Evaluation of HER-2 status in breast carcinoma by fluorescence in situ hybridization and immunohistochemistry.
BACKGROUND
Evaluation of HER-2 status is essential for selecting appropriate candidates for treatment with trastuzumab, a recombinant humanized monoclonal antibody active against human epidermal growth factor receptor-2 (HER-2) protein.


METHODS
To standardize a HER-2 diagnostic system for breast cancer tissue, we compared immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) results. We studied specimens from 110 patients with invasive ductal breast cancer who underwent operation. IHC analysis was performed using HercepTestTM (Dako A/S), and results assessed according to the HercepTestTM criteria. FISH was performed using a PathVysionTM HER-2 DNA probe kit (Vysis Inc.), with specimens considered HER-2 positive if the ratio of the total HER-2 signals to chromosome 17 centromere (CEP17) signals was greater than 2.


RESULTS
FISH results were indefinite in 3 patients and positive in 24 patients (22%). IHC scores were 0 in 27 patients (25%), 1+ in 53 patients (48%), 2+ in 10 patients (9%), and 3+ in 20 patients (18%). All 20 patients with a score of 3+ by IHC were positive by FISH, with only 1 (10%) of 10 patients with an IHC score of 2+ positive by FISH.


CONCLUSIONS
Our results indicated that an IHC score of 3+ is equivalent to FISH-positivity for HER-2 diagnosis, while patients with an IHC score of 2+ should undergo FISH testing.
Ogura
Hiroyuki
H
Department of Breast Pathology, The Cancer Institute of the Japanese Foundation for Cancer Research, 1-37-1, Kami-Ikebukuro, Toshima-ku, Tokyo 170-8455, Japan.
Akiyama
Futoshi
F
Kasumi
Fujio
F
Kazui
Teruhisa
T
Sakamoto
Goi
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000592:standards; D017404:In Situ Hybridization, Fluorescence / Q000592:standards; D008875:Middle Aged; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000627:therapeutic use; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011994:Recombinant Proteins; D000068878:Trastuzumab