Biochemical characterization of alpha-fetoprotein and other serum proteins produced by a uterine endometrial adenocarcinoma.

A high serum alpha-fetoprotein (AFP) level was found in a patient with endometrial adenocarcinoma of the uterus, which appeared to be hepatoid on histological examination. The AFP of this unusual patient was purified by immunoaffinity chromatography and characterized. The electrophoretic profiles on sodium dodecyl sulfate-polyacrylamide get electrophoresis both before and after glycopeptidase F treatment were indistinguishable from those of a hepatoma AFP. This indicates that the patient's AFP was also composed of a single polypeptide chain of Mr 67,000 and an N-linked sugar chain of Mr 3,000. Amino acid sequence analyses of this AFP, and of AFP from hepatoma and umbilical cord serum indicated that the N-terminal sequences were essentially the same. The sequence, Arg-Thr-Leu-His-Arg-Asn-Glu-Tyr-Gly-Ile, was slightly different from previous reports, but matched that deduced from the cDNA sequence. AFP isoforms due to microheterogeneity of the sugar chain were analyzed by lectin affinity electrophoresis using a series of lectins. The AFP isoform profiles were distinct from those of proteins derived from cord serum, hepatoma, yolk sac tumor and gastric cancer. The reverse-transcription of RNA from the tumor tissue followed by a polymerase chain reaction using primers with AFP-specific sequences gave a product of the size and nucleotide sequence expected for AFP. mRNAs possessing the requisite sequences for albumin and transferrin syntheses were also detected in the tumor. The expression of these hepatocyte-specific proteins supported the hepatoid nature of this tumor.