131P - Trop 2 and its overexpression in metastatic colorectal cancer patients (mCRCp): Biological, clinical and therapeutic implications

Background

Trop 2 is a transmembrane intracellular signal transducer glycoprotein related to tumor proliferation. Targeting therapy against Trop2 is limited only to triple-negative breast cancer, but its role in mCRC remains poorly defined. The aim of this study is to elucidate Trop2’s biological role in mCRC, its prognostic and therapeutic implication.

Methods

We investigated prospectively 56 consecutive mCRCp from January 2016 to May 2023 and we analyzed respectively tissues from primary tumor (n.56) and synchronous and metachronous metastastic lesions (n.336). The specimens immunohistochemically stained for Trop2, Kras, B-raf, MSI and HER-2 were reviewed. We evaluated the Trop2 H-score distribution in the three cohorts: (1) primary tumor, (2) visceral metastases, (3) bone metastases and the different sites were divided in two groups based on Trop2 expression (high vs low). Clinic-pathological features were also matched with genomic and expression profiles.

Results

Moderate to strong membranous expression of Trop2 in at least 10% of tumor cells was present in 13/56 cases (23.2%) of cohort 1, 80/256 cases (31.2%) of cohort 2, and 71/80 cases (87.6%) of cohort 3. There was no difference in Trop2 H-score distribution between cohort 1 and 2 (Mann Whitney U test p=.966) but it is statistically different when combining cumulative data of cohort 1 and 2 vs cohort 3 (Mann Whitney U p<0.01). High Trop2 Score was significantly correlated with increased K-ras and B-raf mutational status, 83% vs 17% (Mann Whitney U p<0.01), and it was an independent poor prognostic factor for overall survival in cohort 3. No correlations were seen with MSI and HER-2 status.

Conclusions

Trop2 expression is a strong prognostic biomarker for bone mCRC. In bone metastatic disease Trop2 expression could induce a different biological aggressiveness, causing resistance to common therapeutic drugs and radiotherapy. Targeting Trop2 might be a useful treatment approach for these patients but further evaluations and clinical trials on efficacy and predictive value of Trop2 expression are needed.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

The authors.

Funding

BMAT ILAB s.r.l.s.

Disclosure

All authors have declared no conflicts of interest.