Details

Autor(en) / Beteiligte

• Memon, Raima
• Prieto Granada, Carlos N.
• Harada, Shuko
• Winokur, Thomas
• Reddy, Vishnu
• Kahn, Andrea G.
• Siegal, Gene P.
• Wei, Shi

Titel

Discordance Between Immunohistochemistry and In Situ Hybridization to Detect HER2 Overexpression/Gene Amplification in Breast Cancer in the Modern Age: A Single Institution Experience and Pooled Literature Review Study

Ist Teil von

• Clinical breast cancer, 2022-01, Vol.22 (1), p.e123-e133

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• Human epidermal growth factor 2 (HER2) amplification and/or overexpression occurs in 12% to 25% of breast cancers. Accurate detection of HER2 is critical in predicting response to HER2-targeted therapy. Both immunohistochemistry (IHC) and in situ hybridization (ISH) are FDA-approved methods for detecting HER2 status because its protein overexpression is largely attributable to gene amplification. However, variable discordant results between IHC and ISH have been reported. We determined the frequency of HER2 IHC/ISH discordance in these patients and also performed a pooled literature review analysis. Of the 1125 consecutive primary or metastatic breast cancers with HER2 IHC and ISH performed simultaneously between 2015 and 2020, 84.6% had an unequivocal HER2 status. Discordance was found in 30 cases from 26 patients, including 13 IHC−/ISH+ and 17 IHC+/ISH−, representing 1.6% and 11.9% of IHC− and IHC+ cases, respectively. Review of the literature between 2001 and 2020 identified 46 relevant studies, with a total of 43,468 cases with IHC and ISH performed. The IHC−/ISH+ and IHC+/ISH− discordances were seen in all antibody clones and ISH methods used. The IHC+/ISH− discordance was significantly higher than IHC−/ISH+ (13.8% vs. 3%, P < .0001). The overall discordance constituted 4% of all cases and 5.4% of those with an unequivocal IHC status. Significantly lower incongruities for both IHC−/ISH+ and IHC+/ISH− were found in those published after 2018. The discordances probably reflect altered biology of HER2 oncogene/oncoprotein. Routinely performing both IHC and ISH may uncover such cases to prevent denial of potentially beneficial targeted therapy. Accurate detection of human epidermal growth factor 2 (HER2) is critical in predicting response to HER2-targeted therapy. Both immunohistochemistry (IHC) and in situ hybridization (ISH) are FDA-approved methods for detecting HER2 status. We found that IHC−/ISH+ and IHC+/ISH− discordance constituted 2.7% of 1125 cases and 3.2% of those with an unequivocal HER2 IHC status, representing 1.6% and 11.9% of IHC− and IHC+ cases, respectively. Review of the literature revealed a significantly higher IHC+/ISH− discordance than IHC−/ISH+.