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Colorectal

Colorectal Parallel Session

22: Circulating Hybrid Cells as a Blood Based Screening Tool for Colorectal Neoplasia

Friday, March 22, 2024

10:42am – 10:52am ET

Location: C101

Abstract Presenter(s)

Ranish K. Patel, MD

Resident Physician
Oregon Health & Science University (OHSU), Department of Surgery, Division of Surgical Oncology, Knight Cancer Institute, Portland, OR 97239 USA
Portland, Oregon, United States

Submitter(s)

Ranish K. Patel, MD

Resident Physician
Oregon Health & Science University (OHSU), Department of Surgery, Division of Surgical Oncology, Knight Cancer Institute, Portland, OR 97239 USA
Portland, Oregon, United States

Author(s)

Ranish K. Patel, MD

Resident Physician
Oregon Health & Science University (OHSU), Department of Surgery, Division of Surgical Oncology, Knight Cancer Institute, Portland, OR 97239 USA
Portland, Oregon, United States
MP

Michael S. Parappilly, BS

Medical Student
Department of Cell, Developmental, and Cancer Biology, Oregon Health & Science University, Portland, OR 97239 USA, United States
SR

Shahrose Rahman, MD

Resident
Department of Surgery, Division of Gastrointestinal and General Surgery, Oregon Health & Science University, Portland, OR 97239 USA, United States
EL

Ethan S. Lu, n/a

Student
Department of Cell, Developmental, and Cancer Biology, Oregon Health & Science University, Portland, OR 97239 USA, United States
AN

Ashvin M. Nair, n/a

Student
Department of Cell, Developmental, and Cancer Biology, Oregon Health & Science University, Portland, OR 97239 USA, United States
EL

Emile J. Latour, MS

Biostatistician
Biostatistics Shared Resource, Knight Cancer Institute, Portland, OR 97239 USA, United States
Skye C. Mayo, MD MPH (he/him/his)

Associate Professor
Department of Surgery, Division of Surgical Oncology, Oregon Health & Science University; Knight Cancer Institute; Portland, OR 97239 USA
Portland, Oregon, United States
GC

Gregory A. Coté, MD MS

Professor & Division Head
Department of Medicine, Division of Gastroenterology & Hepatology, Oregon Health & Science University; Knight Cancer Institute; Portland, OR 97239 USA, United States
VT

Vassiliki L. Tsikitis, MD

Professor & Division Head
Department of Surgery, Division of Gastrointestinal and General Surgery, Oregon Health & Science University; Knight Cancer Institute; Portland, OR 97239 USA, United States
MW

Melissa H. Wong, PhD

Professor
Department of Cell, Developmental, and Cancer Biology, Oregon Health & Science University; Knight Cancer Institute; Portland, OR 97239 USA, United States

Disclosure(s):

Ranish K. Patel, MD: No financial relationships to disclose

Introduction: Colorectal cancer (CRC) is one of the most commonly diagnosed malignancies. While colonoscopy remains the gold-standard screening modality, it is invasive, costly, and does not capture those outside of screening thresholds. These factors highlight a need for a reliable, widely applicable blood-based screening biomarker. Circulating neoplastic-immune hybrid cells (CHC) have been identified in multiple gastrointestinal malignancies, including CRC, and correlate with disease burden and survival; we propose that CHCs represent a novel cell population that could serve as a screening biomarker for colorectal neoplasia.

Methods: Pre-procedural peripheral blood samples were prospectively collected from patients undergoing colonoscopy or surgical colectomy. Peripheral blood mononuclear cells (PBMC) were isolated from blood samples using standard ficoll separation protocols, processed onto slides, and immunostained. CHCs are identified by co-expression of pan-cytokeratin and CD45, enumerated CHCs were normalized to 50,000 PBMCs, and subsequently correlated to lesion pathology. CHC levels were compared between patient cohorts (healthy controls, colon polyps [CP], and CRC).

Results: We collected blood samples from n=39 participants (n=13 each: healthy control, CP, and CRC). In the CP group, 9 patients (69%) had tubular adenomas, 3 (23%) had sessile serrated lesions, and one had a tubulovillous adenoma. The median number of lesions per patient was 1 (range 1-20) and the median size of the largest lesion per patient was 27.5mm (range 2-40 mm). In patients with CRC, 8 (62%) had stage I/II disease, and 5 (38%) had stage III disease. Three patients (23%) had microsatellite instability-high (MSI-H) disease. Patients with MSI-H CRCs had fewer CHCs relative to those with microsatellite stable (MSS) CRC (p=0.010). CHC levels increased across the healthy, CP, and MSS CRC groups respectively (p< 0.001), with statistical significance in all pairwise comparisons (p< 0.001) (Figure).

Conclusions: CHCs were identified in patients with CP and CRC at higher levels than found in healthy controls; patients with MSS CRC have higher CHC levels compared to those with CP, while there was no significant difference in CHC levels when comparing the healthy and CP groups with the MSI-H CRC cohort. Longitudinal analyses of CHCs in patients after polyp removal is ongoing and has promise in monitoring residual disease and/or progression. These data indicate that CHC levels can successfully identify patients with colorectal neoplasia, and show promise as a screening modality.

Learning Objectives:

Recognize that circulating hybrid cells can be identified in patients with pre-cancerous colorectal polyps, as well as colorectal cancer.
Understand that circulating hybrid cell levels increase when comparing healthy patients, those with colon polyps, and those with microsatellite stable colorectal cancer, respectively.
Recognize that those with microsatellite instability-high colorectal cancers may have unique circulating hybrid cell profiles compared to those with microsatellite stable colorectal cancer.