Harvard Cancer Center,
Keywords: cancer, Diagnostics, Bioimaging
Summary:Sialyl-Thomsen-nouveau antigen (STn), a tumor-associated carbohydrate antigen (TACA) is elevated in several solid tumors, including ovarian cancer (OvCa). OvCa is the most lethal of the gynecologic cancers in the US and increased STn levels correlate with chemo-resistance and decreased survival. Therefore, we postulate that a highly specific antibody directed against the carbohydrate and not the protein would provide therapeutic and/or diagnostics opportunities. More recently, we tested a highly specific anti-STn antibody with high binding affinity that was developed through a proprietary platform. Subsequent study of this anti-STn-antibody as an antibody-drug conjugate (ADC) demonstrated its effectiveness in in vitro and in vivo models of OvCa. Our pre-clinical findings and those by others hinted that STn might also serve as a relevant OvCa biomarker for discriminating malignant from benign cases. For this investigation, we designed and optimized a custom ELISA to detect STn levels in human serum. After optimization, our objective was to determine in a pilot study whether we could distinguish between benign and malignant serum samples. The assay was employed on banked serum samples derived from patients diagnosed with benign gynecologic disease such as endometriosis, fibroids and others and serum from patients diagnosed with high grade OvCa. Serum samples were all collected from consented patients under an approved IRB protocol. Based on our analysis, we determined the areas under the receiver operating characteristic curves to compare how STn values associated with malignant or benign conditions. Our STn assay demonstrated the ability to distinguish between benign and malignant cases with accuracy. Interestingly, in patients with malignancy and a CA-125 < 35 mIU/ml, roughly, 75% were found to have elevated STn above the cutoff value. Thus, we postulate that the sensitivity of CA-125 would be significantly improved if elevated levels of STn were integrated as a biomarker. To determine whether circulating STn levels mirrored that which is detected in the tumor, we identified a subset of samples with high STn and a subset of samples with low STn levels and assessed STn in their matching formalin fixed, paraffin embedded tumor by immunohistochemistry (IHC) using this highly specific STn antibody. Albeit this is a small sample subset there was an association between serum STn and tumor STn levels. Collectively, these data suggest that serum STn levels may improve the sensitivity of CA-125 to detect malignancy in an unknown adnexal mass, making it a valuable biomarker for clinical triage.