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Accurate KRAS mutation testing for EGFR-targeted therapy in colorectal cancer : emphasis on the key role and responsibility of pathologists

Author
Organization
Abstract
Patients with metastatic colorectal cancer and KRAS mutation are unlikely to benefit from treatment with anti-EGFR antibodies, and testing for KRAS mutation in this setting is recommended. Pathologists have a crucial role in accurate testing for KRAS mutations, whether or not testing is performed in their own laboratory, as mutation analysis is performed on paraffin embedded tissue selected by the pathologists. The type of fixative used is a very important issue, as some fixatives do not allow molecular testing. Pathologists must select the most appropriate tumoral tissue block for KRAS mutation analysis and hence, must know the sensitivity of the KRAS mutation detection methodology utilized in their reference laboratory. It is essential that they select a tissue block that contains enough percentage of viable tumour cells, as false negative results will occur when the sample is contaminated with high levels of nontumour elements. Pathologists not only have to recognize the area of invasive carcinoma and distinguish it from non-invasive neoplastic components, but also have to estimate the percentage of necrotic debris and nontumoural elements. For tests that require a high percentage of tumour cells, macrodissection before extraction of nucleic acids is often indicated. The primary pathologists in addition are responsible for preparation of the pathology report for the tissue block on which the KRAS mutation analysis was performed and should transmit the results to the requesting clinician. Pathologists should participate in a multidisciplinary oncologic consult to achieve correct interpretation of the results e.g. in case of potential false negative results.
Keywords
KRAS mutation, EGFR, colorectal cancer, cetuximab, panitumumab, K-RAS GENE, MONOCLONAL-ANTIBODY, MOLECULAR PATHOLOGY, PREDICT RESPONSE, CARCINOMA, ACTIVATION

Citation

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Chicago
Hoorens, Anne, A Jouret-Mourin, C Sempoux, P Demetter, G De Hertogh, and E Teugels. 2010. “Accurate KRAS Mutation Testing for EGFR-targeted Therapy in Colorectal Cancer : Emphasis on the Key Role and Responsibility of Pathologists.” Acta Gastro-enterologica Belgica 73 (4): 497–503.
APA
Hoorens, A., Jouret-Mourin, A., Sempoux, C., Demetter, P., De Hertogh, G., & Teugels, E. (2010). Accurate KRAS mutation testing for EGFR-targeted therapy in colorectal cancer : emphasis on the key role and responsibility of pathologists. ACTA GASTRO-ENTEROLOGICA BELGICA, 73(4), 497–503.
Vancouver
1.
Hoorens A, Jouret-Mourin A, Sempoux C, Demetter P, De Hertogh G, Teugels E. Accurate KRAS mutation testing for EGFR-targeted therapy in colorectal cancer : emphasis on the key role and responsibility of pathologists. ACTA GASTRO-ENTEROLOGICA BELGICA. 2010;73(4):497–503.
MLA
Hoorens, Anne, A Jouret-Mourin, C Sempoux, et al. “Accurate KRAS Mutation Testing for EGFR-targeted Therapy in Colorectal Cancer : Emphasis on the Key Role and Responsibility of Pathologists.” ACTA GASTRO-ENTEROLOGICA BELGICA 73.4 (2010): 497–503. Print.
@article{8524472,
  abstract     = {Patients with metastatic colorectal cancer and KRAS mutation are unlikely to benefit from treatment with anti-EGFR antibodies, and testing for KRAS mutation in this setting is recommended. Pathologists have a crucial role in accurate testing for KRAS mutations, whether or not testing is performed in their own laboratory, as mutation analysis is performed on paraffin embedded tissue selected by the pathologists. The type of fixative used is a very important issue, as some fixatives do not allow molecular testing. Pathologists must select the most appropriate tumoral tissue block for KRAS mutation analysis and hence, must know the sensitivity of the KRAS mutation detection methodology utilized in their reference laboratory. It is essential that they select a tissue block that contains enough percentage of viable tumour cells, as false negative results will occur when the sample is contaminated with high levels of nontumour elements. Pathologists not only have to recognize the area of invasive carcinoma and distinguish it from non-invasive neoplastic components, but also have to estimate the percentage of necrotic debris and nontumoural elements. For tests that require a high percentage of tumour cells, macrodissection before extraction of nucleic acids is often indicated. The primary pathologists in addition are responsible for preparation of the pathology report for the tissue block on which the KRAS mutation analysis was performed and should transmit the results to the requesting clinician. Pathologists should participate in a multidisciplinary oncologic consult to achieve correct interpretation of the results e.g. in case of potential false negative results.},
  author       = {Hoorens, Anne and Jouret-Mourin, A and Sempoux, C and Demetter, P and De Hertogh, G and Teugels, E},
  issn         = {0001-5644},
  journal      = {ACTA GASTRO-ENTEROLOGICA BELGICA},
  keyword      = {KRAS mutation,EGFR,colorectal cancer,cetuximab,panitumumab,K-RAS GENE,MONOCLONAL-ANTIBODY,MOLECULAR PATHOLOGY,PREDICT RESPONSE,CARCINOMA,ACTIVATION},
  language     = {eng},
  number       = {4},
  pages        = {497--503},
  title        = {Accurate KRAS mutation testing for EGFR-targeted therapy in colorectal cancer : emphasis on the key role and responsibility of pathologists},
  volume       = {73},
  year         = {2010},
}

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