HER2 overexpression/amplification status in colorectal cancer: a comparison between immunohistochemistry and fluorescence in situ hybridization using five different immunohistochemical scoring criteria

Abstract

Objective Although HER2 has gradually become an important therapeutic target for colorectal cancer (CRC), a unified and standard HER2 scoring system was still not established in CRC, and the debatable results of immunohistochemistry and fluorescence in situ hybridization (FISH) in CRC requires further exploration. Methods In this study, we use five immunohistochemical (IHC) scoring criteria (i.e., IRS-p, IRS-m, GEA-s, GEA-b and HERACLES) and two FISH criteria to evaluate HER2 status, and further evaluate the correlation between HER2 status and clinicopathological features, survival in a large, unselected Chinese cohort of 664 CRCs. Results Finally, we set HER2/CEP17 ratio ≥ 2.0, or an average HER2 copy number ≥ 6.0 as FISH-positive threshold and the amplification rate of HER2 gene was 7.08% (47/664).The HER2 positivity (IHC 3+) was 2.71%, 3.16%, 2.56%, 2.71% and 3.16%, according to the IHC scoring criteria of IRS-p, IRS-m, GEA-s, GEA-b and HERACLES, respectively. Set FISH results as the golden standard; receiver-operating characteristic analysis showed that IRS-p had both high sensitivity and specificity than other IHC scoring systems to evaluate HER2 status. Based on IRS-p criterion, There were significant differences in tumor differentiation (p = 0.038), lymphatic vascular invasion (p = 0.001), pN stage (p value = 0.043), and overall survival (p < 0.001) among IHC score 0–3 + groups. Meanwhile, there were significant differences in pT stage (p = 0.031), pN stage (p = 0.009) and overall survival (p < 0.001) among FISH subgroups. Conclusion The IRS-p criterion was more suitable for assessing the HER2 status in CRC patients than other IHC criteria. Whereas for FISH scoring system, only HER2/CEP17 < 2.0, meanwhile HER2cn < 4.0 and HER2cn ≥ 6.0 were subgroups with unique clinicopathological characteristics.

Low and Ultra-Low HER2 in Human Breast Cancer: An Effort to Define New Neoplastic Subtypes

“…The first problem when defining HER2 overexpression in BC patients is considering how to measure the presence of HER2 in breast cancer cells. Although HER2 gene amplification has been correctly identified by fluorescence in situ hybridization (FISH) and in situ hybridization (ISH) [ 30 ], the immunohistochemical demonstration of the corresponding HER2 oncoprotein expression is considered to be the most practical approach in laboratories [ 31 ] ( Table 1 ).…”

“…The first problem when defining HER2 overexpression in BC patients is considering how to measure the presence of HER2 in breast cancer cells. Although HER2 gene amplification has been correctly identified by fluorescence in situ hybridization (FISH) and in situ hybridization (ISH) [30], the immunohistochemical demonstration of the corresponding HER2 oncoprotein expression is considered to be the most practical approach in laboratories [31] (Table 1). The ASCO/CAP guidelines for HER2 interpretation were first introduced in 2007 [32] stating that the HER2 status should be initially assessed by IHC and subsequently confirmed by FISH in cases of equivocal results [33].…”