Serum levels of alpha1-antitrypsin isoforms in patients with ovarian clear cell carcinoma: An exploratory study

Background: Ovarian clear cell carcinoma (OCCC) is frequently associated with endometriosis. Since serum levels of cancer antigen 125 (CA125) have limited diagnostic and prognostic value in this malignancy, there is an unmet need for reliable and specific biomarkers. Previous findings indicated that alpha 1-antitrypsin isoforms (isoAAT) are significantly increased in the peritoneal fluid of patients with endometriosis. This study was undertaken to examine whether serum isoAAT levels in patients with OCCC differ from those measured in women with endometriosis or benign ovarian tumors. We also investigated whether this biomarker may be useful for predicting survival in OCCC. Methods: Paired serum samples before and after debulking surgery were collected from 27 patients with OCCC. All sera from patients with endometriosis (n = 44) and benign ovarian tumors (n = 32) were obtained in the pretreatment phase. Serum isoAAT levels were assayed using a proprietary ELISA kit. Results: The highest levels of serum isoAAT (median, range) were identified in patients with OCCC (preoperative values: 160.9 ng/mL, range, 101.4-1098.8 ng/mL), followed by patients with endometriosis (125.0 and 83.4-473.2 ng/mL), and those with benign tumors (125.2 and 60.5-191.3 ng/mL). The differences in serum isoAAT levels between patients with OCCC and benign tumors were significant (p = 0.041). Debulking surgery of OCCC resulted in a significant decrease in serum isoAAT levels compared with the preoperative period (median, 160.9 versus 113.0 ng/mL, respectively, p = 0.012). As for prognostic prediction, we found that none of the nine patients with OCCC and serum isoAAT levels ≤130 ng/mL died of disease. Conclusion: Serum isoAAT levels may be diagnostically useful to distinguish OCCC from benign ovarian tumors and could also serve as a potential prognostic marker.