DETECTION OF INCREASED AMOUNTS OF THE EXTRACELLULAR DOMAIN OF THE C-ERBB-2 ONCOPROTEIN IN SERUM DURING PULMONARY CARCINOGENESIS IN HUMANS

Over-expression of the c-erbB-2 oncogene-encoded p185 protein product has been implicated in the pathogenesis of a wide variety of human mal ignancies, including lung cancer. Over-expression of p185 can be detec ted immunologically by quantification of the extracellular domain of p 185 (c-erbB-2 oncopeptide) in extracellular fluid in vitro and in seru m in vivo. An enzyme-linked immunosorbent assay (ELISA) for the c-erbB -2 oncopeptide was used to examine banked serum samples of 11 pneumoco niosis patients who subsequently developed lung cancer and serum sampl es from 11 hospital controls matched for age, sex, ethnic group and sm oking as well as 55 unmatched general population controls. The mean se rum level for the c-erbB-2 oncopeptide in human neu units/ml in the lu ng cancer cases (1,756 +/- 549 HNU/ml) was statistically significantly elevated (p < 0.001) in comparison to the mean level in the matched c ontrols (976 +/- 488 HNU/ml) or the general population controls (888 /- 655 HNU/ml). Defining a positive elevation of the serum c-erbB-2 on copeptide 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 p ositive 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-p ositive cancer cases had positive serum samples prior to the time of d isease diagnosis (average = 35 months). These results suggest that ser um c-erbB-2 oncopeptide may be elevated at an early stage of pulmonary carcinogenesis and that further prospective study of the utility of t his biomarker is warranted. (C) 1994 Wiley-Liss, Inc.