Germ cell tumor (GCT) is one of the few malignancies in which recurrent patients would have a good chance of cure by chemotherapy. Using semiquantitative reverse transcription polymerase chain reaction for alpha-fetoprotein (alphafp) mRNA, we measured the circulating tumor load in 54 peripheral blood samples from 7 GCT patients at diagnosis and 47 healthy controls. Clinicopathological information of GCT patients was obtained during a 12-month follow-up. As compared to the upper limit among healthy controls, alphafp mRNA levels increased 23-3.4x103-fold pre-treatment in all 7 patients, and 2.8x103-1.4x104-fold post-treatment in 2 patients studied. All 7 patients with substantially elevated alphafp mRNA levels developed recurrence or metastasis within 12 months of diagnosis. We present evidence that alphafp-expressing tumor cells disseminating in GCT patients before treatment may possibly be the source of recurrence or metastasis. Sequential quantification of alphafp mRNA during the clinical course may provide crucial information for identifying GCT patients at high risk for metastasis.

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