Evaluation of the clinical significance of HER2 amplification by chromogenic in situ hybridisation in patients with primary breast cancer.
BACKGROUND
The purpose of this study was to assess the clinical relevance of HER2 amplification by a novel chromogenic in situ hybridisation (CISH) technique in patients with primary breast cancer and to determine its relationship with other prognostic markers.


METHODS
One hundred and seventy-three breast cancer patients with a mean follow-up duration of 75 months were reanalysed in this retrospective study. Expression of HER2 in tumour tissue samples was assessed by immunohistochemistry (IHC) and CISH. Discrepant cases and tumours presenting a HER2 2+ and 3+ staining with IHC were additionally analysed by fluorescence in situ hybridisation (FISH) to exclude false-positive results.


RESULTS
HER2 overexpression and amplification was found in 24.3% and 19.1%, respectively. The clinico-pathological correlations revealed a significant association between positive HER2 status and standard prognostic factors including high tumour grade, large tumour size and absence of steroid hormone receptors. Univariate analysis indicated that HER2 overexpression and amplification were predictive for poor overall (OS) and disease-free survival (DFS). The same effect was also seen in the patient groups with node-negative as well as node-positive breast cancer. By multivariate analysis, HER2 alteration proved to be an indicator of poor prognosis, independent of tumour size, tumour grade, hormone receptor expression, nodal involvement and adjuvant therapy. CONCLUSION. HER2 expression, as assessed by CISH, is an independent marker for unfavourable prognosis in primary breast cancers.
Dandachi
Nadia
N
Institute of Pathology, Institute of Pathology, Landeskliniken Salzburg, Muellner Hauptstrasse 48, Salzburg, Austria. nadia.dandachi@klinikum-graz.at
Dietze
Otto
O
Hauser-Kronberger
Cornelia
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D002863:Chromogenic Compounds; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics
D002863:Chromogenic Compounds; D018719:Erb-b2 Receptor Tyrosine Kinases