Mutant KRAS as a prognostic biomarker after hepatectomy for rectal cancer metastases: Does the primary disease site matter?

Neda Amini, Nikolaos Andreatos, Georgios Antonios Margonis, Stefan Buettner, Jaeyun Wang, Boris Galjart, Doris Wagner, Kazunari Sasaki, Anastasios Angelou, Jinger Sun, Carsten Kamphues, Andrea Beer, Daisuke Morioka, Inger Marie Løes, Efstathios Antoniou, Katsunori Imai, Emmanouil Pikoulis, Jin He, Klaus Kaczirek, George PoultsidesCornelis Verhoef, Per Eystein Lønning, Itaru Endo, Hideo Baba, Peter Kornprat, Federico NAucejo, Martin E. Kreis, Wolfgang L. Christopher, Matthew J. Weiss, Bashar Safar, Richard Andrew Burkhart

Research output: Contribution to journalArticlepeer-review


Background: The prognostic implication of mutant KRAS (mKRAS) among patients with primary disease in the rectum remains unknown. Methods: From 2000 to 2018, patients undergoing hepatectomy for colorectal liver metastases at 10 collaborating international institutions with documented KRAS status were surveyed. Results: A total of 834 (65.8%) patients with primary colon cancer and 434 (34.2%) patients with primary rectal cancer were included. In patients with primary colon cancer, mKRAS served as a reliable prognostic biomarker of poor overall survival (OS) (hazard ratio [HR]: 1.58, 95% CI 1.28-1.95) in the multivariable analysis. Although a trend towards significance was noted, mKRAS was not found to be an independent predictor of OS in patients with primary rectal tumors (HR 1.34, 95% CI 0.98-1.80). For colon cancer, the specific codon impacted in mKRAS appears to reflect underlying disease biology and oncologic outcomes, with codon 13 being associated with particularly poor OS in patients with left-sided tumors (codon 12, HR 1.56, 95% CI 1.22-1.99; codon 13, HR 2.10 95% CI 1.43-3.08;). Stratifying the rectal patient population by codon mutation did not confer prognostic significance following hepatectomy. Conclusions: While the left-sided colonic disease is frequently grouped with rectal disease, our analysis suggests that there exist fundamental biologic differences that drive disparate outcomes. Although there was a trend toward significance of KRAS mutations for patients with primary rectal cancers, it failed to achieve statistical significance.

Original languageEnglish (US)
Pages (from-to)417-427
Number of pages11
JournalJournal of Hepato-Biliary-Pancreatic Sciences
Issue number4
StatePublished - Apr 2022


  • KRAS mutation
  • liver metastases
  • rectal cancer

ASJC Scopus subject areas

  • Surgery
  • Hepatology


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