…”

Gene Amplification and Overexpression of CDK4 in Sporadic Breast Carcinomas Is Associated with High Tumor Cell Proliferation

“…Two previous studies on expression of CDK4 protein in breast cancer reported that immunoreactivity of CDK4 protein was found in between 80 and 95% of breast carcinomas analyzed by immunohistochemical staining. 25,26 In contrast, overexpression of CDK4 protein was detected in 19% of our series of breast cancers. This discrepancy should be attributed to the difference in applied methods, the criteria for scoring of immunoreactivity, and characteristics between the various primary carcinoma tissues used for different studies.…”