Abstract C001: Retrospective analysis of TROP2 expression in colorectal cancer (CRC) primary tumors and liver metastases (LM) and its correlation with clinical factors
Authors: Lentz Robert W , Barnett Miriam , Gerber Michele , Kaplan Jeffrey , van Bokhoven Adrie , Torkko Kathleen C 
Published: December 2023

Background: Trophoblast cell surface antigen 2 (TROP2) is a transmembrane glycoprotein which is upregulated in CRC, is associated with tumorigenesis, and may serve as a drug target. We aimed to measure TROP2 expression by immunohistochemistry in CRC LM and primary tumors, and to determine how TROP2 expression correlates with prognosis and baseline clinical factors.

Methods: TROP2 immunohistochemistry was retrospectively performed by a pathologist (ab214488; Abcam, Cambridge, UK) in paraffin-embedded CRC LM and primary tumor specimens (biopsy or resection, stored at the University of Colorado Surgical Pathology Archive) from adult patients between January 2006 and June 2022. Baseline clinical and survival data was collected. Differences in TROP2 frequency (range: 0-4), intensity (range: 0-3), and frequency x intensity combined scores (range: 0-12) for paired CRC primary and LM specimens were analyzed using a paired t-test. Additional statistical analyses included nonparametric Spearman’s correlation test (correlation of scores between LM and primary tumor), Mann Whitney U test (effect of prior systemic cancer treatment on TROP2 expression), Kaplan-Meier method (survival rates based on TROP2 expression), and log-rank test (differences in survival).

Results: TROP2 was expressed in 100% (60/60) of CRC primary and 93% (52/56) of LM specimens, including 50 CRC primary-LM pairs and additional unpaired specimens (10 primary and 6 LM). Among all specimens, primary and LM specimens both had a median intensity score of 2, whereas CRC specimens had a slightly higher frequency score than LM specimens (2 vs. 1, respectively). In paired samples, the TROP2 frequency, intensity, and combined score distribution varied slightly between primary and LM specimens. The median intensity was higher in primary vs LM specimens (3 vs 2, respectively), mean difference was 0.26 (p=0.08), and correlation was weak (Spearman r=0.29, p=0.04). Similarly, the median frequency was higher in primary vs LM specimens (2 vs 1, respectively), mean difference was 0.20 (p=0.21), with moderate correlation (Spearman r=0.55, p&lt;0.0001). The median combined score was higher in primary vs LM specimens (4 vs 3, respectively), mean difference was 0.98 (p=0.04), with moderate correlation (Spearman r=0.51, p=0.0001). Prior systemic cancer therapy did not significantly affect TROP2 intensity, frequency, or combined score in primary or LM specimens (data to be presented). Overall survival was not significantly different between low (&lt;5) or high (≥5) TROP2 combined score (stratified by the median value) for primary (log-rank p=0.67) or LM specimens (log-rank p=0.66). Similarly, there was no difference in overall survival stratified by TROP2 frequency or intensity in CRC primary or LM (data to be presented).

Conclusions: TROP2 expression was observed in both primary CRC and LM specimens, and the frequency x intensity combined score was significantly higher in primary CRC specimens compared to paired LM. Higher TROP2 expression in either primary tumors or LM did not correlate with overall survival.

Citation Format: Robert W Lentz, Miriam Barnett, Michele Gerber, Jeffrey Kaplan, Adrie van Bokhoven, Kathleen C Torkko. Retrospective analysis of TROP2 expression in colorectal cancer (CRC) primary tumors and liver metastases (LM) and its correlation with clinical factors [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr C001.