HER-2/neu in breast cancer: a comparative study between histology, immunohistochemistry and molecular technique (FISH).

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 (Hercep-
Test) 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.