Guidelines for human epidermal growth factor receptor 2 testing: biologic and methodologic considerations.

TY - JOUR

T1 - Guidelines for human epidermal growth factor receptor 2 testing: biologic and methodologic considerations.

AU - Sauter, Guido

AU - Lee, James

AU - Bartlett, John M S

AU - Slamon, Dennis J

AU - Press, Michael F

PY - 2009

Y1 - 2009

N2 - The goal of this review is to systematically address a number of issues raised in the American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) guidelines on testing for the human epidermal growth factor receptor 2 (HER-2) alteration. A group of investigators who are experienced in the conduct and interpretation of HER-2 assay methods reviewed the ASCO-CAP guidelines and address several areas of the HER-2 testing guidelines with a particular emphasis on biologic and methodologic considerations. Although HER-2 status determined by immunohistochemistry (IHC) and the status determined by fluorescent in situ hybridization (FISH) are significantly correlated, we feel that standard considerations of laboratory testing, including test accuracy, reproducibility, and precision, as well as the current data favor FISH over IHC assay methods for determining HER-2 status. These considerations are clearly important in clinical practice because HER2 amplification is directly linked to protein expression levels in breast cancer. However, this protein is not consistently analyzed in formalin-fixed tissues as a result of variability in fixation methods and times and the impact of fixation on HER-2 protein antigenicity. Conversely, gene amplification and FISH are significantly less dependent on tissue fixation methods, making this assay more reproducible between central and peripheral laboratories than IHC. Moreover, review of the existing data demonstrate that FISH is more strongly correlated with responsiveness to either trastuzumab or lapatinib treatment. Until other methods achieve similar test accuracy, reproducibility, and predictive value, we suggest FISH as the primary HER-2 testing modality for women with breast cancer who are candidates for HER-2-targeted therapies.

AB - The goal of this review is to systematically address a number of issues raised in the American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) guidelines on testing for the human epidermal growth factor receptor 2 (HER-2) alteration. A group of investigators who are experienced in the conduct and interpretation of HER-2 assay methods reviewed the ASCO-CAP guidelines and address several areas of the HER-2 testing guidelines with a particular emphasis on biologic and methodologic considerations. Although HER-2 status determined by immunohistochemistry (IHC) and the status determined by fluorescent in situ hybridization (FISH) are significantly correlated, we feel that standard considerations of laboratory testing, including test accuracy, reproducibility, and precision, as well as the current data favor FISH over IHC assay methods for determining HER-2 status. These considerations are clearly important in clinical practice because HER2 amplification is directly linked to protein expression levels in breast cancer. However, this protein is not consistently analyzed in formalin-fixed tissues as a result of variability in fixation methods and times and the impact of fixation on HER-2 protein antigenicity. Conversely, gene amplification and FISH are significantly less dependent on tissue fixation methods, making this assay more reproducible between central and peripheral laboratories than IHC. Moreover, review of the existing data demonstrate that FISH is more strongly correlated with responsiveness to either trastuzumab or lapatinib treatment. Until other methods achieve similar test accuracy, reproducibility, and predictive value, we suggest FISH as the primary HER-2 testing modality for women with breast cancer who are candidates for HER-2-targeted therapies.

M3 - SCORING: Zeitschriftenaufsatz

VL - 27

SP - 1323

EP - 1333

JO - J CLIN ONCOL

JF - J CLIN ONCOL

SN - 0732-183X

IS - 8

M1 - 8

ER -