PMID- 17945336 OWN - NLM STAT- MEDLINE DCOM- 20080115 LR - 20220227 IS - 1095-6859 (Electronic) IS - 0090-8258 (Print) IS - 0090-8258 (Linking) VI - 108 IP - 1 DP - 2008 Jan TI - An exploratory analysis of HER-2 amplification and overexpression in advanced endometrial carcinoma: a Gynecologic Oncology Group study. PG - 3-9 AB - OBJECTIVES: To investigate the frequency and potential prognostic or predictive value of HER-2 amplification or overexpression in advanced and recurrent endometrial cancers. METHODS: Immunohistochemical staining (IHC; DAKO Herceptest) and fluorescence in situ hybridization (FISH; Vysis Inc. PathVysion DNA Probe Kit) were performed on specimens collected on a randomized Gynecologic Oncology Group (GOG) protocol testing the addition of paclitaxel to doxorubicin/cisplatin. RESULTS: HER-2 overexpression (either 2+ (moderate) or 3+ (strong) immunostaining) and HER-2 gene amplification (a ratio of HER-2 copies to chromosome 17 (CEP17) copies > or = 2) were detected in 44% (104 of 234; 58 were 2+ and 46 were 3+) and 12% (21 of 182) of specimens, respectively. There was a significant increased frequency of overexpression in serous tumors vs. all others (23 of 38, 61% vs. 81 of 196, 41%, respectively, P=0.03). HER-2 amplification also appeared to be more common in serous tumors, but results were not significant (6 of 28, 21% vs. 15 of 141, 11%, P=0.12). There was a significant association between grade and HER-2 amplification among nonserous tumors, with grades 1, 2, and 3 cancers demonstrating 3%, 2%, and 21% amplification, respectively (P=0.003). Neither overexpression nor amplification predicted overall survival (OS) after adjusting for treatment and performance status. CONCLUSIONS: HER-2 amplification was more common in high grade tumors with a trend to being more common in serous tumors. There was no clear evidence for a survival difference or a difference in benefit from the addition of paclitaxel for women with HER-2 amplified or overexpressed tumors; however, power to detect clinically meaningful differences was low. FAU - Grushko, T A AU - Grushko TA AD - University of Chicago Medical Center, Chicago, IL 60637, USA. FAU - Filiaci, V L AU - Filiaci VL FAU - Mundt, A J AU - Mundt AJ FAU - Ridderstrale, K AU - Ridderstrale K FAU - Olopade, O I AU - Olopade OI FAU - Fleming, G F AU - Fleming GF CN - Gynecologic Oncology Group LA - eng GR - U10 CA027469-28/CA/NCI NIH HHS/United States GR - U10 CA037517-24/CA/NCI NIH HHS/United States GR - U10 CA037517/CA/NCI NIH HHS/United States GR - CA 37517/CA/NCI NIH HHS/United States GR - CA 27469/CA/NCI NIH HHS/United States GR - U10 CA027469/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20071018 PL - United States TA - Gynecol Oncol JT - Gynecologic oncology JID - 0365304 RN - 80168379AG (Doxorubicin) RN - EC 2.7.10.1 (Receptor, ErbB-2) RN - P88XT4IS4D (Paclitaxel) RN - Q20Q21Q62J (Cisplatin) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antineoplastic Combined Chemotherapy Protocols/therapeutic use MH - Cell Membrane/enzymology MH - Cisplatin/administration & dosage MH - Doxorubicin/administration & dosage MH - Endometrial Neoplasms/drug therapy/*enzymology/genetics/pathology MH - Female MH - Gene Amplification MH - *Genes, erbB-2 MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Middle Aged MH - Neoplasm Recurrence, Local/enzymology/genetics/pathology MH - Paclitaxel/administration & dosage MH - Receptor, ErbB-2/*biosynthesis/genetics PMC - PMC2699629 MID - NIHMS38789 EDAT- 2007/10/20 09:00 MHDA- 2008/01/16 09:00 PMCR- 2009/06/22 CRDT- 2007/10/20 09:00 PHST- 2007/04/17 00:00 [received] PHST- 2007/08/24 00:00 [revised] PHST- 2007/09/04 00:00 [accepted] PHST- 2007/10/20 09:00 [pubmed] PHST- 2008/01/16 09:00 [medline] PHST- 2007/10/20 09:00 [entrez] PHST- 2009/06/22 00:00 [pmc-release] AID - S0090-8258(07)00727-5 [pii] AID - 10.1016/j.ygyno.2007.09.007 [doi] PST - ppublish SO - Gynecol Oncol. 2008 Jan;108(1):3-9. doi: 10.1016/j.ygyno.2007.09.007. Epub 2007 Oct 18.