"The revised 2013 ASCO/CAP guidelines can potentially lead to more patients being eligible for trastuzumab therapy..."

Tse Hui Lim, Alvin Soon Tiong Lim, Aye Aye Thike, Sim Leng Tien, and Puay Hoon Tan (2016) Implications of the Updated 2013 American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations on Human Epidermal Growth Factor Receptor 2 Gene Testing Using Immunohistochemistry and Fluorescence In Situ Hybridization for Breast Cancer. Archives of Pathology & Laboratory Medicine: February 2016, Vol. 140, No. 2, pp. 140-147.

ORIGINAL ARTICLES

Implications of the Updated 2013 American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations on Human Epidermal Growth Factor Receptor 2 Gene Testing Using Immunohistochemistry and Fluorescence In Situ Hybridization for Breast Cancer

Tse Hui Lim, MSc; Alvin Soon Tiong Lim, PhD; Aye Aye Thike, MMedSci; Sim Leng Tien, MD, FRCPA; Puay Hoon Tan, MD, FRCPath

From the Department of Pathology, The Academia, Singapore General Hospital, Singapore.

Reprints: Tse Hui Lim, MSc, Cytogenetics Laboratory, Department of Pathology, The Academia, Diagnostics Tower, Level 9, Singapore General Hopsital, 20 College Rd, Singapore 169856 (e-mail: lim.tse.hui@sgh.com.sg).

The authors have no relevant financial interest in the products or companies described in this article.

Context.— Human epidermal growth factor receptor 2 (HER2/neu) amplification is used as a predictive marker for trastuzumab treatment in breast cancer. Both immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) testing algorithms have been based on the 2007 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines. In late 2013, the guidelines were updated with new scoring criteria.

Objective. —To assess the impact of the revised ASCO/CAP recommendations on both IHC and FISH results by using the dual-color HER2/neu and centromeric FISH probes.

Design.— Retrospective analysis of 590 invasive carcinomas with concurrent IHC and dual-color HER2/neu and centromeric 17 (CEP17) FISH results, based on 2007 ASCO/CAP guidelines, was conducted from July 2011 to June 2013. With the revised guidelines, patients were recategorized and concordance rates between the 2 assays were recalculated.

Results. —Overall concordance rates for FISH and IHC decreased from 94.9% to 93.8% with reclassification. Negative FISH cases decreased from 79.1% to 69.3%. However, equivocal FISH cases were significantly increased from 0.7% to 9.5%, leading to more retesting. Both positive IHC and FISH cases were also noted to be increased, leading to more patients being eligible for trastuzumab treatment, especially those patients with concurrent HER2/neu and CEP17 polysomy. Approximately 1% of patients with initial FISH negative results were reclassified as having positive results when both the ratios and average copy number of HER2/neu were considered under the revised guidelines.

Conclusions.— The revised 2013 ASCO/CAP guidelines can potentially lead to more patients being eligible for trastuzumab therapy but additional retesting is to be expected owing to an increased number of equivocal FISH cases.