Detection and Quantitation of Serum Mesothelin, a Tumor Marker for Patients with Mesothelioma and Ovarian Cancer

Clinical Cancer Research. Vol. 12, 447-453, January 2006. [Link]

Raffit Hassan¹, Alan T. Remaley², Maureen L. Sampson², Jingli Zhang¹, Derrick D. Cox³, James Pingpank³, Richard Alexander³, Mark Willingham⁴, Ira Pastan¹ and Masanori Onda¹

Authors’ Affiliations: ¹ Laboratory of Molecular Biology, ² Department of Laboratory Medicine, and ³ Surgery Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland; and ⁴ Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, North Carolina

Requests for reprints: Raffit Hassan, Laboratory of Molecular Biology, National Cancer Institute, 37 Convent Drive, Room 5116, Bethesda, MD 20892-4264. Phone: 301-451-8742; Fax: 301-402-1344; E-mail: hassanr@mail.nih.gov.

Abstract

Purpose: To determine whether mesothelin, a cell surface protein highly expressed in mesothelioma and ovarian cancer, is shed into serum and if so to accurately measure it.

Experimental Design: We developed a sandwich ELISA using antibodies reacting with two different epitopes on human mesothelin. To quantitate serum mesothelin levels, a standard curve was generated using a mesothelin-Fc fusion protein. Sera from 24 healthy volunteers, 95 random hospital patients, 56 patients with mesothelioma, and 21 patients with ovarian cancer were analyzed. Serum mesothelin levels were also measured before and after surgical cytoreduction in six patients with peritoneal mesothelioma.

Results: Elevated serum mesothelin levels were noted in 40 of 56 (71%) patients with mesothelioma and in 14 of 21 (67%) patients with ovarian cancer. Serum mesothelin levels were increased in 80% and 75% of the cases of mesothelioma and ovarian cancer, respectively, in which the tumors expressed mesothelin by immunohistochemistry. Out of the six patients with peritoneal mesothelioma who underwent surgery, four had elevated serum mesothelin levels before surgery. Out of these four patients, three had cytoreductive surgery and the serum mesothelin level decreased by 71% on postoperative day 1 and was undetectable by postoperative day 7.

Conclusions: We developed a serum mesothelin assay that shows that mesothelin is elevated in patients with mesothelioma and ovarian cancer. The rapid decrease in mesothelin levels after surgery in patients with peritoneal mesothelioma suggests that serum mesothelin may be a useful test to monitor treatment response in mesothelin-expressing cancers.