Most human ovarian
carcinomas express
mesothelin, which is shed as a diagnostically useful
biomarker. We applied an ELISA to measure
antibodies to native
mesothelin in serum from a series of patients with divergent clinical outcomes. The level of anti-
mesothelin antibodies determined as OD(450 nm) and referred to as absorption units (AU) for 1:20 diluted serum was higher in patients who remained disease-free after
therapy [no evidence of disease (NED); n = 14] than in patients whose disease recurred [clinical evidence of disease (CED); n = 21; P < 0.01]. Applying AU > or = 0.5 at a serum dilution of 1:20 as cutoff, 10 of 14 (71%) ovarian
carcinoma patients with NED and 9 of 21 (43%) patients with CED had
antibodies to
mesothelin compared with 6 of 23 (26%) healthy women (P < 0.008) and 5 of 24 (21%) women with other benign
gynecologic diseases (P < 0.003), whereas 7 of 9 (78%) of women with
pelvic inflammatory disease were positive. Three of the 14 (21%) NED patients had circulating
mesothelin detected as an AU > or = 0.2 at a serum dilution of 1:40 (P < 0.005) compared with 15 of 21 (71%) CED patients, and 9 of 14 (64%) NED patients (P < 0.0002) were positive for
antibodies and negative for
antigen compared with 1 of 21 (5%) CED patients. Although our data indicate that an antibody response to
mesothelin is an important correlate of ovarian
carcinoma, prospective studies are needed to show whether the measurement of such
antibodies (alone or together with
antigen)
aids the diagnosis and monitoring of patients.