In situ hybridization analysis of invasive breast carcinomas with immunohistochemically negative Her-2 status (a national multicenter study).
OBJECTIVE
The aim of this study was to determine the rate of Her-2 gene amplification in breast cancer cases with a previous negative Her-2 result as determined by immunohistochemistry (score 0 or 1).


METHODS
552 cases of invasive breast carcinoma were assessed with the contribution of 9 centers. Previous immunohistochemistry score was either 0 or 1+ in all cases. These cases were re-tested by Her-2 silver in situ hybridization in the central laboratory. Her-2 gene amplification was defined as Her-2/CEP 17 ratio of more than 2.2. Cases with a ratio between 1.8 and 2.0 were defined as equivocal and cases with a ratio of less than 1.8 were defined as negative.


RESULTS
Re-testing of the 552 cases with silver in situ hybridization showed a total of 22 cases with Her-2 gene amplification, of which 11 (3.2%) were found to be score 0, and 11 were found to be score 1+ (5.3%) by immunohistochemistry previously. Her-2 gene amplification rate of cases (score 0 and 1+) ranged from 0% to 10.48% among the centers. Polysomy was found in 28 (8.1%) of the score 0 cases and 25 (12.1%) among the score 1+ cases. Five (9.4%) of the cases with polysomy were found to be amplified, and 48 (90.6%) were not.


CONCLUSIONS
The results of the study show that a group of cases (3.98%) with a potential to benefit from anti-Her-2 therapy may be missed with the immunohistochemical method. This indicates the importance of quality assurance, especially in central laboratories with many breast cancer cases in daily practice.
Department of Pathology, 1İstanbul University, İstanbul Faculty of Medicine, İSTANBUL, TURKEY.
Sıtkı
S
Tuzlali
Ekrem
E
Yavuz
Tülay
T
Canda
Merih
M
Güray
Melin Ozgün
MO
Geçer
Yurdanur
Y
Süllü
Cem
C
Sezer
Dinç
D
Süren
Serpil Dızbay
SD
Sak
Zerrin
Z
Calay
Sennur
S
Ilvan
Suzan
S
Zorludemır
Melek
M
Ergın
Fatma Seyda
FS
Karavelı
Elif
E
Peşterelı
Fatih
F
Ozdener
Kasım
K
Ustündağ
D000293:Adolescent; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D055815:Young Adult