Differential diagnosis of prostatic adenocarcinomas is based on histopathologic analysis of tumor tissue obtained by transrectal ultrasound (TRUS)-guided biopsies. However, such invasive biopsies are associated with pain, procedural expenses, sequelae, and risk of complications. Though immunocytochemistry (ICC) profiling of circulating tumor cells (CTCs, defined as EpCAM+, panCK+, CD45-) has been previously attempted for diagnosis in some cancers, it has been unviable due to limited yields of CTCs. For the first time we used enrichment of CTCs that permit meaningful ICC profiling for diagnosis of prostate cancers in suspected cases as contradistinguished from cases of benign enlargement of prostate (BEP). We obtained 15 mL of venous blood draw from 650 individuals, of whom 65 had a confirmed diagnosis of either prostate adenocarcinoma and 585 were diagnosed with benign prostate hyperplasia. CTCs were enriched from PBMCs fraction using an epigenetically acting enrichment process that is lethal towards normal (nonmalignant) cells but confers survival privilege on apoptosis-resistant CTCs. Harvested CTCs were confirmed by immunostaining for EpCAM and pan-CK. ICC profiling of these CTCs was also performed with organ-specific markers PSMA and AMACR. Viable CTCs could be obtained from 58 samples (89.2%) out of 65 confirmed prostate cancer cases. Among the 40 samples that were characterized by deep ICC profiling, all samples (100%) were positive for PSMA and AMACR. Among the benign cases, CTCs were observed in 10 samples (1.7%), of which all 10 were positive for PSMA but negative for AMACR. These patients are being followed up. Possibility of other cancers is not ruled out in these patients. Our results show that ICC-based characterization of CTCs can provide necessary diagnostic information noninvasively to substitute for conventional procedures dependent on tissue extraction.

Citation Format: Darshana A. Patil, Dadasaheb Akolkar, Revati Patil, Pooja Fulmali, Pradip Fulmali, Akshay Ainwale, Navin Srivastava, Vineet Datta, Cynthe Sims, Ajay Srinivasan, Rajan Datar. Encyclopedic noninvasive liquid biopsies for differential diagnosis in prostate cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr B61.