beta2-microglobulin in patients with urothelial cancer

beta2-Microglobulin (beta2-mi) is found on the surface of most nucleated cells, and in cancer patients its increased production and liberation into the blood has been described. We studied serum and urinary levels of beta2-mi in 29 patients with urinary bladder cancer (UBC) and 38 patients with upper-tract urothelial cancer (UTUC). A statistically significant (P < 0.01) increase in serum beta2-mi levels was demonstrated in patients with UTUC as compared with controls, whereas urinary excretion of beta2-mi was increased (P < 0.05) in both UTUC and bladder cancer patients. beta2-Mi production was studied in a 72-h culture of peripheral blood mononuclear cells (PBMC) under basal conditions and after stimulation with concanavalin A (Con A) or phytohemagglutinin (PHA). Basal production of beta2-mi by control unstimulated PBMC was 89.3 +/- 5; that of PHA-stimulated PBMC, 189 +/- 22 microg/10(6) cells; and that of Con A-stimulated PBMC, 210 +/- 32 microg/10(6) cells. beta2-Mi production by PBMC of cancer patients was not statistically significantly different from the control value, ruling out the possibility of an increased production by lymphocytes in these patients. Increased production of beta2-mi was demonstrated in 48-h ureteral and urinary bladder-cancer cell cultures, ranging from 440 to 2,600 microg. Serum beta2-mi was found to be increased to values of over 2.7 mg/l in 4 UBC and 12 UTUC patients with normal serum creatinine levels. Tumor surgery in those patients with increased serum beta2-mi resulted in normalization of the serum beta2-mi levels; urinary beta2-mi excretion was not significantly changed by surgery. This study establishes that increased serum levels of beta2-mi found in patients with urothelial cancer and normal glomerular function might be due to the increased production by tumor cells. However, activation of the immune response by mononuclear cells to the neoplasm cannot be excluded.