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Molecular morphometric analysis shows relative intra-tumoural homogeneity for KRAS mutations in colorectal cancer

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Abstract

KRAS mutation status has a significant role determining anti-epidermal growth factor receptor (anti-EGFR) treatment response in colon carcinoma patients. Malignant transformation is a dynamic process and therefore, it is conceivable that, at a certain point, the tumor cells’ mass might be heterogeneous for particular mutations. Therefore, the fraction of tumor cells carrying a particular mutation may be more relevant for treatment than the simple determination of presence or absence of mutation. The purpose of this study is to assess whether or not KRAS mutation status is heterogeneous and, if so, to what extent in colon carcinoma samples. Deoxyribonucleic acid was extracted from formalin-fixed paraffin-embedded samples of colon carcinoma and analyzed for the presence of KRAS mutation. The relative fraction of mutated versus wild-type KRAS alleles was evaluated by real-time polymerase chain reaction. Additionally, the relative fraction of cancer cells in the tissue sample was evaluated using computer assisted morphometric analysis. Using this data, we calculated the fraction of mutation containing cells in the samples. Colon carcinoma (169 cases) were analyzed, and a KRAS mutation was found in 75 cases (44%), of which 42 were available for morphometric analysis. In 41 (97.6%) of these cases, the fraction of mutation containing tumor cells was 50% or higher, indicating the absence of significant KRAS mutation status heterogeneity. There was a strong positive correlation (R = 0.66, P < 0.0001) between the fraction of mutated KRAS alleles and the fraction of cancer cells in the samples. The strong positive correlation between the fraction of mutated KRAS alleles and the fraction of cancer cells in the samples indicate homogeneity of KRAS mutation status in colorectal carcinoma.

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Authors and Affiliations

  1. Institute of Pathology, Rambam Health Care Campus, PO Box 9602, Haifa, 31096, Israel

    Liora Farber, Yehudit Peerless, Edmond Sabo, Ofer Ben-Izhak & Dov Hershkovitz

  2. B. Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel

    Liora Farber, Yehudit Peerless, Ofer Ben-Izhak & Dov Hershkovitz

  3. Center for Translational Genetics, B. Rappaport Institute for Research in the Medical Sciences, Technion-Israel Institute of Technology, Rambam Health Care Campus, Haifa, Israel

    Edna Efrati & Hela Elkin

  4. Legacy Heritage Clinical Research Institute, Rambam Health Care Campus, Haifa, Israel

    Edmond Sabo

Authors
  1. Liora Farber
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  2. Edna Efrati
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  3. Hela Elkin
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  4. Yehudit Peerless
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  5. Edmond Sabo
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  6. Ofer Ben-Izhak
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  7. Dov Hershkovitz
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Corresponding author

Correspondence to Dov Hershkovitz.

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Farber and Efrati contributed equally to the project.

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Farber, L., Efrati, E., Elkin, H. et al. Molecular morphometric analysis shows relative intra-tumoural homogeneity for KRAS mutations in colorectal cancer. Virchows Arch 459, 487–493 (2011). https://doi.org/10.1007/s00428-011-1158-y

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  • DOI: https://doi.org/10.1007/s00428-011-1158-y

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