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

J. Kim, H. A. Reber, S. M. Dry, D. Elashoff, S. L. Chen, N. Umetani, Minoru Kitago, O. J. Hines, K. K. Kazanjian, S. Hiramatsu, A. J. Bilchik, S. Yong, M. Shoup, D. S B Hoon

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Abstract

Background: Despite intent to cure surgery with negative resection margins, locoregional recurrence is common in pancreatic cancer. Aims: To determine whether detection of K-ras gene mutation in the histologically negative surgical margins of pancreatic cancer reflects unrecognised 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 polymerase chain reaction to detect the K-ras gene mutation at codon 12. Detection of K-ras mutation was correlated with standard clinicopathological factors. Results: K-ras mutation was detected in 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 compared with negative (median 15 v 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 (hazard ratio (HR) 2.8 (95% confidence interval (CI) 1.5-5.3), p = 0.0009; and HR 2.8 (95% CI 1.4-5.5), p = 0.004, respectively). Conclusions: Detection of cells harbouring K-ras mutation in histologically negative surgical margins of pancreatic cancer may represent unrecognised disease and correlates with poor disease outcome. The study demonstrates that molecular-genetic evaluation of surgical resection margins can improve pathological staging and prognostic evaluation of patients with pancreatic ductal adenocarcinoma.

Original languageEnglish
Pages (from-to)1598-1605
Number of pages8
JournalGut
Volume55
Issue number11
DOIs
Publication statusPublished - 2006 Nov
Externally publishedYes

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ras Genes
Pancreatic Neoplasms
Mutation
Adenocarcinoma
Confidence Intervals
Margins of Excision
Survival
Codon
Paraffin
Real-Time Polymerase Chain Reaction
Molecular Biology
Multivariate Analysis
Recurrence
DNA

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Kim, J., Reber, H. A., Dry, S. M., Elashoff, D., Chen, S. L., Umetani, N., ... Hoon, D. S. B. (2006). Unfavourable prognosis associated with K-ras gene mutation in pancreatic cancer surgical margins. Gut, 55(11), 1598-1605. https://doi.org/10.1136/gut.2005.083063

Unfavourable prognosis associated with K-ras gene mutation in pancreatic cancer surgical margins. / Kim, J.; Reber, H. A.; Dry, S. M.; Elashoff, D.; Chen, S. L.; Umetani, N.; Kitago, Minoru; Hines, O. J.; Kazanjian, K. K.; Hiramatsu, S.; Bilchik, A. J.; Yong, S.; Shoup, M.; Hoon, D. S B.

In: Gut, Vol. 55, No. 11, 11.2006, p. 1598-1605.

