ERBB2 amplification is superior to protein expression status in predicting patient outcome in serous ovarian carcinoma.
OBJECTIVE
The objective of this study was to evaluate the frequency and clinical significance of ERBB2 gene amplification in serous ovarian carcinoma. In addition, concordance of the findings of ERBB2 immunohistochemistry and ERBB2 amplification was assessed.


METHODS
Tissue microarray constructed of 401 serous ovarian carcinomas was examined by chromogenic in situ hybridization (CISH) using probe for ERBB2 gene and by immunohistochemistry using CB11 monoclonal antibody against ERBB2 protein.


RESULTS
Amplification (>5 copies per cell) of ERBB2 was detected in 7% and low copy number increase (three-five copies) in 14% of the carcinomas. Increased copy number of ERBB2 was associated with poor prognosis, that is, poor response to therapy (P = 0.024), shorter disease-free (P < 0.0001) and overall survival (P < 0.0001). ERBB2 copy number status was identified as an independent prognostic factor for overall survival. Increased copy number of ERBB2 was also associated with high tumor grade, greater patient age, large residual tumor size, high proliferation index, aberrant p53 and negative progesterone receptor status. A significant association was found between ERBB2 amplification and ERBB2 protein overexpression. However, a substantial number of cases showed discrepant results by the two methods, especially in cases with low-level amplification or moderate protein overexpression. Overexpression of ERBB2 protein was associated with poor overall survival, but the prognostic value was weaker than that of ERBB2 gene copy number status.


CONCLUSIONS
ERBB2 amplification positive tumors identified by CISH constitute a subgroup of serous ovarian carcinomas associated with aberrant p53, negative progesterone receptor status and aggressive behavior, a suitable group for testing the effect of trastuzumab in clinical trials.
Lassus
Heini
H
Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland
Leminen
Arto
A
Vayrynen
Aki
A
Cheng
Guojun
G
Gustafsson
Jan-Ake
JA
Isola
Jorma
J
Butzow
Ralf
R
D018284:Cystadenocarcinoma, Serous / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D018572:Disease-Free Survival; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D015996:Survival Rate
D018719:Erb-b2 Receptor Tyrosine Kinases