The human epidermal growth factor receptor (Her) family of receptor tyrosine 
kinases includes Her-1, Her-2, and Her-3. The overexpression of Her-1 and Her-2 
have been reported previously in surface epithelial ovarian cancer. Although up 
to one-third of ovarian carcinomas have been found to have amplification or 
overexpression of Her-2, responses to trastuzumab therapy in these patients have 
been disappointing. In this study, we examined Her-1, Her-2, and Her- 3 protein 
expression as well as the frequency of Her-2 amplification in a series of 103 
high-grade, advanced-stage (FIGO stage III or IV) ovarian surface epithelial 
carcinomas. Immunohistochemical staining using commercially available antibodies 
against Her-1-3 and fluorescence in situ hybridization (FISH) using probes 
against Her-2 and chromosome 17 centromere (CEP) were performed on a tissue 
microarray containing cores of tumor from 103 surface epithelial carcinomas (85 
serous, 6 mixed surface epithelial, 5 clear cell, 3 endometrioid, 3 
undifferentiated, 1 mucinous). Nine of 99 (9.1%) tumors were positive for Her-1 
expression and 5 of 102 (4.9%) tumors were positive for Her-2 expression, with 1 
showing strong immunoreactivity. None of the Her-1 positive tumors exhibited 
Her-2 immunoreactivity. There was no correlation between Her-1 or Her-2 
expression and survival. Using Her-2:centromere fluorescence ratios of 2.0 or 
1.5 as cutoffs in assessment of Her-2 amplification, 8 of 75 (10.7%) and 25 of 
75 (33.3%) tumors, respectively, showed Her-2 amplification. Two of eight tumors 
that showed higher level (>2) Her-2 amplification by FISH also were positive for 
Her-2 by immunohistochemistry. Only 3 of 103 tumors expressed Her-3. 
Immunoreactivity for Her-1 and Her-2 was less frequently observed in this series 
than has been previously reported. The strong correlation between Her-2 
immunostaining and amplification characteristic of breast carcinoma is not seen 
in ovarian carcinoma. These results indicated that few patients with ovarian 
carcinoma have tumors that would benefit from therapy targeted specifically 
against Her-1, Her-2, or Her-3.