Impact of American Society of Clinical Oncology/College of American Pathologists guideline recommendations on HER2 interpretation in breast cancer

Shah, Sejal S.; Ketterling, Rhett P.; Goetz, Matthew P.; Ingle, James N.; Reynolds, Carol A.; Perez, Edith A.; Chen, Beiyun

doi:10.1016/j.humpath.2009.07.001

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Volume 41, Issue 1 , Pages 103-106, January 2010

Impact of American Society of Clinical Oncology/College of American Pathologists guideline recommendations on HER2 interpretation in breast cancer

Sejal S. Shah, MD
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA
Rhett P. Ketterling, MD
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA
Matthew P. Goetz, MD
- Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA
James N. Ingle, MD
- Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA
Carol A. Reynolds, MD
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA
Edith A. Perez, MD
- Department of Hematology-Oncology, Mayo Clinic, Jacksonville, FL 32224, USA
Beiyun Chen, MD, PhD
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA
- Corresponding author. Division of Anatomic Pathology, Mayo Clinic, Rochester, MN 55905, USA.

Received 28 April 2009; received in revised form 2 July 2009; accepted 9 July 2009. published online 17 September 2009.

Summary

Accurate assessment of human epidermal growth factor receptor 2 is critical for the management of patients with breast cancer. We set out to study the impact of the 2007 American Society of Clinical Oncology/College of American Pathologists guidelines on the interpretation of human epidermal growth factor receptor 2 IHC results and its correlation with fluorescence in situ hybridization results. Invasive breast carcinomas with IHC HercepTest 3+ were retrieved from the archive of Mayo Clinic Rochester. The human epidermal growth factor receptor 2 slides were rereviewed, and results were recorded as percentage of invasive tumor cells with 3+, 2+, 1+, and 0 staining intensity. Human epidermal growth factor receptor 2 gene amplification by fluorescence in situ hybridization was performed on all tumors with 3+ staining in 70% or less of tumor cells. Of the 141 cases studied, 12 cases showed intense membrane staining in 11% to 30% of the invasive tumor cells and would have been scored as 2+ according to the new American Society of Clinical Oncology/College of American Pathologists guidelines. Of these 12 cases, 6 were positive for human epidermal growth factor receptor 2 gene amplification by fluorescence in situ hybridization (ratio >2.2), 4 cases were negative (HER2/CEP17 ratio of < 1.8), and 2 cases were equivocal (ratio of 1.8-2.2). One human epidermal growth factor receptor 2–positive case showed dramatic intratumoral heterogeneity with high-level amplification (ratio of 12.2) in the IHC 3+ area and no amplification (ratio of 1.0) in the IHC 1+/2+ areas. The 2007 American Society of Clinical Oncology/College of American Pathologists guidelines down-scored 2.8% of tumors from human epidermal growth factor receptor 2–positive (IHC 3+) to human epidermal growth factor receptor 2–negative (IHC 2+ equivocal and fluorescence in situ hybridization negative) in this study. Clinical studies are needed to determine whether the updated guidelines are better at predicting response to anti–human epidermal growth factor receptor 2 therapy.

Keywords: HER2, FISH, Immunohistochemistry, Breast carcinoma