The expression pattern of cyclin E during the cell cycle was studied in normal and tumour cells in culture and in tumour biopsies. This pattern was found to be abnormal in tumour cells. A triple immunostaining protocol, digital microscopy and image analysis were used to find the position of the individual cells in the cell cycle and to measure the nuclear cyclin E levels. In normal cells, the number of cyclin E-positive cells decreased rapidly when the cells entered the S-phase. In the tumour cell lines, cyclin E was not downregulated in early S-phase, as in normal cells. Instead the number of cyclin E-positive cells remained high throughout S-phase, and the cyclin E staining intensity per cell often increased during S-phase. In about half of the analysed tumour cell lines, many cells stained positive for cyclin E even in the G(2)-phase. This abnormal expression over the cell cycle of cyclin E was also found in tumour biopsies from cervical, breast and prostatic carcinomas, even though it varied greatly between individual tumours. In some tumours, the expression pattern of cyclin E was similar to that of normal cells in culture, whereas in others high cyclin E levels could be seen in S-phase cells, as in the transformed cell lines. A high percentage of cells expressing cyclin E during S- or G(2)-phase was found to be related to poor outcome (p < 0.025) in a small group of cervical carcinoma patients (n = 12).
Copyright 2003 Wiley-Liss, Inc.