Sperm-associated Antigen 9 Is a Biomarker for Early Cervical Carcinoma

BACKGROUND: Cervical cancer is the second most common malignancy in women, with nearly half a million new cases diagnosed each year worldwide. The authors' recent studies have suggested an association of the cancer testis antigen sperm-associated antigen 9 (SPAG9) in ovarian carcinomas. The aim of the current study was to evaluate the clinical utility of SPAG9 expression and humoral immune response in cervical carcinomas. METHODS: SPAG9 mRNA expression was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ RNA hybridization. In addition, the authors investigated SPAG9 protein expression by immunohistochemistry and analyzed its association with various stages and grades of cervical cancer patients. They also tested the humoral immune response against SPAG9 in cervical cancer patients. RESULTS: RT-PCR, in situ RNA hybridization, and immunohistochemical analyses revealed that SPAG9 expression was significantly associated with tumor grades in 82% of early stage cervical cancer specimens. SPAG9 antibodies were detected in approximately 80% of cervical cancer patients, but not in healthy controls. Statistical analysis revealed that a significant proportion of early stage cancer patients with a high SPAG9 immunoreactivity score (IRS) exhibited significantly higher antibody response against SPAG9 compared with moderate SPAG9 IRSs, suggesting a close relation between SPAG9 protein expression and humoral immune response. CONCLUSIONS: The current study findings revealed that in early stage cervical cancer, a substantial number of patients exhibited SPAG9 expression and generated SPAG9 antibodies, supporting its potential role in early detection and diagnosis in cervical cancer management. Furthermore, these findings provide leads for future development of noninvasive serologic biomarkers for the early detection, diagnosis, and treatment of cervical cancer. Cancer 2009;115:2671-83. (C) 2009 American Cancer Society.