Genetic Heterogeneity Of Her2/Neu In Breast Carcinoma: A Meta Analysis

Both immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are accepted methods fordetermining clinical HER2 (or ERBB2) status. However, the reliability of IHC and FISH is questionable. The genetic heterogeneity (GH) of breast carcinoma is a major cause that makes its diagnosis and treatment far from being optimal. To clarify the impact of FISH and IHC testing on HER2 GH, a meta-analysis was performed in this study. A total of eight studies with 11478 patients retrieved from PubMed and Embase were included. A random-effects meta-analysis of all studies suggested GH was existed in FISH equivocal test (OR= 30.98, 95% CI 21.19-45.30) and IHC equivocal test (OR= 1.56, 95% CI 1.40-1.74), respectively. Further analysis indicated that the significant differences presented between GH and different HER2 expression by FISH test (x(2)= 864.23, P< 0.001), and between GH and different HER2 expression using IHC test (x(2)= 206.52, P< 0.001), respectively. Networks revealed that HER2 regulates different downstream proteins to coordinate numerous processes. Our results suggested that GH of HER2 differentially presented in a subset of HER2 amplified breast carcinomas, especially in cases with HER2 expression (FISH equivocal and IHC equivocal). There is a substantial difference in the frequency of GH among different ethnicities. HER2 GH is more likely to exist in FISH equivocal test than IHC equivocal test, and it is more convenient to document GH status by FISH test. We suggest FISH as the primary HER2 testing modality with breast carcinomas who are candidate for HER2 targeted therapy. FISH equivocal test is necessary to be further standardized in order to better define HER2 status and it is important to incorporate GH into the management of breast patients.