Which breast carcinomas need HER-2/neu gene study after immunohistochemical analysis? Results of combined use of antibodies against different c-erbB2 protein domains.
OBJECTIVE
Evaluation of HER2 gene amplification in breast cancers is a compelling, routine procedure. The aim of this work was to evaluate which breast carcinomas would really benefit from HER-2/neu gene analysis.


RESULTS
We studied 130 invasive breast carcinomas by immunohistochemistry (IHC) using CB11 and TAB250 MAbs directed against different domains of the c-erbB2 molecule. From this series, we selected 106 cases (32 G1, 36 G2, and 38 G3) in which HER-2/neu gene analysis, using chromogenic in-situ hybridization (CISH), was successful. IHC results were scored using the FDA approved system with three score values: 0/1+ (negative), 2+, 3+ (positive). In addition, we developed a double scoring system with six score values (0/1+ 2+ negative, 3+, 4+, 5+, 6+ positive) obtained by summating the individual scoring values obtained with each MAb. All double scoring negative cases were non-amplified (100% sensitivity), whereas all cases scored 6+ were amplified. Double scoring values and CISH results were then correlated with grade and histological type. G1 ductal carcinomas and carcinomas of lobular and of special histological type did not show HER-2/neu amplification even in the presence of protein over-expression.


CONCLUSIONS
The combined results of IHC analysis (double scoring values) obtained using MAbs directed against different c-erbB2 domains correctly indicates the HER-2/neu gene status in 57.5% of cases. In addition, simple morphological features such as low grade and special histological type are good predictors of the non-amplification of the HER-2/neu gene in breast carcinoma.
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002863:Chromogenic Compounds; D000939:Epitopes; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D012680:Sensitivity and Specificity
D002863:Chromogenic Compounds; D000939:Epitopes; D018719:Erb-b2 Receptor Tyrosine Kinases