{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:01:44Z","timestamp":1792119704802,"version":"4.4.0"},"reference-count":30,"publisher":"American Medical Association (AMA)","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Surg"],"published-print":{"date-parts":[[2025,12,1]]},"abstract":"\n Importance<\/jats:title>\n Contemporary guidelines recommend sentinel lymph node biopsy (SLNB) for patients with melanoma with predicted risk of SLN metastasis greater than 10% and consideration of SLNB when the risk is 5% to 10%. A gene expression profile (GEP)\u2013based test that can accurately identify patients with a low risk of SLN metastasis would refine selection for SLNB.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To establish the predictive capability of the combined clinicopathological factors and GEP (CP-GEP) test to identify patients with primary cutaneous melanoma who can safely forgo SLNB and to investigate the prognostic value of CP-GEP regarding the outcome in patients with cutaneous melanoma after a negative SLNB (not reported herein).<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This prognostic study was conducted from September 2021 to June 2024 at 9 academic medical centers with experienced melanoma surgeons. Included were patients with biopsy-proven invasive cutaneous melanoma with T1 to T3 tumors and clinically negative regional LNs. All patients were deemed candidates for SLNB using standard clinical criteria. GEP was performed on formalin-fixed, paraffin-embedded tissue from the primary melanoma biopsy. Analyses were performed from December 2024 to August 2025.<\/jats:p>\n <\/jats:sec>\n \n Intervention<\/jats:title>\n CP-GEP testing to determine risk of having a positive SLNB in patients with T1 to T3 cutaneous melanoma who were considered appropriate candidates for the procedure based on standard clinical parameters.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n CP-GEP results were reported as low risk or high risk; the primary outcome measure was negative predictive value (NPV) in low-risk cases. Analyses included NPV assessment by tumor (T) subcategory, primary site, and age.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n A total of 1761 patients (median [IQR] age, 64 [53-72] years; 997 male [56.6%]) underwent SLNB (310 [17.6%] SLN positive) and had a successful CP-GEP test; GEP was successful in 97.7% of samples. A total of 651 patients (37.0%) were considered low risk by CP-GEP. Among low-risk cases, 46 (7.1%) were SLN positive, and NPV was 92.9% (95% CI, 90.7%-94.8%). High-risk cases had a 23.8% (264 of 1110) SLN-positive rate. The percentage of cases with low-risk CP-GEP declined with increasing T category (T1 = 346 of 507 [68.2%]; T2 = 295 of 897 [32.9%]; T3 = 10 of 357 [2.8%]). CP-GEP results were consistent in discriminating SLN-positive rates across primary sites, histologic subtypes, and mitotic count categories. In 2 large subsets, clinical stage IB (n\u2009=\u20091187) and patients 65 years and older (n\u2009=\u2009832), 6.5% (95% CI, 4.6%-8.8%) of low-risk clinical stage IB cases and 6.6% (95% CI, 4.2%-9.7%) of all low-risk cases in patients 65 years and older were SLN positive vs 18.3% (95% CI, 15.3%-21.6%) and 20.3% (95% CI, 16.8%-24.2%) for high-risk cases, respectively.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this multicenter, prospective, blinded, prognostic study, the CP-GEP test reliably identified patients with melanoma with less than 10% SLN metastasis risk. SLN metastasis rates were\u2009approximately\u20093-fold greater for high-risk vs low-risk CP-GEP cases. In appropriately selected patients, the CP-GEP test may add value for shared patient-surgeon decision-making.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamasurg.2025.4399","type":"journal-article","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T15:31:18Z","timestamp":1761147078000},"page":"1358","source":"Crossref","is-referenced-by-count":18,"title":["Gene Expression Profile\u2013Based Test to Predict Melanoma Sentinel Node Status"],"prefix":"10.1001","volume":"160","author":[{"given":"Tina J.","family":"Hieken","sequence":"first","affiliation":[{"name":"Departments of Surgery and Laboratory Medicine & Pathology, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E.","family":"Egger","sequence":"additional","affiliation":[{"name":"Hiram C. Polk Jr, MD Department of Surgery, The University of Louisville School of Medicine, Louisville, Kentucky"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina V.","family":"Angeles","sequence":"additional","affiliation":[{"name":"Departments of Surgery, Pathology and Dermatology, The University of Michigan Rogel Cancer Center, Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Hyngstrom","sequence":"additional","affiliation":[{"name":"Departments of Surgery and Dermatology, The Huntsman Cancer Institute, University of Utah, Salt Lake City"},{"name":"Department of Surgery, Rush University, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin E.","family":"Burke","sequence":"additional","affiliation":[{"name":"Department of Surgery and Pathology, The University of Kentucky, Lexington"},{"name":"Department of Surgery, The Ohio State University, Columbus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Lowe","sequence":"additional","affiliation":[{"name":"Department of Surgery, Emory University, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia M.","family":"Beasley","sequence":"additional","affiliation":[{"name":"Department of Surgery, Duke University, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edmund K.","family":"Bartlett","sequence":"additional","affiliation":[{"name":"Departments of Surgery and Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott C.","family":"Bresler","sequence":"additional","affiliation":[{"name":"Departments of Surgery, Pathology and Dermatology, The University of Michigan Rogel Cancer Center, Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly L.","family":"Harms","sequence":"additional","affiliation":[{"name":"Departments of Surgery, Pathology and Dermatology, The University of Michigan Rogel Cancer Center, Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan S.","family":"Zager","sequence":"additional","affiliation":[{"name":"Departments of Cutaneous Oncology and Pathology, Moffitt Cancer Center & Research Institute, Tampa, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia S.","family":"Lehman","sequence":"additional","affiliation":[{"name":"Departments of Surgery and Laboratory Medicine & Pathology, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nabil","family":"Wasif","sequence":"additional","affiliation":[{"name":"Department of Surgery, Mayo Clinic Arizona, Scottsdale"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay P.","family":"Bagaria","sequence":"additional","affiliation":[{"name":"Department of Surgery, Mayo Clinic Jacksonville, Jacksonville, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly M.","family":"McMasters","sequence":"additional","affiliation":[{"name":"Hiram C. Polk Jr, MD Department of Surgery, The University of Louisville School of Medicine, Louisville, Kentucky"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Wada","sequence":"additional","affiliation":[{"name":"Departments of Surgery and Dermatology, The Huntsman Cancer Institute, University of Utah, Salt Lake City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prakash","family":"Pandalai","sequence":"additional","affiliation":[{"name":"Department of Surgery and Pathology, The University of Kentucky, Lexington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith A.","family":"Delman","sequence":"additional","affiliation":[{"name":"Department of Surgery, Emory University, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Surgery, Duke University, Durham, North 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