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Clinical significance of the quantitative assessment of the cytosolic concentration of HER-2/neu protein in breast cancer by immunoenzymatic assay (ELISA)

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Abstract

Purpose: Retrospective analysis to assess the prognostic and predictive value of HER-2/ neu expression in breast tumors, quantified by enzyme immunoassay (ELISA).Methods: Quantification of HER-2/neu was performed on cytosolic extracts from 914 cases of primary invasive breast carcinomas. Relapse-free and overall survival data were available from 889 patients. The prognostic value of HER-2/neu levels was assessed considering them as a continuous, dichotomic or quartile variable.Results: Cytosolic HER-2/neu levels ranged widely in breast carcinomas (median: 746.5 NHU/mg; range: 2.8–80,000 NHU/mg protein). HER-2/neu protein levels were significantly higher in either moderately or poorly differentiated tumors, as well as in those showing a ductal histological type, aneuploidy or a high S-phase fraction. There was a significant and positive association between cytosolic and membranous HER-2/neu levels (n=162, r sub S=0.53; P<0.0001). In addition, cytosolic HER-2/neu level correlated weakly with progesterone receptors but not with estrogen receptors. Elevated cytosolic HER-2/neu levels (≥1,400 NHU/mg protein) were associated with a high probability of both shortened relapse-free survival and overall survival. This same cut-off value was obtained when we divided the overall group of patients in a training set. However, this HER-2/neu value did not achieve any statistical significance in a validation set used to make sure that the cut-off was correct. Nevertheless, when we divided the obtained data into three different groups with respect to the quartile values (Q) of the intratumoral oncoprotein levels (≤ Q 1 vs Q 1−Q 2 vs > Q 3), we observed that patients with either low HER-2/ neu levels (≤ Q 1) or high HER-2/neu levels (> Q 3) had shorter both relapse-free survival and overall survival curves than those patients with intermediate HER-2/neu levels. On the other hand, high HER-2/neu levels predicted a poor response to adjuvant chemotherapy but not to adjuvant hormonal therapy with tamoxifen.Conclusions: The results of the present investigation indicate that by quantitatively determining the content of HER-2/neu oncoprotein, groups of high-risk breast cancer patients could be identified, for a more effective clinical management.

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Acknowledgements

Supported by grants from ISCIII, Red de Centros de Cáncer RTICCC (C03/10) and Obra Social Cajastur.

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Authors and Affiliations

  1. Instituto Universitario de Oncología del Principado de Asturias, Oviedo, Spain

    Maria D. Corte, Julio Vázquez, Juan C. Rodríguez, Luis O. González, Ma Luz Lamelas, Maite Allende, Antonio Fueyo & Francisco J. Vizoso

  2. Unidad de Investigación del Hospital de Jove, Gijón, Spain

    Maria D. Corte, Juan A. Rodil, Julio Vázquez, Juan C. Rodríguez, Luis O. González, Ma Luz Lamelas & Francisco J. Vizoso

  3. Servicio de Ginecología, Hospital de Jove, Gijón, Spain

    Julio Vázquez & Ma Luz Lamelas

  4. Servicio de Medicina Nuclear, Hospital Central de Asturias, Oviedo, Spain

    Lucia García & Maite Allende

  5. Servicio de Cirugía General, Hospital de Jove, Avda. Eduardo Castro s/n, 33920, Gijón, Asturias, spain

    Juan C. Rodríguez, Miguel Bongera & Francisco J. Vizoso

  6. Servicio de Cirugía General, Hospital Central de Asturias, Oviedo, Spain

    José C. Fernández & José L. García-Muñiz

  7. Servicio de Anatomía Patológica, Hospital de Jove, Gijón, Spain

    Luis O. González

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Correspondence to Francisco J. Vizoso.

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Corte, M.D., Rodil, J.A., Vázquez, J. et al. Clinical significance of the quantitative assessment of the cytosolic concentration of HER-2/neu protein in breast cancer by immunoenzymatic assay (ELISA). J Cancer Res Clin Oncol 131, 701–714 (2005). https://doi.org/10.1007/s00432-005-0022-3

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