Meden H, Marx D, Fattahi A, Rath W, Kron M, Wuttke W, Schauer A, Kuhn W
Department of Obstetrics and Gynecology, University of Göttingen, Germany.
J Cancer Res Clin Oncol. 1994;120(6):378-81. doi: 10.1007/BF01247465.
Amplification of the proto-oncogene c-erbB-2 (HER-2/neu) has been shown to be a prognostic marker in ovarian cancer. In order to obtain further information on the biological role of the c-erbB-2 gene product p185 it is necessary to quantify expression levels. In this study we evaluated an enzyme-linked immunosorbent assay (ELISA) for the extracellular domain of p185 to determine whether a soluble oncoprotein fragment can be detected in the serum of ovarian cancer patients and in the serum of pregnant women. Sera from 199 women (57 previously untreated ovarian cancer patients, 62 pregnant women and 80 healthy controls) were assayed in a sandwich ELISA utilizing two mouse monoclonal antibodies. To study c-erbB-2 overexpression in ovarian cancer tissue samples we have used an immunohistochemical technique involving a monoclonal antibody specifically reactive with the external domain of the protein p185. The mean serum value for the normal controls was 1203 HNU/ml with a standard deviation (SD) of 279 HNU/ml and a range of 595-1947 HNU/ml. We chose a level of 1761 HNU/ml (2 SD above the mean) as a cut-off to distinguish individuals with elevated levels. The ovarian cancer patients' serum values ranged from 526 to 16,332 HNU/ml. Immunohistochemically detectable p185 was noted in 8 of 57 ovarian cancer patients. The oncoprotein fragment levels in the sera from these 8 patients ranged from 878 to 16,332 HNU/ml. Of 8 patients with p185 overexpression in their tumors, 4 had elevated serum levels. In the sera from the 49 cancer patients without overexpression the values were distributed in the range 526-2892 HNU/ml. There was no association between serum oncoprotein fragment levels and tumor stage, histological type or grading. Serum concentrations of the p185 fragment in pregnancy ranged from 612 to 3265 HNU/ml. The highest levels were found in the third trimester. The results of the present study raise the possibility that the soluble c-erbB-2 protein level in serum is an indicator for cell proliferation and therefore deserves further evaluation as a diagnostic tool in ovarian cancer patients and pregnancy.
原癌基因c-erbB-2（HER-2/neu）的扩增已被证明是卵巢癌的一个预后标志物。为了获得关于c-erbB-2基因产物p185生物学作用的更多信息，有必要对其表达水平进行定量。在本研究中，我们评估了一种针对p185细胞外结构域的酶联免疫吸附测定（ELISA），以确定在卵巢癌患者血清和孕妇血清中是否能检测到可溶性癌蛋白片段。利用两种小鼠单克隆抗体，采用夹心ELISA法检测了199名女性（57例未经治疗的卵巢癌患者、62名孕妇和80名健康对照）的血清。为了研究卵巢癌组织样本中c-erbB-2的过表达情况，我们采用了一种免疫组织化学技术，该技术使用一种与蛋白p185外部结构域特异性反应的单克隆抗体。正常对照的血清平均值为1203 HNU/ml，标准差（SD）为279 HNU/ml，范围为595 - 1947 HNU/ml。我们选择1761 HNU/ml（高于平均值2个标准差）作为区分水平升高个体的临界值。卵巢癌患者的血清值范围为526至16332 HNU/ml。57例卵巢癌患者中有8例免疫组织化学检测到p185。这8例患者血清中的癌蛋白片段水平范围为878至16332 HNU/ml。在肿瘤中p185过表达的8例患者中，4例血清水平升高。在49例无过表达的癌症患者血清中，值分布在526 - 2892 HNU/ml范围内。血清癌蛋白片段水平与肿瘤分期、组织学类型或分级之间无关联。孕期血清中p185片段的浓度范围为612至3265 HNU/ml。最高水平出现在孕晚期。本研究结果提示，血清中可溶性c-erbB-2蛋白水平可能是细胞增殖的一个指标，因此作为卵巢癌患者和孕期的诊断工具值得进一步评估。
