Immunohistochemical study of Cell Cycle Modulators in G(1)-S Transition in Clinical Breast Cancer Tissue.

In the present study, we investigated immunolocalization of the modulators of G(1)-S transition by using monoclonal or polyclonal antibodies for each of the modulators in 65 cases of clinical breast cancer. Two prominent cyclin dependent kinase(cdk)-cyclin complexes, cdk4-cyclin D and cdk2-cyclin E, were proved to have different modes of mutual expression. cdk4-positive lesions were found to equal cyclin D-expressing lesions in 55 cases, while the former were more extensive than the latter in 9 cases. On the other hand, cyclin E expression was detected in all the cases examined and was more dominant than that of cdk2/cdc2 in as many as 40 cases whereas the reverse was seen in only 1 case. Interestingly, cdk4(P<0.01)and cyclin E(P<0.05)expressions showed an inverse relationship with the tumor size and the cancer stage. A similar tendency was also detected for two other positive modulators of G(1)-S transition, indicating that cell cycle progression must be regulated by the cancer itself once it has grown to a certain extent. p21, which has been regarded as a universal inhibitor of the cell cycle, was expressed in 43.1% of the cases examined and its immunoreactivity showed an inverse relationship with lymph node metastasis(P<0.05). It also tended to be absent more frequently in T3 or larger cancers and stage III cases. Moreover, two patients who died as a result of cancer and three patients with recurrence were all p21 negative, suggesting that p21 is prognosticably the most significant of all these modulators.