PMID- 15782071 OWN - NLM STAT- MEDLINE DCOM- 20050726 LR - 20220227 IS - 0277-1691 (Print) IS - 0277-1691 (Linking) VI - 24 IP - 2 DP - 2005 Apr TI - Assessment of Her-1, Her-2, And Her-3 expression and Her-2 amplification in advanced stage ovarian carcinoma. PG - 147-52 AB - 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. FAU - Lee, Cheng-Han AU - Lee CH AD - Genetic Pathology Evaluation Centre, Vancouver General Hospital and University of BC, Vancouver, BC, Canada. FAU - Huntsman, David G AU - Huntsman DG FAU - Cheang, Maggie C U AU - Cheang MC FAU - Parker, Robin L AU - Parker RL FAU - Brown, Lindsay AU - Brown L FAU - Hoskins, Paul AU - Hoskins P FAU - Miller, Dianne AU - Miller D FAU - Gilks, C Blake AU - Gilks CB LA - eng PT - Comparative Study PT - Journal Article PL - United States TA - Int J Gynecol Pathol JT - International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists JID - 8214845 RN - 0 (Biomarkers, Tumor) RN - EC 2.7.10.1 (ErbB Receptors) RN - EC 2.7.10.1 (Receptor, ErbB-2) RN - EC 2.7.10.1 (Receptor, ErbB-3) SB - IM MH - Biomarkers, Tumor/*analysis MH - Centromere MH - Chromosomes, Human, Pair 17 MH - ErbB Receptors/*biosynthesis MH - Female MH - Gene Amplification MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Middle Aged MH - Neoplasm Staging MH - Ovarian Neoplasms/genetics/*metabolism/pathology MH - Receptor, ErbB-2/*biosynthesis/genetics MH - Receptor, ErbB-3/*biosynthesis EDAT- 2005/03/23 09:00 MHDA- 2005/07/27 09:00 CRDT- 2005/03/23 09:00 PHST- 2005/03/23 09:00 [pubmed] PHST- 2005/07/27 09:00 [medline] PHST- 2005/03/23 09:00 [entrez] AID - 00004347-200504000-00007 [pii] AID - 10.1097/01.pgp.0000152026.39268.57 [doi] PST - ppublish SO - Int J Gynecol Pathol. 2005 Apr;24(2):147-52. doi: 10.1097/01.pgp.0000152026.39268.57.