Clinical relevance of alphafetoprotein microheterogeneity in alphafetoprotein-secreting tumors

The importance of the oncofetal glycoprotein antigen alphafetoprotein (AFP) as a tumor marker is well documented. Structural heterogeneity of AFP molecules due to its associated carbohydrate moieties has also been demonstrated. In the present study, molecular variants of AFP, Concanavalin A reactive (R Con A) and Concanavalin A nonreactive (NR Con A) were quantified in five cases of hepatocellular carcinoma (HCC), three cases of hepatoblastoma, five gonadal and two extragonadal germ cell tumors, and two suspected liver secondaries by employing crossed immunoaffino electrophoresis (CIAE). AFP peaks were localized using anti-AFP antibodies conjugated to alkaline phosphatase. Characteristic patterns of AFP R Con A and NR Con A fractions were obtained in different AFP-secreting malignancies. Serum samples of HCC and hepatoblastoma were predominantly composed of R Con A AFP, while gonadal and extragonadal germ cell tumors showed significant reduction of R Con A AFP and elevation of NR Con A AFP. Analysis of AFP variants in sera from two patients of suspected liver metastasis with elevated AFP confirmed liver secondaries arising from germ cell tumor in one patient and HCC in the other patient. The present study highlights the importance of AFP microheterogeneity analysis not only as diagnostic aid for the differential diagnosis of AFP-secreting tumors, but also in providing better management and prognosis.