Placental proteins as tumor markers in human monoclonal gammopathies: results in 109 patients.

Sera from 51 patients with multiple myeloma, 48 patients with monoclonal gammopathy of undetermined significance (MGUS), and 10 patients with Waldenstrom's macroglobulinemia (78 men and 31 women) were analyzed by radioimmunoassay for four placental proteins: the common alpha-subunit of glycoprotein hormones (alpha), chorionic gonadotropin and/or its free beta subunit (CG-beta), placental lactogen (PL), and "pregnancy-specific" beta 1-glycoprotein (SP1), to see if these would be useful tumor markers to distinguish benign from malignant monoclonal gammopathies. The 95th percentiles for serum alpha concentrations in our male patients and normal men were 7.0 and 2.0 ng/ml, respectively. When male patients with renal failure (known to be associated with elevated serum alpha) were excluded, the 95th percentile for serum alpha for the remaining 73 non-uremic men was 4.0 ng/ml. Of these, 7 with MGUS, 2 with macroglobulinemia, and 17 with myeloma had serum alpha concentrations above the 95th percentile for normal men, and analysis of covariance showed that both age and disease category were significantly related to serum alpha concentration. When the serum alpha concentrations from our 73 non-uremic men and 119 normal men were pooled, the 90th percentile was 2.7 ng/ml, and 16 of the 19 individuals in the top 10th percentile came from our non-uremic men (p less than 0.00002). For serum SP1, analysis of data combining our 109 patients with 93 controls again revealed a disproportionate number of the top 10% in our patient population. The 95th percentiles for serum alpha in our female patients, and for serum CG-beta in both sexes, were not significantly elevated above controls. Serum PL concentrations exceeded the 95th percentile of normal in only 5% of our patients, and were not further analyzed. Serum alpha and SP1 concentrations, but not those of CG-beta or PL, were significantly higher for our patients than for controls. These placental proteins are unlikely to be generally useful as tumor markers for monoclonal gammopathies, however, because of the overlap among "benign" and malignant groups, and because of a lack of correlation with stage of the disease as observed in our myeloma patients.