Analysis of the expression of human tumor antigens in ovarian cancer tissues

Article type: Research Article

Authors: Ali-Fehmi, Rouba^{a; c;} | Chatterjee, Madhumita^b; | Ionan, Alexei^b | Levin, Nancy K.^b | Arabi, Haitham^a | Bandyopadhyay, Sudeshna^a | Shah, Jay P.^c | Bryant, Christopher S.^c | Hewitt, Stephen M.^d | O'Rand, Michael G.^e | Alekseev, Oleg M.^e | Morris, Robert^c | Munkarah, Adnan^{c; f} | Abrams, Judith^g | Tainsky, Michael A.^{a; b; *}

Affiliations: [a] Department of Pathology, Wayne State University School of Medicine, Detroit, MI 48201, USA | [b] Program in Molecular Biology and Human Genetics, Karmanos Cancer Institute/Wayne State University, 110 E. Warren, Detroit, MI 48201, USA | [c] Division of Gynecologic Oncology, Wayne State University School of Medicine, Harper Professional Office Bldg, 4160 John R., 2nd Floor, Detroit, MI 48201, USA | [d] Tissue Array Research Program, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, NIH, MSC 4605 Bethesda, MD 20892-4605, USA | [e] Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, 27599, USA | [f] Division of Gynecologic Oncology, Henry Ford Health System, Department of Women's Health Services, 2799 W. Grand Boulevard, Detroit, MI 48202, USA (current address) | [g] Barbara Ann Karmanos Cancer Institute and Wayne State University, 428 HWCRC, 4100 John R, Detroit, MI 48201, USA

Correspondence: [*] Corresponding author. Tel.: +1 313 578 4340; Fax: +1 313 832 7294; E-mail: tainskym@karmanos.org.

Note: [1] Both should be considered first authors.

Abstract: Biomarkers for early detection of cancer have great clinical diagnostic potential. Numerous reports have documented the generation of humoral immune responses that are triggered in response to changes in protein expression patterns in tumor tissues and these biomarkers are referred to as tumor associated antigens (TAAs). Using a high-throughput technology, we previously identified 65 proteins as diagnostically useful TAAs by profiling the humoral immune responses in ovarian cancer (OVCA) patients. Here we determined the expression status of some of those TAAs in tissues from OVCA patients. The protein expression patterns of 4 of those 65 antigens, namely NASP, RCAS1, Nijmegen breakage syndrome1 (NBS1) and eIF5A, along with p53 and Her2 (known molecular prognosticators) and two proteins that interact with NBS1, MRE11 and RAD50, were assessed by immunohistochemistry (IHC). NASP and RCAS1 proteins were more frequently expressed in ovarian cancer tissues than with normal ovarian tissue and serous cystadenomas and MRE11 was less frequently expressed. When evaluated simultaneously, only NASP and MRE11 remained statistically significant with sensitivity of 66% and specificity of 89%. None of these proteins' expression levels were prognostic for survival. Together, our results indicate that occurrence of humoral immune responses against some of these TAAs in OVCA patients is triggered by antigen protein overexpression.

Keywords: Ovarian cancer, phage display, tissue biomarker, humoral immune response, tissue microarray

DOI: 10.3233/CBM-2009-0117

Journal: Cancer Biomarkers, vol. 6, no. 1, pp. 33-48, 2010