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.
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.
Sugano
K
K
Division of Clinical Laboratory, National Cancer Center Hospital, Tokyo, Japan. ksugano@tcc.pref.tochigi.jp
Ushiama
M
M
Fukutomi
T
T
Tsuda
H
H
Kitoh
T
T
Ohkura
H
H
D015295:Antigens, Tumor-Associated, Carbohydrate / Q000097:blood / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism*; D001943:Breast Neoplasms / Q000097:blood / Q000378:metabolism* / Q000601:surgery; D002272:Carcinoembryonic Antigen / Q000097:blood / Q000378:metabolism; D002277:Carcinoma / Q000097:blood / Q000378:metabolism* / Q000601:surgery; D005260:Female; D006801:Humans; D008875:Middle Aged; D018396:Mucin-1 / Q000097:blood / Q000378:metabolism; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000378:metabolism*; D012372:ROC Curve; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood / Q000378:metabolism*; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D018396:Mucin-1; D018719:Erb-b2 Receptor Tyrosine Kinases; C056315:ST 439 antigen, human