PD-L1 expression and microsatellite instability (MSI) in cancer of unknown primary site

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BACKGROUND: Cancer of unknown primary site (CUP) is a heterogeneous group of tumors for which the origin remains unknown. Clinical outcomes might be influenced by regulatory processes in its microenvironment. 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. We aim to evaluate the expression of PD-L1 and the status of MSI in CUP and their possible associations with clinical-pathological features. METHODS: The combined positive score (CPS) PD-L1 expression was evaluated by immunohistochemistry. MSI status was assessed using a hexa-plex marker panel by polymerase chain reaction followed by fragment analysis. RESULTS: Among the 166 cases, MSI analysis was conclusive in 120, being two cases MSI-positive (1.6%). PD-L1 expression was positive in 18.3% of 109 feasible cases. PD-L1 expression was significantly associated with non-visceral metastasis and a dominance of nodal metastasis. The median overall survival (mOS) was 3.7 (95% CI 1.6 – 5.8) months and patients who expressed PD-L1 achieved a better mOS compared to those who did not express PD-L1 (18.7 versus 3.0 months, p-value: <.001). ECOG-PS equal or more than two and PD-L1 expression were independent prognostic factors in multivariate analysis (2.37 and 0.42 respectively). CONCLUSION: PD-L1 is expressed in a subset (1/5) of patients with CUP and associated with improved overall survival, while MSI is a rare event. There is an urge to explore better the tumor microenvironment as well as the role of immunotherapy to change such a worse clinical outcome.