Expression of HER2/erbB-2 correlates with survival in osteosarcoma

被引:236
作者
Gorlick, R
Huvos, AG
Heller, G
Aledo, A
Beardsley, GP
Healey, JH
Meyers, PA
机构
[1] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA
[2] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA
[3] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA
[4] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA
[5] Mem Sloan Kettering Canc Ctr, Orthopaed Serv, New York, NY 10021 USA
[6] New York Presbyterian Hosp, New York, NY USA
[7] Cornell Univ, Coll Med, New York, NY USA
[8] Yale Univ, Med Ctr, Dept Pediat, New Haven, CT USA
关键词
D O I
10.1200/JCO.1999.17.9.2781
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: In osteosarcoma, prognostic factors at diagnosis other than clinical stage have not been clearly identified. The aim of this study was to determine whether human epidermal growth factor receptor 2 (HER2)/erbB-2, p-glycoprotein, or p53 expression correlated with histologic response to preoperative chemotherapy or event-free survival. Patients and Methods: We performed a retrospective immunohistochemical study on material obtained from patients treated on the Memorial Sloan-Kettering Cancer Center T12 protocol between 1986 and 1993. paraffin-embedded tissue wets identified from 53 patients (73% of patients enrolled onto protocol) and stained for HER2/erbB-2, p53, and p-glycoprotein expression using standard monoclonal antibodies and methods, Results: At the time of initial biopsy, 20 (42.6%) of 47 samples demonstrated high levels of HER2/erbB-2 expression. Higher frequencies of expression were observed in samples from patients with metastatic disease at presentation and at the time of relapse. Expression of HER2/erbB-2 correlated with a significantly worse histologic response (P = .03). In patients presenting with nonmetastatic disease, expression of HER2/erbB-2 at the time of initial biopsy was associated with a significantly decreased event-free survival (47% v 79% at 5 years, P = .05). p53 and p-glycoprotein expression did not correlate with histologic response or patient event-free survival. Conclusion: The correlation of HER2/erbB-2 expression with histologic response to preoperative chemotherapy and event-free survival in this study suggests that HER2/erbB-2 should be evaluated prospectively as a prognostic indicator. The correlation also suggests that clinical trials of antibodies that target this receptor, such as recombinant humanized anti-HER2 monoclonal antibody (Herceptin; Genentech, San Francisco, CA), should be considered for the treatment of osteosarcoma. (C) 1999 by American Society of Clinical Oncology.
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页码:2781 / 2788
页数:8
相关论文
共 38 条
[1]  
Ahnen DJ, 1998, CANCER RES, V58, P1149
[2]   neu/erbB-2 amplification identifies a poor-prognosis group of women with node-negative breast cancer [J].
Andrulis, IL ;
Bull, SB ;
Blackstein, ME ;
Sutherland, D ;
Mak, C ;
Sidlofsky, S ;
Pritzker, KPH ;
Hartwick, RW ;
Hanna, W ;
Lickley, L ;
Wilkinson, R ;
Qizilbash, A ;
Ambus, U ;
Lipa, M ;
Weizel, H ;
Katz, A ;
Baida, M ;
Mariz, S ;
Stoik, G ;
Dacamara, P ;
Strongitharm, D ;
Geddie, W ;
McCready, D .
JOURNAL OF CLINICAL ONCOLOGY, 1998, 16 (04) :1340-1349
[3]  
Bacci G, 1997, CANCER-AM CANCER SOC, V79, P245
[4]   EXPRESSION OF P-GLYCOPROTEIN IN HIGH-GRADE OSTEOSARCOMAS IN RELATION TO CLINICAL OUTCOME [J].
BALDINI, N ;
SCOTLANDI, K ;
BARBANTIBRODANO, G ;
MANARA, MC ;
MAURICI, D ;
BACCI, G ;
BERTONI, F ;
PICCI, P ;
SOTTILI, S ;
CAMPANACCI, M ;
SERRA, M .
NEW ENGLAND JOURNAL OF MEDICINE, 1995, 333 (21) :1380-1385
[5]   Phase II study of weekly intravenous recombinant humanized Anti-p185(HER2) monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast [J].
Baselga, J ;
Tripathy, D ;
Mendelsohn, J ;
Baughman, S ;
Benz, CC ;
Dantis, L ;
Sklarin, NT ;
Seidman, AD ;
Hudis, CA ;
Moore, J ;
Rosen, PP ;
Twaddell, T ;
Henderson, IC ;
Norton, L .
JOURNAL OF CLINICAL ONCOLOGY, 1996, 14 (03) :737-744
[6]   Tumor size and prognosis in aggressively treated osteosarcoma [J].
Bieling, P ;
Rehan, N ;
Winkler, P ;
Helmke, K ;
Maas, R ;
Fuchs, N ;
Bielack, S ;
Heise, U ;
Jurgens, H ;
Treuner, J ;
Romanowski, R ;
Exner, U ;
Kotz, R ;
Winkler, K .
JOURNAL OF CLINICAL ONCOLOGY, 1996, 14 (03) :848-858
[7]   P-glycoprotein expression: Critical determinant in the response to osteosarcoma chemotherapy [J].
Chan, HSL ;
Grogan, TM ;
Haddad, G ;
DeBoer, G ;
Ling, V .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1997, 89 (22) :1706-1715
[8]  
CordonCardo C, 1997, SEMIN SURG ONCOL, V13, P319, DOI 10.1002/(SICI)1098-2388(199709/10)13:5<319::AID-SSU5>3.0.CO
[9]  
2-G
[10]   Treatment of metastatic osteosarcoma at diagnosis: A pediatric oncology group study [J].
Harris, MB ;
Gieser, P ;
Goorin, AM ;
Ayala, A ;
Shochat, SJ ;
Ferguson, WS ;
Holbrook, T ;
Link, MP .
JOURNAL OF CLINICAL ONCOLOGY, 1998, 16 (11) :3641-3648