Cyclin E Expression and Outcome in Pancreatic Ductal Adenocarcinoma

Abstract

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 p27Kip1 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 p27Kip1 expression (<5% positive nuclei) was present in 41 of 111 (37%) patients, but was not associated with survival, and coexpression of p27Kip1 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. (Cancer Epidemiol Biomarkers Prev 2006;15(10):1941-7)

NF45 overexpression is associated with poor prognosis and enhanced cell proliferation of pancreatic ductal adenocarcinoma

“…As a crucial regulator for cell cycle progression, increasing data indicated that cyclin E plays a crucial role in PDAC pathogenesis [23]. High cyclin E expression is a strong independent predictor of poor outcome in patients with pancreatic cancer [24]. Here we show that NF45 could regulate cyclin E expression, indicating the oncogenic function of NF45 was at least in part by promoting the expression of cyclin E (Fig.…”

Modulatory effects of EPA and DHA on proliferation and apoptosis of pancreatic cancer cells

“…The studies by Rosen et al revealed that there was a relationship between the overexpression of cyclin E in the patients with ovary carcinoma and the worse prognosis to varying degrees [7] . In addition, Skalicky et al observed the abnormal overexpression of cyclin E in pancreatic cancer cells [8] . This study also found that in the absence of EPA or DHA, the expression of cyclin mRNA in SW1990 cells was up-regulated, but after treatment with EPA or DHA, real time PCR revealed that the expression of cyclin E was inhibited by both of them in a time-dependent manner.…”

Tissue Biomarkers for Prognosis in Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-analysis

“…The remaining authors determined staining levels visually, with obvious potential for incorrect classification especially among the 23 studies (28%), which did not report blinding of the scorers from clinicopathologic details. The high proportion of independently prognostic biomarkers identified by studies using TMAs (44,46,61,85,100,103,116) highlights the importance of this high-throughput methodology allowing appropriate tissue resource rationing but also improving IHC standardization and reproducibility in large cohorts.…”

“…Including only resections carried out for pancreatic head lesions by PD the median study size was 62 (mean, 80). Eighteen studies only considered patients undergoing PD, with a further 5 including PD subgroup analysis (43,44,85,100,103).…”