Originally published as JCO Early Release 10.1200/JCO.2008.20.2358 on December 1 2008

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In Reply

Andrea Sartore-Bianchi, Salvatore Artale

Falck Division of Medical Oncology, Ospedale Niguarda Ca’ Granda, Milan, Italy

Silvio Veronese, Marcello Gambacorta

Division of Pathology, Ospedale Niguarda Ca’ Granda, Milan, Italy

Salvatore Siena

Falck Division of Medical Oncology, Ospedale Niguarda Ca’ Granda, Milan, Italy

We thank Velho et al for their interest in our study, which showed a 95% concordance rate of KRAS and BRAF status between primary and metastatic sites of colorectal carcinomas.¹ The authors refer to their previous study, in which they found a lower concordance rate (64%) between lymph node metastases and primary tumors in a cohort of 28 of 250 colorectal cancers.² Possible explanations for the discrepancy between the two concordance rates may be, first, that our patient series included only patients with stage IV disease and that of Velho et al included patients with stage 0 to IV disease, and second, that in the latter study, KRAS status was not assessed in distant metastatic sites.

In addition to our findings, full concordance of KRAS status between primary tumors and distant metastases,^3-5 and between primary tumors and regional lymph nodes,⁶ has been reported by independent investigators, supporting the notion that detection of a KRAS-activating mutation in either a primary or metastatic site is sufficient to exclude a patient from epidermal growth factor receptor–targeted monoclonal antibody therapies.

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

NOTES

published online ahead of print at www.jco.org on December 1, 2008

REFERENCES

1. Artale S, Sartore-Bianchi A, Veronese SM, et al: Mutations of KRAS and BRAF in primary and matched metastatic sites of colorectal cancer. J Clin Oncol 26:4217-4219, 2008[Free Full Text]

2. Oliveira C, Velho S, Moutinho C, et al: KRAS and BRAF oncogenic mutations in MSS colorectal carcinoma progression. Oncogene 26:158-163, 2007[CrossRef][Medline]

3. Losi L, Benhattar J, Costa J: Stability of K-ras mutations throughout the natural history of human colorectal cancer. Eur J Cancer 28A:1115-1120, 1992[CrossRef]

4. Etienne-Grimaldi MC, Formento JL, Francoual M, et al: K-Ras mutations and treatment outcome in colorectal cancer patients receiving exclusive fluoropyrimidine therapy. Clin Cancer Res 14:4830-4835, 2008[Abstract/Free Full Text]

5. Al-Mulla F, Going JJ, Sowden ET, et al: Heterogeneity of mutant versus wild-type Ki-ras in primary and metastatic colorectal carcinomas, and association of codon-12 valine with early mortality. J Pathol 185:130-138, 1998[CrossRef][Medline]

6. Zauber P, Sabbath-Solitare M, Marotta SP, et al: Molecular changes in the Ki-ras and APC genes in primary colorectal carcinoma and synchronous metastases compared with the findings in accompanying adenomas. Mol Pathol 56:137-140, 2003[Abstract/Free Full Text]

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