ERBB-2 gene overexpression and amplification in uterine sarcomas.
BACKGROUND
The aim of this study was to determine ERBB-2 (HER-2/neu) gene alterations in different subtypes of uterine sarcomas.


METHODS
After central review, representative biopsies were immunohistochemically stained and semiquantitatively scored as negative, weakly (1+), moderately (2+), or strongly (3+) positive. Subsequently, fluorescence in situ hybridization (FISH) was performed on cases with 2+ and 3+ expression.


RESULTS
Seventy tumors (52 primaries and 18 recurrent) were evaluated. All 10 adenosarcomas, 21 endometrial stromal sarcomas, and 10 leiomyosarcomas were negative both in the primary and recurrent setting. Twenty-two primary carcinosarcomas were scored. The epithelial component was negative/1+ in 16 (73%), 2+/3+ in five (22.5%) tumors, and could not be evaluated in one case (4.5%), whereas the sarcoma component stained negative/1+ in 21 cases (95.5%) and 3+ (4.5%) in one case. In two recurrent carcinosarcomas, the epithelial component stained 3+ in both cases, whereas the sarcoma component scored negative and 1+. Amplification of the ERBB-2 gene as determined by FISH was observed in 3/7 (43%) carcinosarcomas with 2+ or 3+ overexpression, resulting in an overall 3/22 (14%) amplification rate. One out of four undifferentiated uterine sarcomas stained 2+. ERBB-2 immunopositivity (3+) and ERBB-2 amplification by FISH were confirmed in the recurrent tumor, resulting in a gene amplification rate of 1/4 in undifferentiated uterine sarcomas.


CONCLUSIONS
The current results suggest absence of ERBB-2 overexpression in uterine leiomyosarcoma, uterine adenosarcoma, and endometrial stromal sarcoma, whereas the ERBB-2 gene might have a biologic role in uterine carcinosarcoma and undifferentiated uterine sarcomas.
Amant
Frederic
F
Division of Gynecologic Oncology, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium. Frederic.amant@uz.kuleuven.ac.be
Vloeberghs
Veerle
V
Woestenborghs
Heidi
H
Debiec-Rychter
Maria
M
Verbist
Lieve
L
Moerman
Philippe
P
Vergote
Ignace
I
D018195:Adenosarcoma / Q000235:genetics / Q000378:metabolism; D002296:Carcinosarcoma / Q000235:genetics / Q000378:metabolism; D005260:Female; D005784:Gene Amplification; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase / Q000235:genetics; D007890:Leiomyosarcoma / Q000235:genetics / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics; D012509:Sarcoma / Q000235:genetics* / Q000378:metabolism; D018203:Sarcoma, Endometrial Stromal / Q000235:genetics / Q000378:metabolism; D014594:Uterine Neoplasms / Q000235:genetics* / Q000378:metabolism
D018719:Erb-b2 Receptor Tyrosine Kinases