The impact of KRAS mutations on prognosis in surgically resected colorectal cancer patients with liver and lung metastases: a retrospective analysis

Hae Su Kim, Jin Seok Heo, Jeeyun Lee, Ji Yun Lee, Min-Young Lee, Sung Hee Lim, Woo Yong Lee, Seok Hyung Kim, Yoon Ah Park, Yong Beom Cho, Seong Hyeon Yun, Seung Tae Kim, Joon Oh Park, Ho Yeong Lim, Yong Soo Choi, Woo Il Kwon, Hee Cheol Kim, Young Suk Park

KRAS mutations are common in colorectal cancer (CRC). The role of KRAS mutation status as a prognostic factor remains controversial, and most large population-based cohorts usually consist of patients with non-metastatic CRC. We evaluated the impact of KRAS mutations on the time to recurrence (TTR) and overall survival (OS) in patients with metastatic CRC who underwent curative surgery with perioperative chemotherapy. Patients who underwent curative resection for primary and synchronous metastases were retrospectively collected in a single institution during a 6 year period between January 2008 and June 2014. Patients with positive surgical margins, those with known BRAF mutation, or those with an unknown KRAS mutation status were excluded, and a total of 82 cases were identified. The pathological and clinical features were evaluated. Patients' outcome with KRAS mutation status for TTR and OS were investigated by univariate and multivariate analysis. KRAS mutations were identified in 37.8 % of the patients and not associated with TTR or OS between KRAS wild type and KRAS mutation cohorts (log-rank p = 0.425 for TTR; log-rank p = 0.137 for OS). When patients were further subdivided into three groups according to mutation subtype (wild-type vs. KRAS codon 12 mutation vs. KRAS codon 13 mutation) or amino acid missense mutation type (G > A vs. G > T vs. G > C), there were no significant differences in TTR or OS. Mutational frequencies were significantly higher in patients with lung metastases compared with those with liver and ovary/bladder metastases (p = 0.039), however, KRAS mutation status was not associated with an increased risk of relapsed in the lung. KRAS mutation was not associated with TTR or OS in patients with metastatic CRC who underwent curative surgery with perioperative chemotherapy.