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Prognostic Utility of Serum -N-Acetylgalactosaminidase and Immunosuppression Resulted from Deglycosylation of Serum Gc Protein in Oral Cancer Patients¹

Laboratory of Cancer Immunology and Molecular Biology, Albert Einstein Cancer Center, Philadelphia, Pennsylvania 19141, [N. Y., V. R. N.], and Department of Oral Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo 663, Japan [M. U.]

Vitamin D₃-binding protein (Gc protein), a serum glycoprotein, is the precursor for the macrophage activating factor. Cancer patient sera contain -N-acetylgalactosaminidase that deglycosylates Gc protein. Deglycosylated Gc protein cannot be converted to macrophage activating factor, leading to immunosuppression. Of 46 oral cancer patients with squamous cell carcinoma, approximately 22% had greatly reduced precursor activities. The precursor activity of approximately 61% of these patients was moderately reduced. The remaining patients (17%) had precursor activities equivalent to those of healthy humans. Patients with low precursor activity of serum Gc protein had high serum -N-acetylgalactosaminidase activity. In contrast, patients with high precursor activity had low serum -N-acetylgalactosaminidase activity. Thus, levels of serum -N-acetylgalactosaminidase of individual patients have an inverse correlation with precursor activities of their serum Gc protein. Surgical removal of tumors resulted in a subtle decrease in serum -N-acetylgalactosaminidase activity with concomitant increase in the precursor activity of serum Gc protein. Serum enzyme analysis of nude mice transplanted with a human oral squamous carcinoma cell line revealed that serum -N-acetylgalactosaminidase activity is directly proportional to tumor burden. Thus, -N-acetylgalactosaminidase activity in patient blood-stream can serve as a diagnostic/prognostic index.

¹ This study was supported by United States Public Health Service Grant AI-32140 (to N. Y.).

² To whom requests for reprints should be addressed, at the Laboratory of Cancer Immunology, Albert Einstein Cancer Center, Korman Research Pavilion B-31, 5501 Old York Road, Philadelphia, PA 19141. Phone: (215) 456-6335; Fax: (215) 456-3824.

Received 8/20/96. Accepted 11/ 8/96.