Histological tumor grade correlates with HER2/c-erB-2 status in invasive breast cancer: a comparative analysis between immunohistochemical (CB11 clone and Herceptest), FISH and differential PCR procedures.

There is a growing clinical demand for analysis of the HER2/c-erbB-2 (HER2) status of breast cancer specimens because it provides valuable prognostic, predictive and therapeutic information. In this sense, a variety of methods is available for detection of HER2 status, although to date a reliable and sensitive test does not exist. In order to choose the most suitable procedure to assess HER2 status, we analyzed 102 invasive breast cancers for HER2 overexpression by means of immunohistochemistry (IHC), with the CB11 Mo-Ab and the Hercep Test kit, and for HER2 gene amplification by fluorescence in situ hyubridization (FISH) and differential PCR (dPCR). HER2 overexpression, determined by CB11 (group C) and HercepTest (2+ and 3+), was observed in 19 samples (18.6%) whereas genetic amplification was detected in 31 (30.4%) and 14 (13.7%) cases by FISH and dPCR, respectively. The majority of overexpressed/amplified specimens corresponded to high grade tumors. We found concordances of 78-80% and 93-95% between IHC vs FISH and IHC vs dPCR, respectively. Considering FISH procedure as a gold standard, we found a sensitivity and specificity of 48.4% and 94.3% for CB11 antibody, of 45.2% and 92.9% for HercepTest, and of 45.2% and for 100% for the dPCR. Thus, considering the sensitivity, specificity and the high grade of concordance between IHC and dPCR, we suggest the use of IHC for assessing HER2 status. However, due that sensitivity of IHC test is lower than FISH, we also suggest to carry out FISH on those cass in which IHC results are not definitive for its clinical evaluation.