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We evaluated concordance between circulating tumor cell (CTC) AR and SYP expression patterns and evidence of NE differentiation defined by clinical, pathologic, and genomic features.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>CTCs from patients with metastatic castration\u2010resistant prostate cancer (mCRPC) were analyzed using the RareCyte platform with quantitative immunofluorescence imaging for SYP and AR. In patients with \u2265\u20095 CTCs, associations of CTC phenotype with PSA at collection and overall survival (OS) were assessed using the Wilcoxon rank\u2010sum test, Fisher's exact test, and Kaplan\u2013Meier analysis. Patients were retrospectively classified as AR\u2010positive adenocarcinoma or NE\u2010differentiated based on clinical, pathologic, and genomic data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The AR\/SYP CTC assay was analytically validated using cell\u2010line spike\u2010in models, achieving &gt;\u200990% accuracy for both biomarkers. Of 52 patients with mCRPC, 27 had \u2265\u20095 evaluable CTCs and were included in the primary CTC phenotype analyses. The NE\u2010differentiated cohort had a higher fraction of SYP\u2010positive CTCs (median 28.6% vs 0.0%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0084), whereas the AR\u2010positive adenocarcinoma cohort had a higher fraction of AR\u2010positive CTCs (median 96.7% vs 0.0%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0004). Classification based on high AR or SYP expression (\u2265\u200980% of CTCs positive) significantly distinguished cohorts and was associated with tissue histology (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0048). PSA at CTC collection was lower in the NE\u2010differentiated cohort (median 3.83 vs 486.89\u2009ng\/mL; 95% CI: \u22121016 to \u2212190.9). OS did not significantly differ between groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>SYP and AR CTC expression showed strong concordance with tissue histology and clinical features of NE differentiation and AR\u2010positive adenocarcinoma. These findings support the feasibility of CTC immunophenotyping to characterize lineage\u2010associated phenotypes including SYP\u2010expressing NE differentiation in mCRPC. Prospective validation in larger cohorts with matched tissue biopsies is needed to define the clinical utility of this approach.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pros.70267","type":"journal-article","created":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T17:44:45Z","timestamp":1791740685000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Circulating Tumor Cell Synaptophysin and Androgen Receptor Expression Reflect Prostate Cancer Phenotypes in Metastatic Disease"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-0001-8787","authenticated-orcid":false,"given":"Ethan","family":"Lo","sequence":"first","affiliation":[{"name":"Clinical Research Division Fred Hutchinson Cancer Center Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisa","family":"Clein","sequence":"additional","affiliation":[{"name":"Clinical Research Division Fred Hutchinson Cancer Center Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Tam","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Washington Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Trimble","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Washington Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Hardin","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Washington Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arturo","family":"Ramirez","sequence":"additional","affiliation":[{"name":"RareCyte, Inc., 2601 4th Ave #500 Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Kaldjian","sequence":"additional","affiliation":[{"name":"RareCyte, Inc., 2601 4th Ave #500 Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan Y.","family":"Yu","sequence":"additional","affiliation":[{"name":"Clinical Research Division Fred Hutchinson Cancer Center Seattle WA USA"},{"name":"Division of Hematology and Oncology, Dept. of Medicine University of Washington Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1365-0702","authenticated-orcid":false,"given":"Heather H.","family":"Cheng","sequence":"additional","affiliation":[{"name":"Clinical Research Division Fred Hutchinson Cancer Center Seattle WA USA"},{"name":"Division of Hematology and Oncology, Dept. of Medicine University of Washington Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd A.","family":"Yezefski","sequence":"additional","affiliation":[{"name":"Clinical Research Division Fred Hutchinson Cancer Center Seattle WA USA"},{"name":"Division of Hematology and Oncology, Dept. of Medicine University of Washington Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew C.","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Clinical Research Division Fred Hutchinson Cancer Center Seattle WA USA"},{"name":"Division of Hematology and Oncology, Dept. of Medicine University of Washington Seattle WA USA"},{"name":"Human Biology Division Fred Hutchinson Cancer Center Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3965-3394","authenticated-orcid":false,"given":"Petros","family":"Grivas","sequence":"additional","affiliation":[{"name":"Clinical Research Division Fred Hutchinson Cancer Center Seattle WA USA"},{"name":"Division of Hematology and Oncology, Dept. of Medicine University of Washington Seattle WA 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