Diversity in expression and prognostic significance of G1/S cyclins in human primary lung carcinomas.

Expression of cyclin A, cyclin E and cdk2 was examined immunohistochemically in 144 cases of primary non-small cell lung carcinoma to evaluate their prognostic value. Cyclin A was co-expressed with cdk2 in the proliferating cells, ie those showing positive Ki-67 staining. The labelling index (LI) of cyclin A revealed a positive correlation with the S-phase fraction and an inverse correlation with histological differentiation. Furthermore, high cyclin A LIs indicated a poor prognosis in all histological types. Cyclin E exhibited a characteristic staining pattern: in squamous cell carcinoma (SCC), differentiated cells without Ki-67 staining revealed cyclin E positivity with expression of cdk2. Conversely, in adenocarcinoma (AC), proliferating cells revealed cyclin E positivity. Cases of large cell carcinoma showed heterogeneous cyclin E staining patterns, unlike those of SCC or AC. Statistical analyses also revealed a marked contrast between SCC and AC. In AC, the LI of cyclin E was inversely correlated with histological differentiation and a high LI predicted a worse prognosis. In contrast, in SCC, the LI of cyclin E correlated positively with histological differentiation and better prognosis. However, the expression levels of cyclin E mRNA evaluated by quantitative RT-PCR were higher in poorly differentiated SCC and AC, suggesting that protein turnover plays a large role in determining cyclin E protein levels. Although the expression of cyclins was demonstrated to be diversely regulated depending on the histological type, the combined immunohistochemical analyses performed in this study on these proteins could be useful tools for evaluating patient prognosis in lung carcinomas. Copyright 2002 John Wiley & Sons, Ltd.