Combined measurement of the c‐erbb‐2 protein in breast carcinoma tissues and sera is useful as a sensitive tumor marker for monitoring tumor relapse

• Published in: International journal of cancer 2000-07, Vol.89 (4), p.329-336
• Main Authors: Sugano, Kokichi, Ushiama, Mineko, Fukutomi, Takashi, Tsuda, Hitoshi, Kitoh, Takashi, Ohkura, Hisanao
• Format: Article
• Language: English
• Subjects: Antigens, Tumor-Associated, Carbohydrate - blood; Antigens, Tumor-Associated, Carbohydrate - metabolism; Biological and medical sciences; Biomarkers, Tumor - blood; Biomarkers, Tumor - metabolism; Breast Neoplasms - blood; Breast Neoplasms - metabolism; Breast Neoplasms - surgery; c-erbB-2 gene; Carcinoembryonic Antigen - blood; Carcinoembryonic Antigen - metabolism; Carcinoma - blood; Carcinoma - metabolism; Carcinoma - surgery; Female; Gynecology. Andrology. Obstetrics; Humans; Mammary gland diseases; Medical sciences; Middle Aged; Mucin-1 - blood; Mucin-1 - metabolism; Neoplasm Recurrence, Local - blood; Neoplasm Recurrence, Local - metabolism; Receptor, ErbB-2 - blood; Receptor, ErbB-2 - metabolism; Retrospective Studies; ROC Curve; Sensitivity and Specificity; Tumors
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/1097-0215(20000720)89:4<329::AID-IJC3>3.0.CO;2-P

c‐erbB‐2 protein levels in tissue extracts and sera were determined in a retrospective analysis of 158 patients who underwent surgical resection of breast carcinoma by means of a sandwich enzyme immunometric assay (EIA) using monoclonal antibodies (MAbs) directed to the extracellular domain of the c‐erbB‐2 oncogene protein (ErbB‐2). In the analysis of tissue extracts, 48 samples (30.3%) showed ErbB‐2 levels exceeding 18.0 ng/mg protein (group A), while in 110 samples these levels were below 18.0 ng/mg protein (group B). Immunohistochemical examination of resected tissues using anti‐c‐erbB‐2 antibody revealed positive staining in 93.8% (45/48) in group A and 13.6% (15/110) in group B (p < 0.00001). The proportion of patients who preoperatively showed a serum ErbB‐2 value above 5.4 ng/ml was 52.1% (25/48) in group A and 10.0% (11/110) in group B (p < 0.00001). Thus, the level of ErbB‐2 in tissue extracts was significantly associated with immunohistochemistry and ErbB‐2 levels in preoperative sera. During follow‐up, 48 patients (30.3%) developed recurrent disease: 17 in group A (35.4%) and 31 in group B (28.2%). From an ROC analysis based on the postoperative serum ErbB‐2 levels in patients either with or without relapse, the cutoff value of serum ErbB‐2 for tumor relapse was determined to be 6.5 ng/ml. The sensitivity of serum ErbB‐2 in patients with relapsed breast cancer was 58.3% (21/36) overall, 84.6% (11/13) in group A and 43.5% (10/23) in group B. In the analysis of serum samples taken before relapse, 90.9% (10/11) of the subjects in group A and 26.7% (4/15) of those in group B were shown to be positive for serum ErbB‐2. Serum ErbB‐2 in group A was a more sensitive marker than other tumor markers such as CEA, CA15‐3, and NCC‐ST‐439. Thus, the determination of ErbB‐2 in tissue extracts of breast carcinoma may be useful for assessing c‐erbB‐2 protein expression in the primary tissue and indicates that serum ErbB‐2 may be a sensitive marker for monitoring tumor relapse. Int. J. Cancer 89:329–336, 2000. © 2000 Wiley‐Liss, Inc.