Pergamon Europron_?oumalofCancerVol. 31A, Nos 13/14, pp. 2239-2242,1995 Ekviu ScienceLtd Printed in Grat Brimin 0959-8049195 $9.50+0.00 Original Paper Alpha-fetoprotein-Concanavalin A Binding as a Marker to Discriminate Between Germ Cell Tumours and Liver Diseases J. Moral, N. Gas&n’, J.M. Tabernero2, J.R. Germh3 and F. GonAlez’ ‘Department of Biochemistry; 2Department of Medical Oncology, Hospital de Sant Pau; and 3Department of Medical Oncology, Hospital Duran i Reynals, Ciutat Sanittia i Universittia de Bellvitge, Barcelona, Spain In order to differentiate whether slight alpha-fetoprotein (AFP) increases observed in any patient are due to germ cell tumours (GCT) or to liver diseases (including hepatotoxicity of chemotherapy), we measured the binding ratio of the AFP to concanavalin A (ConA). A total of 218 serum samples were studied: 102 samples from 72 GCT patients and 116 from patients with liver diseases. Considering a cut-off vahte to be a ConA binding ratio of 15%, we distinguished AFP produced by GCT (> 15%) from AFP produced by tumoral and non-tumoral liver diseases (~15%) with a sensitivity of 98% and specificity of 100%. The difference between mean ConA binding ratios was statistically sign&ant (P < 0.0001). We did not distinguish AFP produced by tumoral and non-tumoral liver diseases. ConA binding ratio may be a sensitive index to distinguish whether an increase of AFP concentration as low as 15 U/ml in a GCT patient during the follow-up is produced by the tumour or by liver dysfunction (including hepatotoxicity of chemotherapy). Key words: alpha-fetoprotein, concanavalin A, germ cell tumours, non-tumoral liver diseases EurJ Cancer, Vol. 31A, Nos 13114, pp. 22392242,1995 INTRODUCTION ALPHA-FETOPROTEIN (AFP) is widely used in diagnosis, in monitoring therapy and in follow-up of patients with germ cell tumours (GCT) and hepatocellular carcinoma. As has been reported previously, an increase in AFP concentration in the follow-up of patients with GCT is difficult to interpret due to the fact that AFP may also rise in non-tumoral diseases of the liver [l-3]. Concanavalin A (ConA)-Sepharose is a lectin that allows the separation of AFP molecular variants according to their carbohydrate moiety. The yolk-sac type of AFP has an additional N-acetylglucosamine linked to the B-mannose that blocks the ConA binding site on AFP[4]. Therefore, if we measure the non- bound AFP fraction to ConA-Sepharose, the yolk-sac type of AFP shows a higher percentage than the liver type. The aim of this study was to determine the ConA binding ratio in patients with GCT and in patients with liver diseases (tumoral and non-tumoral) in order to differentiate between AFP increases produced by malignancies and those due to non- Correspondenceto J. Mora at the Deparmxent of Biochemistry, Hospital de Sant Pau, Avda. Pare Claret 167,08025 Barcelona, Spain. Revised 11 Jul. 1995; accepted 17 Aug. 1995. tumoral liver activity, including hepatotoxicity of chemo- therapy. Patients PATIENTS AND METHODS We analysed a total of 218 serum samples with an AFP concentration above the reference range (59 U/ml). One hun- dred and two samples were obtained from 72 patients with non- seminomatous GCT, treated with cisplatin-based chemotherapy (66 testicular tumours, 3 mediastinal tumours, 1 retroperitoneal tumour and 2 ovarian tumours; Group 1). In 12 of these patients, we determined the AFP-ConA binding ratio serially during the course of treatment with a median of six determinations per patient (range = 2-7). Moreover, we analysed 66 patients with non-tumoral liver diseases (38 hepatocirrhosis, 23 chronic hepa- titis, 3 acute viral hepatitis and 2 alcoholic hepatitis) (Group 2), 45 patients with hepatocellular carcinoma (Group 3) and 5 patients with non-germ cell hepatic metastases (Group 4). Lyphocheck@ (Bio-Bad, ECS Div., Anaheim, California, U.S.A.) was used as control sera in order to evaluate the reproducibility intra- and interserial of the AFP-ConA binding method. 2239