HER-2/neu in Breast Cancer

Abstract

HER-2/neu is a protooncogene frequently overexpressed in breast cancer. Fluorescence in situ hybridization (FISH) is a technique targeting the gene amplification, while immunohisto-chemistry detects the protein expression. Usually both are applied to paraffin-embedded tissue. The authors studied HER-2 by FISH and immunohistochemistry (HercepTest) in 81 breast carcinomas. The results showed an overall concordance (correlation coefficient 0.64). In all cases with HercepTest score 0 and 1+, nonamplification of the gene was observed. Gene amplification was found in 20% of cases with a 2+ score and in 77.78% of cases with a 3+ score. Data described in literature for 3+ carcinomas showed a 3% to 10% discrepancy between protein expression and gene amplification, while in this study this difference was up to 22.22%. As a consequence, even if it is usually considered important to analyze only 2+ cases by FISH, 3+ scores nonamplified for HER-2/neu may be a new, interesting subset. Furthermore, the authors investigated the two-variables correlation between chromosome 17 copy number, protein over-expression, gene amplification, and presence of metastatic lymph nodes. Interesting results came from the correlation between the HercepTest score and the HER-2/neu gene amplification evaluation, HercepTest and chromosome 17 aneusomy, and gene amplification and lymph nodes status. In conclusion, the FISH technique can be an important and useful diagnostic tool to integrate the results of the HercepTest and to select patients for immunotherapy.

Testing for HER2 in Breast Cancer: A Continuing Evolution

“…Of the 54 cases with 2+ staining, only 26 (48%) showed HER2 gene amplification by FISH [156]. Several other studies have also shown absence of gene amplification in subset of cases which were scored 2+ by IHC [147, 149, 153, 154, 157, 158]. Hence, a combined approach with IHC and FISH analysis was recommended for accurate HER2 testing particularly for cases with moderate staining with IHC [137, 148, 149, 152, 157].…”

“…Several studies have identified a subset of false positive breast cancers that are IHC 3+ and negative by FISH ranging from 3% to 22% of all positive cases [146, 148, 153, 156–158, 160]. These inconsistencies may be due to several causes including variability in tissue fixation and processing, intratumoral heterogeneity, and polysomy of chromosome 17 [166, 167].…”

Tag-Mass: Specific Molecular Imaging of Transcriptome and Proteome by Mass Spectrometry Based on Photocleavable Tag

“…Tagged photocleavable linkers can be chemically attached to different classes of probes such as DNA, cDNA, single stranded cRNA, or antibody probes. They can then be used in conjunction with classical tissue-specific molecular targeting using either hybridization methods for oligonucleotides with In Situ Hybridization (ISH) or paratope-epitope interaction with immuhistochemistry (IHC) approach for antibody probes 1 (A) Schematic representation of the concept of MALDI imaging of mRNA using tagged oligonucleotide probes for detection by photocleavage.…”