PD-L1 expression and microsatellite instability in tumors of unknown primary site.

Abstract

2635 Background: Cancer of unknown primary site is a heterogeneous group of tumors for which the origin remains unknown, despite detailed investigation. Its clinical presentation occurs due to symptoms resulting from metastasis, which can be influenced not only by biological processes of the tumor, but also due to regulatory processes in the tumor microenvironment such as PD-L1. Microsatellite instability (MSI) is a predictive biomarker for cancer immunotherapy and its status as well as co-occurrence with PD-L1 expression is poorly evaluated. The aim of this study was to evaluate the expression of PD-L1 and the status of MSI in tumors of unknown primary site and their possible associations with clinical-pathological characteristics and clinical outcomes in patients with this type of tumor. Methods: The PD-L1 expression was evaluated using the immunohistochemistry technique and measured by CPS and TPS scores. MSI status was assessed using a hexa-plex marker panel by polymerase chain reaction followed by fragment analysis. Overall survival was analyzed using the Kaplan Meier method and comparisons of the curves using the log rank test. Results: Of the 121 conclusive cases for MSI status, only two cases (1,6%) were MSI-High. PD-L1 expression, assessed by both TPS and CPS, was positive in approximately 18% of 108 conclusive cases. PD-L1 expression is significantly less frequent in patients with a predominance of hepatic or bone metastasis and more frequent in patients with a predominance of nodal metastasis. The median overall survival was about 4 months, and the predominance of liver metastases was associated with a worse prognosis, while the use of chemotherapy and low ECOG-PS were associated with better survival. PD-L1 expression was associated with better overall survival. Conclusions: PD-L1 is expressed in a subset of patients with cancer of unknown primary site, while MSI is a rare event. It is necessary to better explore the microenvironment of this type of tumor as well as the role of immunotherapy to change such a dismal clinical outcome.