Expression and serum levels of the neural cell adhesion molecule L1-like protein (CHL1) in gastrointestinal stroma tumors (GIST) and its prognostic power

// Karl-Frederick Karstens 1 , Eugen Bellon 1 , Adam Polonski 1 , Gerrit Wolters-Eisfeld 1 , Nathaniel Melling 1 , Matthias Reeh 1 , Jakob R. Izbicki 1 and Michael Tachezy 1 1 Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg Eppendor, Hamburg, Germany Correspondence to: Karl-Frederick Karstens, email: k.karstens@uke.de Keywords: neural cell adhesion molecule L1-like protein (CHL1); gastrointestinal stroma tumor (GIST); survival; prognosis; serum Received: December 31, 2019     Accepted: March 03, 2020     Published: March 31, 2020 ABSTRACT Introduction: Diagnosis of gastrointestinal stroma tumors (GIST) is based on the histological evaluation of tissue specimens. Reliable systemic biomarkers are lacking. We investigated the local expression of the neural cell adhesion molecule L1-like protein (CHL1) in GIST and determined whether soluble CHL1 proteoforms could serve as systemic biomarkers. Material and Methods: Expression of CHL1 was analyzed in primary tumor specimens and metastases. 58 GIST specimens were immunohistochemically stained for CHL1 on a tissue microarray (TMA). Systemic CHL1 levels were measured in sera derived from 102 GIST patients and 91 healthy controls by ELISA. Results were statistically correlated with clinicopathological parameters. Results: CHL1 expression was detected in GIST specimens. Reduced tissue expression was significantly associated with advanced UICC stages ( p = 0.036) and unfavorable tumor localization ( p = 0.001). CHL1 serum levels are significantly elevated in GIST patients ( p < 0.010). Elevated CHL1 levels were significantly associated with larger tumors ( p = 0.023), advanced UICC stage ( p = 0.021), and an increased Fletcher score ( p = 0.041). Moreover, patients with a higher CHL1 serum levels displayed a significantly shortened recurrence free survival independent of other clinicopathological variables. Conclusion: Local CHL1 expression and serum CHL1 levels show a reverse prognostic behavior, highlighting the relevance of proteolytic shedding of the molecule. The results of the study indicate a potential role of serum CHL1 as a diagnostic and prognostic marker in GIST.