Abstract 7487: Construction of a reliable CTC detection method and validity evaluation of CTC markers in colorectal cancer

Abstract Even in modern times when medical technology has advanced, cancer remains a life-threatening disease, and recurrence and metastasis are major issues in cancer treatment. The characteristics of cancer cells change with progression and treatment. Therefore, timely evaluation on their characteristics and decision on the treatment strategy are required. Circulating tumor cells (CTCs) are released into blood vessels in solid tumors and promote metastasis by circulating in the blood. CTCs are thus attractive targets for liquid biopsy and can provide useful information for selection of appropriate treatment. To obtain reliable results from CTC testing, it is important to prove that the detected cells are derived from cancerous tissue. In molecular tests targeting CTCs, it is still unclear whether the detected cells are derived from cancer tissue displaying genetic mutations. Aiming to establish reliable CTC testing, we have developed a simple method using molecular imaging flow cytometry to detect APC gene mutation together with Cytokeratin and Vimentin, which are epithelial-mesenchymal transition markers. Since, abnormalities in the APC gene are detected in 60-70% of colorectal cancer patients, detecting such mutations provides strong evidence that the detected cells are derived from cancerous tissue. Here, we show that upon evaluation of analytical performance of our method using cells isolated from cancerous tissue, our method showed high concordance rate against APC gene mutation. A clinical proof-of-concept using 5 mL of whole blood from colorectal cancer patients revealed that counts of cells with APC mutation in blood and cells with Cytokeratin and/or Vimentin expression in blood are highly correlated. Our results demonstrated a pathological stage-dependent increase in the count and frequency of Cytokeratin and/or Vimentin positive CTCs. We believe that our study not only establishes a practical approach for identifying CTCs in cancer patients but also provides potential implications in clinical practice, prognostic evaluation, and selection of treatment strategies. Citation Format: Yusuke Takahashi, Yuichi Ijiri, Shiki Fujino, Nakhaei Elnaz, Ayuko Kishimoto, Kentaro Shirai, Shigeki Iwanaga, Masatoshi Yanagida, Ali Asgar Bhagat, Norikatsu Miyoshi. Construction of a reliable CTC detection method and validity evaluation of CTC markers in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7487.