(P 70) EPIDEMIOLOGY AND POTENTIAL CLINICAL RELEVANCE OF CONTACTIN-4 EXPRESSION IN SOFT TISSUE SARCOMA

Objective: Contactin-4 (CNTN4) is a cell adhesion protein that functions as an immune checkpoint, by suppressing T-cell activation through its interaction with the amyloid precursor protein. High levels of CNTN4 expression has been observed in a number of human cancers (e.g. gallbladder, pancreatic, endometrial, and prostate tumors) and was also recently studied as a promising target for treatment with antibody-drug conjugates (ADC). We aimed to evaluate the epidemiology of CNTN4 expression in soft tissue sarcoma (STS) and to assess its potential as a prognostic biomarker.

Methods: The expression of CNTN4 was evaluated by immunohistochemistry (IHC) on tissue microarrays (TMA), constructed from tumor specimens collected from patients with leiomyosarcoma (LMS; n=128 samples), myxofibrosarcoma (MFS; n=121), angiosarcoma (AS; n=79), liposarcoma (LPS; n=60) and gastrointestinal stromal tumor (GIST; n=63). IHC results were quantified using the H-score (staining intensity * percentage of positive cells). The H-score distribution was used to define the threshold of 55, which was utilized to distinguish between low (H-score ≤55) and high (>55) CNTN4 expression. These categories were then used to correlate with patient’s progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier curve and log-rank test. GraphPad software was utilized for the statistical analysis, with p-value < 0.05 being considered as statistically significant.

Results: Overall the majority of STS samples analyzed exhibited positivity for CNTN4, with 55.0% and 28.6% of the samples demonstrating high and low immunopositivity, respectively. A high level of expression was detected in 63.3% of LMS, 58.7% of MFS, 58.2% of AS and 54.0% of GIST, while in LPS high expression was observed in only 26.7%. High CNTN4 expression was found to be significantly associated with worse prognosis (both PFS and OS) in the entire cohort of STS. In the subtype-specific analysis, high CNTN4 expression was significantly associated with shorter PFS in MFS and LPS patients, and with a worse OS in the latter only.

Conclusion: The high frequency and the high level of CNTN4 expression indicate its potential as both a prognostic biomarker and a novel therapeutic target. Our study also supports also the development of anti-CNTN4 therapies, including ADCs for the treatment of STS patients.