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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\u2013pathological features.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among the 166 cases, MSI analysis was conclusive in 120, with two cases being 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\u20135.8) 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,\n                      <jats:italic>p<\/jats:italic>\n                      -value:\u2009&lt;\u2009.001). ECOG-PS equal to or more than two and PD-L1 expression were independent prognostic factors in multivariate analysis (2.37 and 0.42, respectively).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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 a need to explore better the tumor microenvironment as well as the role of immunotherapy to change such a bad clinical outcome.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10147-024-02494-3","type":"journal-article","created":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T16:01:41Z","timestamp":1711382501000},"page":"726-734","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["PD-L1 expression and microsatellite instability (MSI) in cancer of unknown primary site"],"prefix":"10.1007","volume":"29","author":[{"given":"Jo\u00e3o Neif Antonio","family":"Junior","sequence":"first","affiliation":[]},{"given":"Daniel D.\u2019Almeida","family":"Preto","sequence":"additional","affiliation":[]},{"given":"Maria Eduarda Zanatta Neder","family":"Lazarini","sequence":"additional","affiliation":[]},{"given":"Marcos Alves","family":"de Lima","sequence":"additional","affiliation":[]},{"given":"Murilo","family":"Bonatelli","sequence":"additional","affiliation":[]},{"given":"Gustavo Noriz","family":"Berardinelli","sequence":"additional","affiliation":[]},{"given":"Vinicius Duval","family":"da Silva","sequence":"additional","affiliation":[]},{"given":"C\u00e9line","family":"Pinheiro","sequence":"additional","affiliation":[]},{"given":"Rui Manuel","family":"Reis","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0002-3507","authenticated-orcid":false,"given":"Flavio Mavignier","family":"C\u00e1rcano","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2024,3,25]]},"reference":[{"key":"2494_CR1","first-page":"1720","volume-title":"Cancer of unknown primary site. 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