Cyclin E expression and outcome in pancreatic ductal adenocarcinoma.
The association of high cyclin E expression with poor outcome in some cancers, in particular breast cancer, suggests that it may play an important role in tumor biology. Because the influence of cyclin E expression on outcome is yet to be examined in pancreatic cancer, we assessed the relationship between the expression of cyclin E, p27(Kip1), and survival in a large cohort of pancreatic cancer patients with long-term follow-up. Expression of cyclin E and p27(Kip1) was assessed by immunohistochemistry using tissue microarrays of tumor samples from 118 patients with pancreatic ductal adenocarcinoma (75 resections and 43 biopsies). High cyclin E expression (>10% positive nuclei) was identified in 39 of 118 (33%) patients. This was associated with poor prognosis on univariate analysis in the whole cohort (P = 0.005), as well as in the subgroup of 75 patients who underwent operative resection (P = 0.04). On multivariate analysis, high cyclin E expression was an independent predictor of poor survival in both the entire cohort (P = 0.005) and the resected subgroup (P = 0.03), and was superior to all tested clinicopathologic factors (tumor size, lymph node metastases, differentiation, margin involvement, and perineural invasion) as a marker of survival. Low p27(Kip1) expression (<5% positive nuclei) was present in 41 of 111 (37%) patients, but was not associated with survival, and coexpression of p27(Kip1) did not influence the association of high cyclin E expression with poor survival. High cyclin E expression is a strong independent predictor of poor outcome in patients with pancreatic cancer. Thus, if these data are confirmed in independent cohorts, measurement of cyclin E may add significant prognostic information to the currently used clinicopathologic variables and hence have potential clinical utility in the management of this disease.
Skalicky
David A
DA
Cancer Research Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, New South Wales 2010, Australia.
Kench
James G
JG
Segara
Davendra
D
Coleman
Maxwell J
MJ
Sutherland
Robert L
RL
Henshall
Susan M
SM
Musgrove
Elizabeth A
EA
Biankin
Andrew V
AV
D000230:Adenocarcinoma / Q000737:chemistry* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001315:Australia; D014408:Biomarkers, Tumor / Q000032:analysis*; D019927:Cyclin E / Q000032:analysis*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000032:analysis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010180:Pancreatectomy; D010183:Pancreatic Ducts / Q000737:chemistry* / Q000473:pathology* / Q000601:surgery; D010190:Pancreatic Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D011237:Predictive Value of Tests; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D019927:Cyclin E; D050760:Cyclin-Dependent Kinase Inhibitor p27