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Combined Staining of TAG-72, MUC1, and CA125 Improves Labeling Sensitivity in Ovarian Cancer: Antigens for Multi-targeted Antibody-guided Therapy

Subhash C. Chauhan, Namita Vinayek, Diane M. Maher, Maria C. Bell, Katrina A. Dunham, Michael D. Koch, Yuhlong Lio and Meena Jaggi

Cancer Biology Research Institute, Sanford Research/USD (SCC,NV,DMM,KAD,MJ), Department of Obstetrics and Gynecology (SCC,MCB,MJ), Department of Laboratory Medicine (MDK), Sanford School of Medicine, The University of South Dakota, Sioux Falls, South Dakota, and Department of Mathematics, The University of South Dakota, Vermillion, South Dakota (YL)

Correspondence to: Subhash C. Chauhan, PhD, Cancer Biology Research Institute, Sanford Research/USD, Department of Obstetrics and Gynecology and Basic Biomedical Science Division, Sanford School of Medicine, The University of South Dakota, 1400 W. 22^nd St., Sioux Falls, SD 57105. E-mail: subhash.chauhan{at}usd.edu

Single antigen-targeted intraperitoneal radioimmunotherapy for ovarian cancer has shown limited success. Due to the heterogeneous expression of tumor antigens on cancer cells, a multi-antigen targeting approach appears logical to augment the therapeutic efficacy of antibody-guided therapy. In the interest of developing this novel approach, ovarian cancer tissue microarray slides containing cancer and benign/non-neoplastic tissue samples (n=92) were processed for single-, double-, and triple-antigen labeling using antibodies for the tumor-associated antigens TAG-72, MUC1, and CA125. Among all ovarian cancer types, 72%, 61%, and 50% of the samples showed immunolabeling for TAG-72, MUC1, and CA125, respectively. Expression level of these antigens was significantly (p<0.005) higher in advanced stage carcinomas compared with early stage. Of the 48 epithelial ovarian cancer samples, individual anti-TAG-72, MUC1, and CA125 antibody probing showed labeling in 89.5%, 87.5%, and 73.0% of the cases, respectively. In the majority of the cancer samples (>70%), a heterogeneous labeling pattern was observed (only 30–40% of the cancer cells within the sample were labeled). However, upon combining the three antigens (triple-antigen labeling), 98% of the epithelial ovarian cancer samples were labeled and >95% of the cancer cells within each sample were labeled. Our data indicate that the heterogeneous expression of cancer antigens appears to be a major obstacle in antibody-guided therapy, and this can be overcome by multiple antigen targeting. Therapeutic efficacy of antibody-guided therapy for ovarian cancer treatment will be enhanced by the combined targeting of TAG-72, MUC1, and CA125. (J Histochem Cytochem 55:867–875, 2007)

Key Words: ovarian cancer • ovarian cancer therapy • TAG-72 • MUC1 • CA125

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