GERM-CELL TUMORS EXPRESS A SPECIFIC ALPHA-FETOPROTEIN VARIANT DETECTABLE BY ISOELECTRIC-FOCUSING

Background. Many nonseminomatous germ cell tumors (NSGCTs) express ele vated levels of serum alphafetoprotein (AFP), which is widely used for diagnosis and monitoring therapy. Alpha-fetoprotein is also expressed in patients with hepatocellular carcinoma (HCC). In these sera, sever al variants, some highly specific, recently have been detected by isoe lectric focusing. Methods. Sera were collected from nine patients with NSGCTs, five pregnant women, and five patients with HCC. After isoele ctric focusing, the proteins were transferred to nitrocellulose membra ne by blotting and incubated with polyclonal rabbit antihuman AFP conj ugated with horseradish peroxidase. The enhanced chemiluminescence det ection system and Hyperfilm-ECL were used to render the protein bands visible and each was quantified as a percentage of the total AFP using a densitometer. Results. Isoelectric focusing of serum alpha-fetoprot ein from the patients with NSGCTs (four testicular, five mediastinal) revealed a consistent pattern characterized by a specific band (band III). A second band (band SII) that is also seen in sera from patients with hepatocellular carcinoma was present in all patients. The overal l pattern was distinct from that of AFP from HCC and that produced dur ing late pregnancy. The two characteristic bands (AFP SII and +III) we re responsible for the great majority of total AFP in these patients; estimation of serial sera in patients undergoing treatment showed that total and ''malignant'' AFP changed in parallel. Banding patterns, ap art from one patient, were identical in patients with testicular and m ediastinal NSGCTs. Conclusion. NSGCTs tumors express a highly consiste nt and specific pattern of AFP variants. More detailed analysis of AFP patterns in larger numbers of patients may provide further insight in to the cellular heterogeneity of germ cell tumors.