Abstract
Concentrations of a fragment of the c-erbB-2 translational product (p185 fragment) were measured in serum of 70 breast cancer patients, 19 healthy blood donors, and 18 pregnant women using a heterogenic enzyme immunoassay. The serum concentrations of blood donors and pregnant women were below 30 kU/l. Breast cancer patients showed serum concentrations up to 578 kU/l. All 9/70 patients with serum concentrations higher than 30 kU/l had clinical evidence of metastatic disease and the serum levels of all 35/70 patients without metastasis lay within the normal range. From 9/37 patients with p185 overexpression of the primary tumor in immunohistochemical analysis 3/9 patients with metastatic disease had elevated serum levels higher than 30 kU/l. In all, 6/9 patients without metastasis serum levels were below 30 kU/l. The data of the present study suggest that determination of serum p185 fragment concentrations may be useful as a diagnostic tool in postoperative follow-up of breast cancer patients with c-erbB-2 overexpression of the primary tumor.
This is a preview of subscription content, log in via an institution to check access.
Abbreviations
- ICA:
-
immunohistochemical analysis
References
Akiyama T, Sudo CH, Ogawara H, Toyoshima K, Yamamoto T (1986) The product of the human c-erbB-2 gene: a 185 kilodalton glycoprotein with tyrosine kinase activity. Science 232:1644–1646
Alper Ö, Yamaguchi K, Hitomi J, Honda S, Matsushima T, Abe K (1990) The presence of c-erbB-2 gene product-related protein in culture medium conditioned by breast cancer cell line SK-BR-3. Cell Growth Differ 1:591–599
Bargmann CI, Hung MC, Weinberg RA (1986) Theneu oncogene encodes an epidermal growth factor-related protein. Nature 319: 226–230
Borg A, Baldetorp B, Fernö M, Killander D, Olsson H, Sigurdsson H (1991) ERBB2 amplification in breast cancer with a high rate of proliferation. Oncogene 6:137–143
Carney WP, Hamer PJ, Petit D, Retos C, Greene R, Zabrecky JR, McKenzie S, Hayes D, Kufe D, DeLellis R, Naber S, Wolfe H (1991) Detection and quantitation of the human neu protein. J Tumor Marker Oncol 6:53–72
Coussens L, Yang-Feng TL, Liao YC, Chen E, Gray A, McGrath J, Seeburg PH, Liberman TA, Schlessinger J, Francke U, Levinson A, Ullrich A (1985) Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location withneu oncogene. Science 230:1132–1139
Fukushige SI, Matsubara KI, Yoshida M, Sasaki M, Suzuki T, Semba K, Toyoshima K, Yamamoto T (1986) Localisation of a novel v-erbB-related gene c-erbB-2 on chromosome 17 and its amplification in a gastric cancer cell line. Mol Cell Biol 6:955–958
Hayes DF, Carney W, Tondini C, Petit D, Henderson C, Kufe DW (1989) Elevated circulating c-neu oncogene product in patients with breast cancer (abstract). 12th Annual San Antonio Breast Cancer Symposium
Isola J, Kallioniemi O-P, Mauceri J, Sampson E, Teramoto Y (1992) Elevated preoperative serum levels of c-erbB-2 antigen in a small group of breast cancer patients with poor survival (abstract). Eighty-third Annual Meeting of the American Association for Cancer Research, San Diego
Kath R, Höffken K, Kummer G, Lümmen G, Scheulen ME, Seeber S (1991) Shedding of the c-neu oncogene product into the serum of patients with breast carcinoma (abstract). Tumor associated antigens, oncogenes, receptors, cytokines in tumor diagnosis and therapy at the beginning of the 90th, Hamburg, December 9–11
Kynast B, Binder L, Marx D, Schmoll HJ, Oellerich M, Schauer A (1992) Bestimmung eines Fragments des c-erbB-2-Translationsproduktes p185 im Serum von Mammakarzinom-Patienten (abstract). Deutsche Gesellschaft für Senologie 12. Wissenschaftliche Tagung, Köln
Lin YZ, Clinton GM (1991) A soluble protein related to the HER-2 proto-oncogene product is released from human breast carcinoma cells. Oncogene 6:639–643
Mitze N, Kreienberg R (1991) Detection of c-erbB-2 oncoprotein immunohistochemically in breast cancer tissue and in sera of women with mammary cancer (abstract). Tumor associated antigens, oncogenes, receptors cytokines in tumor diagnosis and therapy at the beginning of the 90th, December 9–11
