Cancer testis antigen OY-TES-1: analysis of protein expression in ovarian cancer with tissue microarrays

Objectives: The purpose of this study was to determine the potential of cancer testis antigen OY-TES-1 as a vaccine for ovarian cancer (OC). Materials and Methods: A tissue microarray (TMA) containing 107 samples from OC tissues and 48 samples from OC adjacent tissues was analyzed by immunohistochemistry with the OY-TES-1 polyclonal antibody. The correlation between OY-TES-1 and clinic pathological traits of OC was statistically analyzed. Results: The expression of OY-TES-1 protein was found in 81% (87/107) of OC tissues and 56% (27/48) of OC adjacent tissues. The immunostaining intensity of OY-TES-1 in OC tissues was significantly higher than that in OC adjacent tissues tested (p = 0.040). OC adjacent tissues only demonstrated lower immunostaining intensity, whereas some of OC tissues presented higher immunostaining intensity and majority showed the heterogeneity of protein distribution. There was nostatistically significant correlation found between OY-TES-1 expression and any other clinicopathological traits such as age, FIGO stage, pathological grade, and histological type. Conclusions: OY-TES-1 was expressed in OC tissues with a high proportion, and some of OC tissues presented OY-TES-1 expression in high level vs OC adjacent tissues. OY-TES-1 could be an attractive target for immunotherapyfor OC in the future.

OY-TES-1 protein; Ovarian cancer; Immunohistochemistry; Antigen; Immunotherapy.

[1] Jemal A., Siegel R., Ward E., Hao Y., Xu J., Thun M.J.: “Cancer statistics, 2009”. CA Cancer J Clin., 2009, 59, 225.

[2] Hudson L.G., Zeineldin R., Stack M.S.: “Phenotypic plasticity of neoplastic ovarian epithelium: unique cadherin profiles in tumor progression”. Clin. Exp. Metastasis, 2008, 25, 643.

[3] Riedinger J.M., Wafflart J., Ricolleau G., Eche N., Larbre H., Basuyau J.P., et al.: “CA 125 half-life and CA 125 nadir during induction chemotherapy are independent predictors of epithelial ovarian cancer outcome: results of a French multicentric study”. Ann Oncol., 2006, 17, 1234.

[4] Sabbatini P.J., Ragupathi G., Hood C., Aghajanian C.A., Juretzka M., Iasonos A., et al.: “Pilot study of a heptavalent vaccine-keyhole limpet hemocyanin conjugate plus QS21 in patients with epithelial ovarian, fallopian tube, or peritoneal cancer”. Clin. Cancer Res., 2007, 13, 4170.

[5] Caballero O.L., Chen Y.T.: “Cancer/testis (CT) antigens: potential targets for immunotherapy”. Cancer Sci., 2009, 100, 2014.

[6] Smith H.A., McNeel D.G.: “The SSX family of cancer-testis antigens as target proteins for tumor therapy”. Clin. Dev. Immunol., 2010, 2010, 150591. doi: 10.1155/2010/150591. Epub 2010 Oct 11.

[7] Tsuji T., Altorki N.K., Ritter G., Old L.J., Gnjatic S.: “Characterization of preexisting MAGE-A3-specific CD4+ T cells in cancer patients and healthy individuals and their activation by protein vaccination”. J. Immunol., 2009, 183, 4800.

[8] Ono T., Kurashige T., Harada N., Ono T., Noguchi Y., Saika T., Niikawa N., et al.: “Identification of proacrosin binding protein sp32 precursor as a human cancer/testis antigen”. Proc. Natl. Acad. Sci. U. S. A., 2001, 98, 3282.

[9] Baba T., Niida Y., Michikawa Y., Kashiwabara S., Kodaira K., Takenaka M., et al.: “An acrosomal protein, sp32, in mammalian sperm is a binding protein specific for two proacrosins and an acrosin intermediate”. J. Biol. Chem., 1994, 269, 10133.

[10] Tammela J., Uenaka A., Ono T., Noguchi Y., Jungbluth A.A., Mhawech-Fauceglia P., et al.: “OY-TES-1 expression and serum immunoreactivity in epithelial ovarian cancer”. Int. J. Oncol., 2006, 29, 903.

