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First Department of Medicine [T. M., H. D-A., F. H., T. K., S. O., Y. K.] and Second Department of Surgery [H. K.], Hokkaido University School of Medicine, Department of Surgical Pathology, Hokkaido University Medical Hospital [M. S.], and Department of Public Health, Sapporo Medical University School of Medicine [M. N.], Sapporo 060-8638, Japan
Cyclin
E is a G1 cyclin that has been shown to be one of the key regulators of
the G1-S transition and could consequently be a deregulated
molecule in tumors. In the present study, we have characterized cyclin
E expression by immunohistochemistry in 217 resected non-small cell
lung cancers (NSCLCs) and found large variations in cyclin E expression
among tumors. High-level cyclin E expression (a cyclin E-labeling index
30%), observed in 115 (53%) of 217 NSCLCs, was more frequently
found in tumors from smokers than from nonsmokers
(P = 0.001), in squamous cell carcinomas than in
nonsquamous cell carcinomas (P = 0.0002), and in
pT2–4 tumors than in pT1 tumors
(P = 0.04) by the 
2 test.
Multivariate logistic regression analysis for the correlation between
cyclin E expression and various characteristics showed a significant
association of high-level cyclin E expression with squamous cell
carcinomas (P = 0.005). Patients with tumors having
high-level cyclin E expression survived a significantly shorter time
than patients with tumors having low-level expression, both among the
151 patients with potentially curatively resected NSCLCs (5-year
survival rates, 48 and 63%, respectively; P =
0.03) and the 103 patients with p stage I NSCLCs (5-year survival
rates, 57 and 81%, respectively; P = 0.007).
High-level cyclin E expression was also a significant and independent
unfavorable prognostic factor in both patients with potentially
curatively resected NSCLCs (P = 0.01) and in those
with p stage I NSCLCs (P = 0.03) by Cox’s
proportional hazards model analysis. These findings indicate that
cyclin E may play a pivotal role for the biological behavior of NSCLCs,
and that a high level of cyclin E expression may be a new prognostic
marker for NSCLCs.
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