{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"Research Square"}],"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T06:40:24Z","timestamp":1747204824587,"version":"3.40.5"},"posted":{"date-parts":[[2023,11,28]]},"group-title":"In Review","reference-count":49,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T00:00:00Z","timestamp":1701129600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,9,19]]},"abstract":"<title>Abstract<\/title>\n        <p><bold>BACKGROUND<\/bold>: 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. \n<bold>METHODS<\/bold>: 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. \n<bold>RESULTS<\/bold>: 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 \u2013 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: &lt;.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). \n<bold>CONCLUSION<\/bold>: 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.<\/p>","DOI":"10.21203\/rs.3.rs-3369856\/v1","type":"posted-content","created":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T20:07:42Z","timestamp":1701202062000},"source":"Crossref","is-referenced-by-count":0,"title":["PD-L1 expression and microsatellite instability (MSI) in cancer of unknown primary site"],"prefix":"10.21203","author":[{"given":"Jo\u00e3o Neif Antonio","family":"Junior","sequence":"first","affiliation":[{"name":"Funda\u00e7\u00e3o Pio XII: Hospital de Cancer de Barretos"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6561-7322","authenticated-orcid":false,"given":"Daniel D'Almeida","family":"Preto","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Pio XII: Hospital de Cancer de Barretos"}]},{"given":"Maria Eduarda Zanatta Neder","family":"Lazarini","sequence":"additional","affiliation":[{"name":"Barretos School of Health Sciences Dr Paulo Prata: Faculdade de Ciencias da Saude de Barretos Dr Paulo Prata"}]},{"given":"Marcos Alves","family":"de Lima","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Pio XII: Hospital de Cancer de Barretos"}]},{"given":"Murilo","family":"Bonatelli","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Pio XII: Hospital de Cancer de Barretos"}]},{"given":"Gustavo Noriz","family":"Berardinelli","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Pio XII: Hospital de Cancer de Barretos"}]},{"given":"Vinicius Duval da","family":"Silva","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Pio XII: Hospital de Cancer de Barretos"}]},{"given":"Celine","family":"Pinheiro","sequence":"additional","affiliation":[{"name":"Barretos School of Health Sciences Dr Paulo Prata: Faculdade de Ciencias da Saude de Barretos Dr Paulo Prata"}]},{"given":"Rui Manuel","family":"Reis","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Pio XII: Hospital de Cancer de Barretos"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0002-3507","authenticated-orcid":false,"given":"Flavio Mavignier","family":"C\u00e1rcano","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Pio XII: Hospital de Cancer de Barretos"}]}],"member":"297","reference":[{"year":"2019","author":"Greco FA","key":"ref1","unstructured":"Greco FA (2019) JD. 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