Limits...
Revisiting the technical validation of tumour biomarker assays: how to open a Pandora's box.

MarchiĆ² C, Dowsett M, Reis-Filho JS - BMC Med (2011)

Bottom Line: A tumour biomarker is a characteristic that is objectively measured and evaluated in tumour samples as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.Although guidelines for the development and validation of biomarkers are available, their implementation is challenging, owing to the diversity of biomarkers being developed.The term 'validation' undoubtedly has several meanings; however, in the context of biomarker research, a test may be considered valid if it is 'fit for purpose'.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biomedical Sciences and Human Oncology, University of Turin, Via Santena 7, 10126 Turin, Italy. caterina.marchio@unito.it

ABSTRACT
A tumour biomarker is a characteristic that is objectively measured and evaluated in tumour samples as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. The development of a biomarker contemplates distinct phases, including discovery by hypothesis-generating preclinical or exploratory studies, development and qualification of the assay for the identification of the biomarker in clinical samples, and validation of its clinical significance. Although guidelines for the development and validation of biomarkers are available, their implementation is challenging, owing to the diversity of biomarkers being developed. The term 'validation' undoubtedly has several meanings; however, in the context of biomarker research, a test may be considered valid if it is 'fit for purpose'. In the process of validation of a biomarker assay, a key point is the validation of the methodology. Here we discuss the challenges for the technical validation of immunohistochemical and gene expression assays to detect tumour biomarkers and provide suggestions of pragmatic solutions to address these challenges.

Show MeSH

Related in: MedlinePlus

Schematic representation of the validation process of novel biomarkers by using immunohistochemistry. A typical scenario for biomarkers evaluated by immunohistochemistry contemplates that new candidate markers are identified through screen analyses. Then, if commercially available antibodies specific to those markers are found, sections of tissue microarray (TMA) blocks containing a large number of samples are used to prove preliminary results. Whenever a new antibody is used to test a novel biomarker on tissue samples, technical validation is mandatory.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3102629&req=5

Figure 1: Schematic representation of the validation process of novel biomarkers by using immunohistochemistry. A typical scenario for biomarkers evaluated by immunohistochemistry contemplates that new candidate markers are identified through screen analyses. Then, if commercially available antibodies specific to those markers are found, sections of tissue microarray (TMA) blocks containing a large number of samples are used to prove preliminary results. Whenever a new antibody is used to test a novel biomarker on tissue samples, technical validation is mandatory.

Mentions: In the case of immunohistochemistry, a typical 'quick and easy' approach is illustrated in Figure 1. It should be noted, however, that such an approach carries with it far more pitfalls than many investigators assume. Although immunohistochemistry has been introduced in pathology laboratories for more than 25 years and is a relatively user-friendly technique, one should not forget that the results of immunohistochemical analysis may be affected by a series of preanalytical and analytical parameters [11-15].


Revisiting the technical validation of tumour biomarker assays: how to open a Pandora's box.

MarchiĆ² C, Dowsett M, Reis-Filho JS - BMC Med (2011)

Schematic representation of the validation process of novel biomarkers by using immunohistochemistry. A typical scenario for biomarkers evaluated by immunohistochemistry contemplates that new candidate markers are identified through screen analyses. Then, if commercially available antibodies specific to those markers are found, sections of tissue microarray (TMA) blocks containing a large number of samples are used to prove preliminary results. Whenever a new antibody is used to test a novel biomarker on tissue samples, technical validation is mandatory.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3102629&req=5

Figure 1: Schematic representation of the validation process of novel biomarkers by using immunohistochemistry. A typical scenario for biomarkers evaluated by immunohistochemistry contemplates that new candidate markers are identified through screen analyses. Then, if commercially available antibodies specific to those markers are found, sections of tissue microarray (TMA) blocks containing a large number of samples are used to prove preliminary results. Whenever a new antibody is used to test a novel biomarker on tissue samples, technical validation is mandatory.
Mentions: In the case of immunohistochemistry, a typical 'quick and easy' approach is illustrated in Figure 1. It should be noted, however, that such an approach carries with it far more pitfalls than many investigators assume. Although immunohistochemistry has been introduced in pathology laboratories for more than 25 years and is a relatively user-friendly technique, one should not forget that the results of immunohistochemical analysis may be affected by a series of preanalytical and analytical parameters [11-15].

Bottom Line: A tumour biomarker is a characteristic that is objectively measured and evaluated in tumour samples as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.Although guidelines for the development and validation of biomarkers are available, their implementation is challenging, owing to the diversity of biomarkers being developed.The term 'validation' undoubtedly has several meanings; however, in the context of biomarker research, a test may be considered valid if it is 'fit for purpose'.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biomedical Sciences and Human Oncology, University of Turin, Via Santena 7, 10126 Turin, Italy. caterina.marchio@unito.it

ABSTRACT
A tumour biomarker is a characteristic that is objectively measured and evaluated in tumour samples as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. The development of a biomarker contemplates distinct phases, including discovery by hypothesis-generating preclinical or exploratory studies, development and qualification of the assay for the identification of the biomarker in clinical samples, and validation of its clinical significance. Although guidelines for the development and validation of biomarkers are available, their implementation is challenging, owing to the diversity of biomarkers being developed. The term 'validation' undoubtedly has several meanings; however, in the context of biomarker research, a test may be considered valid if it is 'fit for purpose'. In the process of validation of a biomarker assay, a key point is the validation of the methodology. Here we discuss the challenges for the technical validation of immunohistochemical and gene expression assays to detect tumour biomarkers and provide suggestions of pragmatic solutions to address these challenges.

Show MeSH
Related in: MedlinePlus