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

Richard Gorlick, Andrew G. Huvos, Glenn Heller, Alex Aledo, G. Peter Beardsley, John H. Healey, Paul A. Meyers

Research output: Contribution to journalArticle

249 Citations (Scopus)

Abstract

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 was 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.

Original languageEnglish (US)
Pages (from-to)2781-2788
Number of pages8
JournalJournal of Clinical Oncology
Volume17
Issue number9
StatePublished - Sep 1999
Externally publishedYes

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Osteosarcoma
Survival
Disease-Free Survival
Glycoproteins
Monoclonal Antibodies
Biopsy
Drug Therapy
San Francisco
human ERBB2 protein
Paraffin
Retrospective Studies
Clinical Trials
Recurrence
Antibodies

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Gorlick, R., Huvos, A. G., Heller, G., Aledo, A., Beardsley, G. P., Healey, J. H., & Meyers, P. A. (1999). Expression of HER2/erbB-2 correlates with survival in osteosarcoma. Journal of Clinical Oncology, 17(9), 2781-2788.

Expression of HER2/erbB-2 correlates with survival in osteosarcoma. / Gorlick, Richard; Huvos, Andrew G.; Heller, Glenn; Aledo, Alex; Beardsley, G. Peter; Healey, John H.; Meyers, Paul A.

In: Journal of Clinical Oncology, Vol. 17, No. 9, 09.1999, p. 2781-2788.

Research output: Contribution to journalArticle

Gorlick, R, Huvos, AG, Heller, G, Aledo, A, Beardsley, GP, Healey, JH & Meyers, PA 1999, 'Expression of HER2/erbB-2 correlates with survival in osteosarcoma', Journal of Clinical Oncology, vol. 17, no. 9, pp. 2781-2788.
Gorlick R, Huvos AG, Heller G, Aledo A, Beardsley GP, Healey JH et al. Expression of HER2/erbB-2 correlates with survival in osteosarcoma. Journal of Clinical Oncology. 1999 Sep;17(9):2781-2788.
Gorlick, Richard ; Huvos, Andrew G. ; Heller, Glenn ; Aledo, Alex ; Beardsley, G. Peter ; Healey, John H. ; Meyers, Paul A. / Expression of HER2/erbB-2 correlates with survival in osteosarcoma. In: Journal of Clinical Oncology. 1999 ; Vol. 17, No. 9. pp. 2781-2788.
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abstract = "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 was 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.",
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