Unfavourable prognosis associated with K-ras gene mutation in pancreatic cancer surgical margins

Joseph Kim ¹, Howard A Reber ², Sarah M. Dry ², David Elashoff ³, Steven L. Chen ¹, Naoyuki Umetani ¹, Minoru Kitago ¹, Oscar J. Hines ², Kevork K. Kazanjian ², Suzanne H Hiramatsu ¹, Anton J Bilchik ¹, Sherri Yong ⁴, Margo Shoup ⁴ and Dave SB Hoon ^1*

¹ John Wayne Cancer Institute, United States
² UCLA School of Medicine, United States
³ Department of Biostatistics, UCLA, United States
⁴ Loyola University Chicago, United States

^* To whom correspondence should be addressed. E-mail: hoon{at}jwci.org.

Accepted 17 April 2006

Abstract

Background: Despite intent-to-cure surgery with negative resection margins, locoregional recurrence is common for pancreatic cancer.

Aims: To determine whether the detection of K-ras gene mutation in the histologically negative surgical margins of pancreatic cancer reflects unrecognized disease.

Patients: Seventy patients who underwent curative resection for pancreatic ductal adenocarcinoma were evaluated.

Methods: All patients had surgical resection margins (pancreatic transection and retroperitoneal) that were histologically free of invasive cancer. DNA was extracted from these paraffin-embedded surgical margins and assessed by quantitative real-time PCR to detect the KRAS gene mutation at codon 12. Detection of K-ras mutation was correlated with standard clinicopathologic factors.

Results: K-ras mutation was detected in the histologically negative surgical margins of 37 of 70 (53%) patients. A significant difference in overall survival was demonstrated between patients with margins that were K-ras mutation-positive vs -negative (median, 15 vs 55 months, respectively; P=0.0008). By univariate and multivariate analyses, detection of K-ras mutation in the margins was a significant prognostic factor for poor survival (HR 2.8, 95% CI: 1.5 to 5.3, P=0.0009; and HR 2.8, 95% CI: 1.4 to 5.5, P=0.004, respectively).

Conclusions: Detection of cells harboring K-ras mutation in histologically negative surgical margins of pancreatic cancer may represent unrecognized disease and correlates with poor disease outcome. The study demonstrates that molecular-genetic evaluation of surgical resection margins can improve pathologic staging and prognostic evaluation of patients with pancreatic ductal adenocarcinoma.

Keywords: K-ras, pancreatic cancer, quantitative RT-PCR, surgical margin

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Relevant Article

An unfavourable prognosis for pancreatic cancer indicates fields of opportunity

W Greenhalf
Gut 2006 55: 1533-1535. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

• Greenhalf, W (2006). An unfavourable prognosis for pancreatic cancer indicates fields of opportunity.. Gut 55: 1533-1535 [Full Text]