Purpose: To evaluate the clinical impact of the altered expression of cell cycle regulators in stage I and II breast cancers.
Materials and methods: The interaction between cyclin D1/E and p27Kip1 expressions were analyzed using tissue microarray (TMA) technology in 133 breast cancers. Data from the immunohistochemical assays of 3 molecules were merged, and analyzed, with a Ki67 labeling index of the same tumors.
Results: Cyclin D1 was expressed in 72 breast carcinomas (54.1%) and cyclin E in 60 (45.1%) out of the 133 breast carcinomas. Expressions of cyclin D1 and cyclin E were inversely related to each other, and significantly associated with the estrogen receptor (ER) expression and differentiation of the breast carcinoma. The expression of cyclin E was significantly decreased in tumors expressing cyclin D1 (p=0.022). There was a trend for cyclin D1 expression to increase in tumors expressing p27Kip1 (p=0.053), but the expression of cyclin E did not correlate with p27Kip1 expression. The Ki67 labeling index was markedly increased in tumors expressing cyclin E, whereas it was significantly decreased in the cyclin D1 or p27Kip1 expressing-tumors. From survival analysis, cyclin E expression was the only significant variable for the prediction of poor survival.
Conclusion: The abnormal expressions of cell cycle regulatory molecules are prevalent, and interrelated with each other in breast cancer. Integration of TMA technology allowed a high-throughput analysis for correlating molecular the in situ findings, with the clinico-pathologic information. Among the three molecules studied, the cyclin E had a prognostic implication for stage I and II breast cancer.
Keywords: Breast neoplasm; Cyclin D1; Cyclin E; Ki67; Prognosis; Tissue microarray; p27Kip1.