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Epidermal growth factor receptor immunohistochemistry: new opportunities in metastatic colorectal cancer.

Hutchinson RA, Adams RA, McArt DG, Salto-Tellez M, Jasani B, Hamilton PW - J Transl Med (2015)

Bottom Line: Immunohistochemistry is widely used in the fields of diagnostic and personalised medicine to localise and visualise disease specific proteins.To date the clinical utility of epidermal growth factor receptor immunohistochemistry in determining monoclonal antibody efficacy has remained somewhat inconclusive.In this review we explore the reasons behind this with a particular emphasis on colorectal cancer, and to suggest a way of resolving the situation through improving the precision of epidermal growth factor receptor immunohistochemistry with quantitative image analysis of digitised images complemented with companion molecular morphological techniques such as in situ hybridisation and section based gene mutation analysis.

View Article: PubMed Central - PubMed

Affiliation: Centre for Cancer Research and Cell Biology, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7AE, Northern Ireland, UK. ryan.hutchinson@unimelb.edu.au.

ABSTRACT
The treatment of cancer is becoming more precise, targeting specific oncogenic drivers with targeted molecular therapies. The epidermal growth factor receptor has been found to be over-expressed in a multitude of solid tumours. Immunohistochemistry is widely used in the fields of diagnostic and personalised medicine to localise and visualise disease specific proteins. To date the clinical utility of epidermal growth factor receptor immunohistochemistry in determining monoclonal antibody efficacy has remained somewhat inconclusive. The lack of an agreed reproducible scoring criteria for epidermal growth factor receptor immunohistochemistry has, in various clinical trials yielded conflicting results as to the use of epidermal growth factor receptor immunohistochemistry assay as a companion diagnostic. This has resulted in this test being removed from the licence for the drug panitumumab and not performed in clinical practice for cetuximab. In this review we explore the reasons behind this with a particular emphasis on colorectal cancer, and to suggest a way of resolving the situation through improving the precision of epidermal growth factor receptor immunohistochemistry with quantitative image analysis of digitised images complemented with companion molecular morphological techniques such as in situ hybridisation and section based gene mutation analysis.

No MeSH data available.


Related in: MedlinePlus

Inhibition of EGFR signalling can be achieved with the use monoclonal antibodies cetuximab and panitumumab in RAS wild type patients.
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Fig2: Inhibition of EGFR signalling can be achieved with the use monoclonal antibodies cetuximab and panitumumab in RAS wild type patients.

Mentions: The EGFR and downstream components of the pathway have an integral role in tumorigenesis by means of regulating proliferation, angiogenesis and metastasis [7, 8, 39] (Figure 1). EGFR inhibition can be achieved by using two classes of drugs, tyrosine kinase inhibitors or monoclonal antibodies [44]. Cetuximab and panitumumab are monoclonal antibodies that bind specifically to both EGFR homodimers and its heterodimers [39, 40, 44]. Cetuximab is an IgG1 chimerised, monoclonal antibody containing 34% mouse protein, which binds specifically to EGFR and its heterodimers [45] (Figure 2). Panitumumab is a fully humanised IgG2 antibody and has been found to have less hypersensitivity reactions compared to cetuximab [46]. KRAS and NRAS mutations have been identified as negative predictive markers for cetuximab and panitumumab efficacy in colorectal cancer [47–50] (Figure 2). This mutation is now used in current clinical practice to stratify patients eligible for cetuximab administration. However, recent studies identified that tumours with a KRAS wild type (KRAS WT) and positive EGFR expression as measured by IHC was not predictive of anti-EGFR efficacy [20, 42, 50, 51].Figure 1


Epidermal growth factor receptor immunohistochemistry: new opportunities in metastatic colorectal cancer.

Hutchinson RA, Adams RA, McArt DG, Salto-Tellez M, Jasani B, Hamilton PW - J Transl Med (2015)

Inhibition of EGFR signalling can be achieved with the use monoclonal antibodies cetuximab and panitumumab in RAS wild type patients.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4492076&req=5

Fig2: Inhibition of EGFR signalling can be achieved with the use monoclonal antibodies cetuximab and panitumumab in RAS wild type patients.
Mentions: The EGFR and downstream components of the pathway have an integral role in tumorigenesis by means of regulating proliferation, angiogenesis and metastasis [7, 8, 39] (Figure 1). EGFR inhibition can be achieved by using two classes of drugs, tyrosine kinase inhibitors or monoclonal antibodies [44]. Cetuximab and panitumumab are monoclonal antibodies that bind specifically to both EGFR homodimers and its heterodimers [39, 40, 44]. Cetuximab is an IgG1 chimerised, monoclonal antibody containing 34% mouse protein, which binds specifically to EGFR and its heterodimers [45] (Figure 2). Panitumumab is a fully humanised IgG2 antibody and has been found to have less hypersensitivity reactions compared to cetuximab [46]. KRAS and NRAS mutations have been identified as negative predictive markers for cetuximab and panitumumab efficacy in colorectal cancer [47–50] (Figure 2). This mutation is now used in current clinical practice to stratify patients eligible for cetuximab administration. However, recent studies identified that tumours with a KRAS wild type (KRAS WT) and positive EGFR expression as measured by IHC was not predictive of anti-EGFR efficacy [20, 42, 50, 51].Figure 1

Bottom Line: Immunohistochemistry is widely used in the fields of diagnostic and personalised medicine to localise and visualise disease specific proteins.To date the clinical utility of epidermal growth factor receptor immunohistochemistry in determining monoclonal antibody efficacy has remained somewhat inconclusive.In this review we explore the reasons behind this with a particular emphasis on colorectal cancer, and to suggest a way of resolving the situation through improving the precision of epidermal growth factor receptor immunohistochemistry with quantitative image analysis of digitised images complemented with companion molecular morphological techniques such as in situ hybridisation and section based gene mutation analysis.

View Article: PubMed Central - PubMed

Affiliation: Centre for Cancer Research and Cell Biology, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7AE, Northern Ireland, UK. ryan.hutchinson@unimelb.edu.au.

ABSTRACT
The treatment of cancer is becoming more precise, targeting specific oncogenic drivers with targeted molecular therapies. The epidermal growth factor receptor has been found to be over-expressed in a multitude of solid tumours. Immunohistochemistry is widely used in the fields of diagnostic and personalised medicine to localise and visualise disease specific proteins. To date the clinical utility of epidermal growth factor receptor immunohistochemistry in determining monoclonal antibody efficacy has remained somewhat inconclusive. The lack of an agreed reproducible scoring criteria for epidermal growth factor receptor immunohistochemistry has, in various clinical trials yielded conflicting results as to the use of epidermal growth factor receptor immunohistochemistry assay as a companion diagnostic. This has resulted in this test being removed from the licence for the drug panitumumab and not performed in clinical practice for cetuximab. In this review we explore the reasons behind this with a particular emphasis on colorectal cancer, and to suggest a way of resolving the situation through improving the precision of epidermal growth factor receptor immunohistochemistry with quantitative image analysis of digitised images complemented with companion molecular morphological techniques such as in situ hybridisation and section based gene mutation analysis.

No MeSH data available.


Related in: MedlinePlus