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International Journal of Colorectal Disease

Published in:

01-10-2011 | Original Article

Heterogeneous distribution of K-ras mutations in primary colon carcinomas: implications for EGFR-directed therapy

Authors: Satu Oltedal, Ole Gunnar Aasprong, Jannicke H. Møller, Hartwig Kørner, Bjørnar Gilje, Kjersti Tjensvoll, Elke M. Birkemeyer, Reino Heikkilä, Rune Smaaland, Oddmund Nordgård

Published in: International Journal of Colorectal Disease | Issue 10/2011

Abstract

Purpose

K-ras mutations predict resistance against epidermal growth factor receptor (EGFR)-directed therapy of metastatic colorectal cancer (CRC). The purpose of this study was to analyze the distribution of K-ras mutations in primary tumors and corresponding sentinel lymph nodes (SLNs) from colon cancer patients.

Methods

Tumor biopsies and SLNs from 158 patients with non-metastatic colon cancer were analyzed for K-ras mutations in codons 12 and 13 by a sensitive and quantitative peptide nucleic acid clamp PCR assay.

Results

Analyses of single fresh-frozen tumor biopsies revealed K-ras mutations in 67 (42%) of the patients. Apparently low levels of K-ras mutations in 13 of the mutated primary tumors and the presence of K-ras mutations in SLNs from seven patients with a wild-type primary tumor biopsy suggested possible intratumoral heterogeneity for 20 of the patients. To confirm this hypothesis, we analyzed tissue sections from all available formalin-fixed, paraffin-embedded (FFPE) tumor blocks from these 20 patients. Ten of the patients had a mixture of tissue sections positive and tissue sections negative for K-ras mutations, two patients had K-ras mutations in all sections, and eight patients had no detectable K-ras mutations in tumor FFPE tissue blocks. Among these eight patients, five had K-ras mutations detected in SLNs. Thus, evidence supporting a heterogeneous distribution of K-ras mutations was obtained for 15 patients.

Conclusions

Heterogeneous distribution of K-ras codon 12 and 13 mutations within primary tumor, or between primary tumor and lymph node metastases, was demonstrated for 15 (20%) of 74 colon cancer patients having K-ras mutations. This may have implications for tissue sampling routines with regard to EGFR-directed therapy of CRC, both in adjuvant and metastatic settings.

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Title: Heterogeneous distribution of K-ras mutations in primary colon carcinomas: implications for EGFR-directed therapy
Authors: Satu Oltedal
Ole Gunnar Aasprong
Jannicke H. Møller
Hartwig Kørner
Bjørnar Gilje
Kjersti Tjensvoll
Elke M. Birkemeyer
Reino Heikkilä
Rune Smaaland
Oddmund Nordgård
Publication date: 01-10-2011
Publisher: Springer-Verlag
Published in: International Journal of Colorectal Disease / Issue 10/2011
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI: https://doi.org/10.1007/s00384-011-1233-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Heterogeneous distribution of K-ras mutations in primary colon carcinomas: implications for EGFR-directed therapy

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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