Research output: Contribution to journalArticle

Kim, J, Reber, HA, Dry, SM, Elashoff, D, Chen, SL, Umetani, N, Kitago, M, Hines, OJ, Kazanjian, KK, Hiramatsu, S, Bilchik, AJ, Yong, S, Shoup, M & Hoon, DSB 2006, 'Unfavourable prognosis associated with K-ras gene mutation in pancreatic cancer surgical margins', Gut, vol. 55, no. 11, pp. 1598-1605. https://doi.org/10.1136/gut.2005.083063
Kim J, Reber HA, Dry SM, Elashoff D, Chen SL, Umetani N et al. Unfavourable prognosis associated with K-ras gene mutation in pancreatic cancer surgical margins. Gut. 2006 Nov;55(11):1598-1605. https://doi.org/10.1136/gut.2005.083063
Kim, J. ; Reber, H. A. ; Dry, S. M. ; Elashoff, D. ; Chen, S. L. ; Umetani, N. ; Kitago, Minoru ; Hines, O. J. ; Kazanjian, K. K. ; Hiramatsu, S. ; Bilchik, A. J. ; Yong, S. ; Shoup, M. ; Hoon, D. S B. / Unfavourable prognosis associated with K-ras gene mutation in pancreatic cancer surgical margins. In: Gut. 2006 ; Vol. 55, No. 11. pp. 1598-1605.
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title = "Unfavourable prognosis associated with K-ras gene mutation in pancreatic cancer surgical margins",
abstract = "Background: Despite intent to cure surgery with negative resection margins, locoregional recurrence is common in pancreatic cancer. Aims: To determine whether detection of K-ras gene mutation in the histologically negative surgical margins of pancreatic cancer reflects unrecognised 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 polymerase chain reaction to detect the K-ras gene mutation at codon 12. Detection of K-ras mutation was correlated with standard clinicopathological factors. Results: K-ras mutation was detected in 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 compared with negative (median 15 v 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 (hazard ratio (HR) 2.8 (95{\%} confidence interval (CI) 1.5-5.3), p = 0.0009; and HR 2.8 (95{\%} CI 1.4-5.5), p = 0.004, respectively). Conclusions: Detection of cells harbouring K-ras mutation in histologically negative surgical margins of pancreatic cancer may represent unrecognised disease and correlates with poor disease outcome. The study demonstrates that molecular-genetic evaluation of surgical resection margins can improve pathological staging and prognostic evaluation of patients with pancreatic ductal adenocarcinoma.",
author = "J. Kim and Reber, {H. A.} and Dry, {S. M.} and D. Elashoff and Chen, {S. L.} and N. Umetani and Minoru Kitago and Hines, {O. J.} and Kazanjian, {K. K.} and S. Hiramatsu and Bilchik, {A. J.} and S. Yong and M. Shoup and Hoon, {D. S B}",
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T1 - Unfavourable prognosis associated with K-ras gene mutation in pancreatic cancer surgical margins

AU - Kim, J.

AU - Reber, H. A.

AU - Dry, S. M.

AU - Elashoff, D.

AU - Chen, S. L.

AU - Umetani, N.

AU - Kitago, Minoru

AU - Hines, O. J.

AU - Kazanjian, K. K.

AU - Hiramatsu, S.

AU - Bilchik, A. J.

AU - Yong, S.

AU - Shoup, M.

AU - Hoon, D. S B

PY - 2006/11

Y1 - 2006/11

N2 - Background: Despite intent to cure surgery with negative resection margins, locoregional recurrence is common in pancreatic cancer. Aims: To determine whether detection of K-ras gene mutation in the histologically negative surgical margins of pancreatic cancer reflects unrecognised 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 polymerase chain reaction to detect the K-ras gene mutation at codon 12. Detection of K-ras mutation was correlated with standard clinicopathological factors. Results: K-ras mutation was detected in 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 compared with negative (median 15 v 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 (hazard ratio (HR) 2.8 (95% confidence interval (CI) 1.5-5.3), p = 0.0009; and HR 2.8 (95% CI 1.4-5.5), p = 0.004, respectively). Conclusions: Detection of cells harbouring K-ras mutation in histologically negative surgical margins of pancreatic cancer may represent unrecognised disease and correlates with poor disease outcome. The study demonstrates that molecular-genetic evaluation of surgical resection margins can improve pathological staging and prognostic evaluation of patients with pancreatic ductal adenocarcinoma.

AB - Background: Despite intent to cure surgery with negative resection margins, locoregional recurrence is common in pancreatic cancer. Aims: To determine whether detection of K-ras gene mutation in the histologically negative surgical margins of pancreatic cancer reflects unrecognised 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 polymerase chain reaction to detect the K-ras gene mutation at codon 12. Detection of K-ras mutation was correlated with standard clinicopathological factors. Results: K-ras mutation was detected in 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 compared with negative (median 15 v 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 (hazard ratio (HR) 2.8 (95% confidence interval (CI) 1.5-5.3), p = 0.0009; and HR 2.8 (95% CI 1.4-5.5), p = 0.004, respectively). Conclusions: Detection of cells harbouring K-ras mutation in histologically negative surgical margins of pancreatic cancer may represent unrecognised disease and correlates with poor disease outcome. The study demonstrates that molecular-genetic evaluation of surgical resection margins can improve pathological staging and prognostic evaluation of patients with pancreatic ductal adenocarcinoma.

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