Clinicopathological significance and diagnostic accuracy of HER2 immunohistochemistry in colorectal cancer: a meta-analysis

Introduction: The aim of this study was to elucidate the clinicopathological significance of HER2 expression and the diagnostic accuracy of HER2 immunohistochemistry (IHC) in colorectal cancer (CRC). A total of 2,573 CRC cases from 13 eligible studies were included. Methods: We performed a meta-analysis to examine the correlations between HER2 expression and clinicopathological characteristics in CRC. Concordance analysis between HER2 IHC and in situ hybridization (ISH) and diagnostic test accuracy review was conducted. Results: The estimated rate of HER2 IHC overexpression was 0.162 (95% confidence interval [CI] 0.106-0.240). HER2 IHC overexpression was significantly correlated with lymph node metastasis and distant metastasis but not tumor depth. HER2 IHC overexpression was not correlated with overall survival. The concordance rates between IHC and ISH were 0.968 (95% CI 0.881-0.992), 0.377 (95% CI 0.225-0.557) and 0.780 (95% CI 0.390-0.952) for HER2 IHC scores of 0/1+, 2+ and 3+, respectively. The diagnostic test accuracy review of HER2 IHC revealed that the pooled sensitivity and specificity were 0.71 (95% CI 0.58-0.82) and 0.96 (95% CI 0.94-0.97), respectively. The diagnostic odds ratio and area under the summary receiver operating characteristic curve were 51.34 (95% CI 3.82-690.54) and 0.9704, respectively. Conclusions: HER2 IHC overexpression was significantly correlated with lymph node metastasis and distant metastasis. CRC cases with HER2 IHC scores of 0/1+ exhibited good agreement with the ISH data. However, additional ISH analysis is needed to confirm HER2 status in cases with IHC scores of 2+ or 3+.