Sir,
We appreciate the comment from Dr Vauthey and colleagues (Vauthey et al, 2012) on our recently published article by Kawamoto et al (2012) titled ‘KRAS mutations in primary tumours and post-FOLFOX metastatic lesions in cases of colorectal cancer’. The KRAS mutation has been regarded as one of the major ‘driver mutations’ of colorectal cancer, and its frequency is high (approximately 40%) regardless of the Dukes stage (Andreyev et al, 1998). However, the prognostic and predictive usefulness of KRAS mutations is still controversial (Karapetis et al, 2008; Van Cutsem et al, 2009; Yoshino et al, 2012). Although the suggestion raised by Dr Vauthey that adjuvant FOLFOX may provide a selection pressure favouring a chemotherapy-resistant subset enriched for KRAS mutation is interesting, we should consider it carefully. We closely examined the seven cases of stage III colorectal cancer (metastases appeared ‘after’ FOLFOX therapy) in our data set and found that only two cases (28.6%) harboured KRAS mutations. Meanwhile, among the 14 cases of stage IV cancer (metastases appeared ‘before’ FOLFOX therapy), 10 cases (71.4%) harboured KRAS codon 12 mutations and 2 additional cases had KRAS A146V or NRAS Q61H mutations in both primary and metastatic lesions. Therefore, we could not conclude that KRAS mutations were enriched in the cases that relapsed ‘after’ adjuvant FOLFOX therapy in our data set.
However, we would like to emphasise that the frequency of KRAS mutations among the cases with ‘resectable’ metastases after FOLFOX therapy reported in our article was quite high. As we reported previously, the KRAS mutation frequency of oxaliplatin-refractory ‘unresectable’ metastatic colorectal cancer in our institute was 70 out of 159 (44.0%), which is equivalent to the rates described in the previous reports (Bando et al, 2011). We cannot deny that the mutant KRAS affected the biological features of metastasised tumours, and we plan further investigations.
Change history
24 January 2013
This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication
References
Andreyev HJ, Norman AR, Cunningham D, Oates JR, Clarke PA (1998) Kirsten ras mutations in patients with colorectal cancer: the multicenter ‘RASCAL’ study. J Natl Cancer Inst 90: 675–684
Bando H, Yoshino T, Tsuchihara K, Ogasawara N, Fuse N, Kojima T, Tahara M, Kojima M, Kaneko K, Doi T, Ochiai A, Esumi H, Ohtsu A (2011) KRAS mutations detected by the amplification refractory mutation system-Scorpion assays strongly correlate with therapeutic effect of cetuximab. Br J Cancer 105: 403–406
Karapetis CS, Khambata-Ford S, Jonker DJ, O'Callaghan CJ, Tu D, Tebbutt NC, Simes RJ, Chalchal H, Shapiro JD, Robitaille S, Price TJ, Shepherd L, Au HJ, Langer C, Moore MJ, Zalcberg JR (2008) K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 359: 1757–1765
Kawamoto Y, Tsuchihara K, Yoshino T, Ogasawara N, Kojima M, Takahashi M, Ochiai A, Bando H, Fuse N, Tahara M, Doi T, Esumi H, Komatsu Y, Ohtsu A (2012) KRAS mutations in primary tumours and post-FOLFOX metastatic lesions in cases of colorectal cancer. Br J Cancer 107: 340–344
Van Cutsem E, Köhne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, D'Haens G, Pintér T, Lim R, Bodoky G, Roh JK, Folprecht G, Ruff P, Stroh C, Tejpar S, Schlichting M, Nippgen J, Rougier P (2009) Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 360: 1408–1417
Vauthey JN, Kopetz S, Aloia TA, Andreou A (2012) Comment on ‘KRAS mutations in primary tumours and post-FOLFOX metastatic lesions in cases of colorectal cancer’. Br J Cancer 107: 1442–1443
Yoshino T, Mizunuma N, Yamazaski K, Nishina T, Komatsu Y, Baba H, Tsuji A, Yamaguchi K, Muro K, Sugimoto N, Tsuji Y, Moriwaki T, Esaki T, Hamada C, Tanase T, Ohtsu A (2012) TAS-102 monotherapy for pretreated metastatic colorectal cancer: a double blind, randomized, placebo-controlled phase II trial. Lancet Oncol ; e-pub ahead of print 28 August 2012
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
About this article
Cite this article
Yoshino, T., Kawamoto, Y., Bando, H. et al. Reply: KRAS mutation in colorectal cancer metastases after adjuvant folfox for the primary. Br J Cancer 107, 1444 (2012). https://doi.org/10.1038/bjc.2012.420
Published:
Issue Date:
DOI: https://doi.org/10.1038/bjc.2012.420