[11] Serov S., Scully R.E.: “International histological classification of tumors No. 9, in Histological typing of ovarian tumors”. Geneva: World Health Organization, 1973, 51. Available at: http://apps.who.int/iris/ bitstream/10665/41529/1/a28749_eng.pdf

[12] Luo B., Yun X., Fan R., Lin Y.D., He S.J., Zhang Q.M.: “Cancer testis antigen OY-TES-1 expression and serum immunogenicity in colorectal cancer: its relationship to clinicopathological parameters”. Int. J. Clin. Exp. Pathol., 2013, 6, 2835.

[13] Scanlan M.J., Simpson A.J., Old L.J.: “The cancer/testis genes: review, standardization, and commentary”. Cancer Immun., 2004, 4, 1.

[14] Garg M., Chaurasiya D., Rana R., Jagadish N., Kanojia D., Dudha N., et al.: “Sperm-associated antigen 9, a novel cancer testis antigen, is a potential target for immunotherapy in epithelial ovarian cancer”. Clin. Cancer Res., 2007, 13, 1421.

[15] Chiriva-Internati M., Weidanz J.A., Yu Y., Frezza E.E., Jenkins M.R., Kennedy R.C., et al.: “Sperm protein 17 is a suitable target for adoptive T-cell-based immunotherapy in human ovarian cancer”. J. Immunother., 2008, 31, 693.

[16] Chen Y.T., Hsu M., Lee P., Shin S.J., Mhawech-Fauceglia P., Odunsi K., et al.: “Cancer/testis antigen CT45: analysis of mRNA and protein expression in human cancer”. Int. J. Cancer, 2009, 124, 2893.

[17] Yakirevich E., Sabo E., Lavie O., Mazareb S., Spagnoli G.C., Resnick M.B.: “Expression of the MAGE-A4 and NY-ESO-1 cancer-testis antigens in serous ovarian neoplasms”. Clin. Cancer Res., 2003, 9, 6453.

[18] Tammela J., Jungbluth A.A., Qian F., Santiago D., Scanlan M.J., Keitz B., et al.: “SCP-1 cancer/testis antigen is a prognostic indicator and a candidate target for immunotherapy in epithelial ovarian cancer”. Cancer Immun., 2004, 4, 10.

[19] Hasegawa K., Koizumi F., Noguchi Y., Hongo A., Mizutani Y., Kodama J., et al.: “SSX expression in gynecological cancers and antibody response in patients”. Cancer Immun., 2004, 4, 16.

[20] Diefenbach C.S., Gnjatic S., Sabbatini P., Aghajanian C., Hensley M.L., Spriggs D.R., et al.: “Safety and immunogenicity study of NYESO- 1b peptide and montanide ISA-51 vaccination of patients with epithelial ovarian cancer in high-risk first remission”. Clin. Cancer Res., 2008, 14, 2740.

[21] Odunsi K., Qian F., Matsuzaki J., Mhawech-Fauceglia P., Andrews C., Hoffman E.W., et al.: “Vaccination with an NY-ESO-1 peptide of HLA class I/II specificities induces integrated humoral and T cell responses in ovarian cancer”. Proc. Natl. Acad. Sci. U. S. A., 2007, 104, 2837.

[22] Wischnewski F., Pantel K., Schwarzenbach H.: “Promoter demethylation and histone acetylation mediate gene expression of MAGEA1, -A2, -A3, and -A12 in human cancer cells”. Mol. Cancer Res., 2006, 4, 339.

[23] Whitehurst A.W., Xie Y., Purinton S.C., Cappell K.M., Swanik J.T., Larson B., et al.: “Tumor antigen acrosin binding protein normalizes mitotic spindle function to promote cancer cell proliferation”. Cancer Res., 2010, 70, 7652.

[24] Okumura H., Noguchi Y., Uenaka A., Aji T., Ono T., Nakagawa K., et al.: “Identification of an HLA-A24-restricted OY-TES-1 epitope recognized by cytotoxic T-cells”. Microbiol. Immunol., 2005, 49, 1009.