title: Detection of increased amounts of the extracellular domain of the c-erbB-2 oncoprotein in serum during pulmonary carcinogenesis in humans.
abstract: Over-expression of the c-erbB-2 oncogene-encoded p185 protein product has been implicated in the pathogenesis of a wide variety of human malignancies, including lung cancer. Over-expression of p185 can be detected immunologically by quantification of the extracellular domain of p185 (c-erbB-2 oncopeptide) in extracellular fluid in vitro and in serum in vivo. An enzyme-linked immunosorbent assay (ELISA) for the c-erbB-2 oncopeptide was used to examine banked serum samples of 11 pneumoconiosis patients who subsequently developed lung cancer and serum samples from 11 hospital controls matched for age, sex, ethnic group and smoking as well as 55 unmatched general population controls. The mean serum level for the c-erbB-2 oncopeptide in human neu units/ml in the lung cancer cases (1,756 +/- 549 HNU/ml) was statistically significantly elevated (p < 0.001) in comparison to the mean level in the matched controls (976 +/- 488 HNU/ml) or the general population controls (888 +/- 655 HNU/ml). Defining a positive elevation of the serum c-erbB-2 oncopeptide as any value more than 2 standard deviations above the mean of the matched controls, 64% (7 of 11) of the lung cancer cases were positive compared to 0% (0 of 11) matched controls and 5% (3 of 55) of the unmatched controls. In addition, 4 of the 7 c-erbB-2 oncopeptide-positive cancer cases had positive serum samples prior to the time of disease diagnosis (average = 35 months). These results suggest that serum c-erbB-2 oncopeptide may be elevated at an early stage of pulmonary carcinogenesis and that further prospective study of the utility of this biomarker is warranted.
authors.affiliation: Department of Medicine, Columbia University, New York, NY 10032.
authors.forename: P W
authors.initials: PW
authors.lastname: Brandt-Rauf
authors.forename: J C
authors.initials: JC
authors.lastname: Luo
authors.forename: W P
authors.initials: WP
authors.lastname: Carney
authors.forename: S
authors.initials: S
authors.lastname: Smith
authors.forename: I
authors.initials: I
authors.lastname: De Vivo
authors.forename: C
authors.initials: C
authors.lastname: Milling
authors.forename: K
authors.initials: K
authors.lastname: Hemminki
authors.forename: H
authors.initials: H
authors.lastname: Koskinen
authors.forename: H
authors.initials: H
authors.lastname: Vainio
authors.forename: A I
authors.initials: AI
authors.lastname: Neugut
mesh_terms: D000368:Aged; D001195:Asbestosis / Q000150:complications; D014408:Biomarkers, Tumor / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D066246:ErbB Receptors / Q000097:blood*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000097:blood*; D018719:Erb-b2 Receptor Tyrosine Kinases; D012016:Reference Values; D012307:Risk Factors; D012829:Silicosis / Q000150:complications
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases