Abstract
Considerable attention has been given to the accuracy of HER-2 testing and the correlation between the results of different testing methods. This interest reflects the growing importance of HER-2 status in the management of patients with breast cancer. In this study the detection of HER-2 gene and centromere 17 status was evaluated using dual-colour primed in situ labelling (PRINS) in comparison with fluorescence in situ hybridization (FISH). These two methods were evaluated on a series of 27 formalin fixed paraffin embedded breast carcinoma tumours, previously tested for protein overexpression by HercepTest (grouped into Hercep 1+/0, 2+ and 3+). HER-2 gene amplification (ratio ≥ 2.2) by PRINS was found in 3:3, 6:21 and 0:3 in IHC 3+, 2+ and 1+/0 cases, respectively. Comparing FISH and IHC (immunohistochemistry), showed the same results as for PRINS and IHC. Chromosome 17 aneusomy was found in 10 of 21 IHC 2+ cases (47.6%), of which 1 (10%) showed hypodisomy (chromosome 17 copy number per cell ≤ 1.75), 7 (70%) showed low polysomy (chromosome 17 copy number per cell=2.26 - 3.75) and 2 (20%) showed high polysomy (chromosome 17 copy number per cell ≥ 3.76). The overall concordance of detection of HER-2 gene amplification by FISH and PRINS was 100% (27:27). Furthermore, both the level of HER-2 amplification and copy number of CEN17 analysis results correlated well between the two methods. In conclusion, PRINS is a reliable, reproducible technique and in our opinion can be used as an additional test to determine HER-2 status in breast tumours.
Highlights
ERBB2/HER-2 (HER-2/neu, NEU, NGL, HER-2, TKR1, CD340) is a 185 kDa transmembrane growth factor receptor and one of the four members of type 1 growth factor receptor family, designated HER1 to HER4 (c-erbB-1 to c-erbB-4)
The HER-2 status of normal or amplified was assigned to all breast cancer slides based on the HER2:centromere 17 (CEN-17) ratio determined in both the dual-colour primed in situ labelling (PRINS) and fluorescence in situ hybridization (FISH) protocols
From 21 IHC 2+ cases, 6 cases showed HER-2 gene amplification, 1 HER-2 gene deletion and the rest (14 cases) showed no HER-2 gene amplification when assessed by FISH and PRINS
Summary
ERBB2/HER-2 (HER-2/neu, NEU, NGL, HER-2, TKR1, CD340) is a 185 kDa transmembrane growth factor receptor and one of the four members of type 1 growth factor receptor family, designated HER1 to HER4 (c-erbB-1 to c-erbB-4). 20–30% of breast carcinomas and probably a higher percentage in the more malignant subgroups that form lymph node or distant metastases show altered HER-2 expression (Eccles, 2002; Carlsson et al, 2004). This is manifested as gene amplification and/or protein overexpression (Ross and Fletcher, 1999). It has been shown in many studies that overexpression of the HER-2 protein correlates with amplification of the HER-2 gene (Tubbs et al, 2000) These alterations are associated with shorter disease free period and overall survival and with resistance to tamoxifen antiestrogen therapy and other chemotherapy regimens, regardless of the nodal or hormone receptor status (Tetu et al, 1998). Patients suffering breast carcinoma presenting HER-2 amplification or overexpression can benefit from anthracycline-based regimens, as well as trastuzumab (Cobleigh et al, 1999)
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