Tumor markers or tumor antigens are used for the monitoring of the response to treatment, follow-up, and potentially for diagnosis and screening. However, use of CA-125 serum assay as a single diagnostic tool. is restricted by the fact that it is also produced by normal epithelia, not only by the ovarian cancer cells. Systemic lupus eryhtematosus (SLE) and related systemic autoimmune syndromes are associated with elevation of CA-125. In this group of patients antigen elevation had been tried to be linked with SLE disease activity. Although not found to be related with the disease activity, CA-125 serum levels were found to be related with the presence of nephrotic syndrome in the English literature. Although particularly important, the presence of ascites was not taken into consideration during the statistical analysis of the relationship between CA-125 elevation and nephrotic syndrome in SLE patients. However most of the SLE patients with nephrotic syndrome would have had accompanying ascites secondary to protein loss. Ascites itself could induce elevation in CA-125 serum levels. With this in mind we can hypothesize that the development of ascites was the primary cause for the elevation of CA-125 in SLE patients with nephrotic syndrome rather than the nephrotic syndrome itself. Probably the presence of ascites was the cause of observed relationship. Most likely ascites was a confounding variable biasing the results and statistical analysis. Failure to control for the presence of confounding variables such as ascites might lead to bias in all clinical trials. Otherwise a causative role for nephrotic syndrome in the elevation of serum CA-125 level seems somewhat inconsequential. (c) 2006 Elsevier Ltd. All rights reserved.