Mori S, Mori Y, Mukaiyama T, Yamada Y, Sonobe Y, Matsushima H, Sakamoto G, Akiyama T, Ogawa M, Shiraishi M, Toyoshima K, Yamamoto T (1990) In vitro and in vivo release of solubleerbB-2 protein from human carcinoma cells. Jpn J Cancer Res 81:489–494
Press MF, Cordon-Cardo C, Slamon DJ (1990) Expression of theHER2/neu proto-oncogene in normal human adult and fetal tissues. Oncogene 5:953–962
Schauer A, Marx D, Lipp I, Schumacher M, Sauerbrei W, Rauschecker H, Sauer H (1992) Diagnostic tools and prognostic factors in human breast cancer evaluated by morphological and immunhistochemical methods. In: Dogliotti L, Sapino A, Bussolati G (eds) Breast cancer: Biological and clinical progress. Kluver Academical Publishers (Dordrecht) pp 255–276
Schechter AL, Stern DF, Vaidyanathan L, Decker SJ, Drebin JA, Greene MI, Weinberg RA (1984) Theneu oncogene: anerb-B-related gene encoding a 185,000-M tumor antigen. Nature 312:513–516
Schechter AL, Hung MC, Vaidyanathan L, Weinberg RA, Yang-Feng TL, Francke U, Ullrich A, Coussens L (1985) Theneu gene: anerbB-homologous gene distinct from and unlinked to the encoding EGF receptor. Science 229:974–976
Schimmelpenning H, Eriksson ET, Falkmer UG, Azavedo E, Svane G, Auer GU (1992) Expression of the c-erbB-2 proto-oncogene product and nuclear DNA content in benign and malignant breast parenchyma. Virchows Arch [A] 420:433–440
Schlicker M, Kynast B, Zoll B, Marx D, Fischer G, Rauschecker H-F, Schauer A (1991) Molecular and immunohistochemical investigations of c-erb B2 and p53 in breast cancer (abstract). International Association for Breast Cancer Research. St. Vincenz, Italy
Sias PE, Kotts CE, Vetterlein D, Shepard M, Wong WL (1990) ELISA for quantitation of the extracellular domain of p185HER2 in biological fluids. J Immunol Methods 132:73–80
Slamon DI, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235:177–182
Speiser P, Zeillinger R, Czerwenka K, Kury F, Sliutz G, Knogler W, Kubista E (1991) Detection of c-erbB-2 expression in breast cancer: evaluation of an immunocytochemical assay, a new tissue extract enzyme immuno assay and a serum enzyme immuno assay (abstract). Tumor associated antigens, oncogenes, receptors, cytokines in tumor diagnosis and therapy at the beginning of the 90th, Hamburg December 9–11
Tandon AK, Clark GM, Chamness GC, Ullrich A, McGuire WL (1989)HER-2/neu oncogene protein and prognosis in breast cancer. J Clin Oncol 7:999–1006
Teramoto Y, Walingford S, Mauceri J, Sampson E (1991) Serum enzyme immunoassay kit for the detection of c-erbB-2 oncoprotein (abstract). Eighty-third Annual Meeting of the American Association for Cancer Research, Houston
van de Vijver MJ, Mooi WJ, Wisman P, Peterse JL, Nusse R (1988) Immunohistochemical detection of theneu protein in tissue sections of human breast tumors with amplified neu DNA. Oncogene 2:175–178
Volas G, Leitzel D, Teramoto Y, Sampson EL, Mauceri J, Demers L, Santen R, Harvey H, Mulagha M, Lipton A (1992) Serial serum c-erbB-2 levels and response in breast cancer patients (abstract). Eighty-third Annual Meeting of the American Association for Cancer Research, San Diego
Zabrecky JR, Lam T, McKenzie SJ, Carney W (1991) The extracellular domain of p185/neu is released from the surface of human breast carcinoma cells, SK-BR-3. J Biol Chem 266:1716–1720
Zoll B, Correl B, Kynast B, Fischer G, Marx D, Schauer A (1991) Veränderungen desHER-2 Genes in Mammatumoren. Verh Dtsch Ges Pathol 75:281
Zoll B, Kynast B, Corell B, Marx D, Fischer G, Schauer A (1992) Alterations of the c-erbB-2 gene in human breast cancer. J Cancer Res Clin Oncol 118:468–473
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kynast, B., Binder, L., Marx, D. et al. Determination of a fragment of the c-erbB-2 translational product p185 in serum of breast cancer patients. J Cancer Res Clin Oncol 119, 249–252 (1993). https://doi.org/10.1007/BF01212719
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01212719