BORIS, a novel cancer-testis antigen, is a potential target for immunotherapy in epithelial ovarian cancer

Abstract

9673 Background: Cancer-testis antigens (CTA), are selectively expressed in various types of human neoplasms but not in normal tissues other than testis. This characteristic feature of CTA makes them promising targets for cancer-specific immunotherapy. Brother of Regulator Imprinted Sites (BORIS), a novel CTA located on chromosome 20q13.2, is involved in epigenetic re-programming. The aims of this study were to determine the frequency of aberrant expression of BORIS in epithelial ovarian cancer (EOC) and examine its correlation with clinical outcome. Methods: One step RT-PCR was performed with RNA from various normal and 94 EOC tumor tissues obtained from 1995 to 2002. A 270bp BORIS PCR product was amplified using specific sense 5’-CAGGCCCTACAAGTGTAACGACTGCAA and antisense 5’-GCATTCGTAAGGCTTCTCACCTGAGTG primers. Glyceraldehyde-3-phosphodehydrogenase (GAPDH) specific PCR amplification was used as control The χ2 test was used to analyze the distribution of BORIS expression and clinical outcome. Survival distributions were calculated by the Kaplan-Meier method and statistical significance was determined with the log-rank test. Results: Aberrant expression of BORIS was present in (63/ 94) 67% of EOC primary tumors, and undetectable in a panel of 16 normal tissues. The normal ovarian surface epithelial cell lines, IOSE and HOSE were negative for BORIS while 3/4 (75%) ovarian cancer cell lines (OVCA43, OVCA432, SKOV3) were positive. The median follow up of the patient population was 25 months (range 0.5–119). Tumor expression of BORIS did not correlate with stage, grade or histology. The median survival for BORIS positive patients was 49 months (CI:35,64) compared with 40 months (CI:26,54) for BORIS negative patients (not significant). Conclusion: BORIS is a novel CTA with high frequency expression in EOC. Although the expression of this antigen does not appear to influence survival, the tissue restricted expression pattern, role in epigenetic re-programming, and potential immunogenicity makes BORIS an attractive target for antigen-specific immunotherapy in EOC. The characterization of additional CTA with a frequent expression in EOC is warranted to allow for the development of polyvalent vaccines. No significant financial relationships to disclose.