Contribution of fluorescence in situ hybridization to immunohistochemistry for the evaluation of HER-2 in breast cancer.
The main focus of the present study was to assess the efficacy of interphase cytogenetics using fluorescence in situ hybridization (FISH) as a valid alternative to immunohistochemistry (IHC) in paraffin-embedded tissue sections and/or the efficacy of the combination of the two methods, while, at the same time, aiming to provide additional information on the use of the two methods. For this study, selected breast cancer patients (n=66) were tested for HER-2 gene amplification by FISH. The probe contains DNA sequences specific for the HER-2 human gene locus and hybridizes to the 17q11.2 through q12 region of human chromosome 17. The same samples were tested previously for HER-2 overexpression by two monoclonal antibodies (300G9 and CB11), recognizing an extracellular and an internal domain of gp185(Her-2), respectively. HER-2 overexpression also was evaluated using the HerceptTest Kit (Dako, Milan, Italy). The HerceptTest was performed according to the manufacturer's standard procedures, and results were scored on a 0 to 3+ scale. A total of 34 (51%) of 66 breast tumors enrolled in this study were positive by FISH. Of the 34 cases amplified by FISH, 9 were negative by IHC using both monoclonal antibody (MoAb) 300G9 and MoAb CB11, with a concordance rate from 80.3% to 83.3%. A higher concordance was verified (92.4%) when we used the HerceptTest Kit. Of the 32 cases found negative with the HerceptTest, FISH analysis identified HER-2 gene amplification in more than 10%. Our results indicate that with the combined use of both methods, several amplified samples classified negative by IHC can be used thus improving therapeutic planning for specific therapy with the monoclonal antibody trastuzumab.
Cianciulli
Anna M
AM
Department of Clinical Pathology, Regina Elena Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy. cianciulli@ifo.it
Botti
Claudio
C
Coletta
Angela M
AM
Buglioni
Simonetta
S
Marzano
Raffaella
R
Benevolo
Maria
M
Cione
Antonio
A
Mottolese
Marcella
M
D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000235:genetics*; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
D018719:Erb-b2 Receptor Tyrosine Kinases