{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T11:08:36Z","timestamp":1791544116144,"version":"4.3.4"},"reference-count":21,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T00:00:00Z","timestamp":1662681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>In recent years, the preferentially expressed antigen in melanoma (PRAME) has also been used in the histopathological diagnosis of melanocytic lesions, in order to understand if it could constitute a valid, inexpensive, and useful resource in dermatopathological fields. We performed a double-center study to evaluate whether the data on the usefulness and possible limitations of PRAME could also be confirmed by our group. From 1 December 2021 to 29 March 2022, we collected 275 cases of melanocytic lesions that were immunostained with PRAME (Ab219650) and rabbit monoclonal antibody (Abcam). To better correlate the PRAME expression with its nature (benign, uncertain potential for malignancy, or malignant), we categorized PRAME tumor cells\u2019 percentage positivity and intensity of immunostaining in a cumulative score obtained by adding the quartile of positive tumor cells (0, 1+, 2+, 3+, 4+) to the PRAME expression intensity in tumor cells (0, 1+, 2+, 3+). Of these 275 lesions, 136 were benign, 12 were of uncertain potential for malignancy (MELTUMP or SAMPUS or SPARK nevus), and 127 were malignant. The immunoexpression of PRAME was completely negative in 125\/136 benign lesions (91.9%), with only a few positive melanocytes (1+) and intensity 1+ in the remaining 11 cases (8.1%). Of the 127 cases of melanoma (superficial spreading, lentigo maligna, and pagetoid histotypes), PRAME was strongly positive in 104\/127 cases (81.8%) with intensity 4+ and 3+. In 17 cases (13.3%; melanoma spindle and nevoid cell histotypes), PRAME was positive in percentage 2+ and with intensity ranging from 2+ to 3+. In 7 cases (5.5%) of desmoplastic melanoma, PRAME was 1+ positive and\/or completely negative. Of the 12 cases of lesions with uncertain potential for malignancy, the immunoexpression of PRAME was much more heterogeneous and irregularly distributed throughout the lesion. These data are perfectly in agreement with the current literature, and they demonstrate that the reliability of PRAME is quite high, but its use cannot cause physicians to disregard the morphological information and the execution of other ancillary immunohistochemical stains such as Melan-A, HMB-45, MiTF, and SOX-10.<\/jats:p>","DOI":"10.3390\/diagnostics12092197","type":"journal-article","created":{"date-parts":[[2022,9,12]],"date-time":"2022-09-12T20:52:25Z","timestamp":1663015945000},"page":"2197","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["PRAME Immunoexpression in 275 Cutaneous Melanocytic Lesions: A Double Institutional Experience"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0325-4316","authenticated-orcid":false,"given":"Gerardo","family":"Cazzato","sequence":"first","affiliation":[{"name":"Section of Pathology, Department of Emergency and Organ Transplantation (DETO), University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1287-4285","authenticated-orcid":false,"given":"Eliano","family":"Cascardi","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Turin, 10124 Turin, Italy"},{"name":"Pathology Unit, FPO-IRCCS Candiolo Cancer Institute, Str. Provinciale 142 Km 3.95, 10060 Candiolo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4676-0761","authenticated-orcid":false,"given":"Anna","family":"Colagrande","sequence":"additional","affiliation":[{"name":"Section of Pathology, Department of Emergency and Organ Transplantation (DETO), University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Belsito","sequence":"additional","affiliation":[{"name":"Pathology Unit, Humanitas Research Hospital and Humanitas University, 20089 Rozzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Lospalluti","sequence":"additional","affiliation":[{"name":"Section of Dermatology and Venereology, Department of Biomedical Sciences and Human Oncology (DIMO), University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Foti","sequence":"additional","affiliation":[{"name":"Section of Dermatology and Venereology, Department of Biomedical Sciences and Human Oncology (DIMO), University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Arezzo","sequence":"additional","affiliation":[{"name":"Section of Gynecology and Obstetrics, Department of Biomedical Sciences and Human Oncology (DIMO), University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3522-4648","authenticated-orcid":false,"given":"Miriam","family":"Dellino","sequence":"additional","affiliation":[{"name":"Section of Gynecology and Obstetrics, Department of Biomedical Sciences and Human Oncology (DIMO), University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4861-0727","authenticated-orcid":false,"given":"Nadia","family":"Casatta","sequence":"additional","affiliation":[{"name":"Innovation Department, Diapath S.p.A., Via Savoldini n.71, 24057 Martinengo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3287-7299","authenticated-orcid":false,"given":"Carmelo","family":"Lupo","sequence":"additional","affiliation":[{"name":"Innovation Department, Diapath S.p.A., Via Savoldini n.71, 24057 Martinengo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8757-088X","authenticated-orcid":false,"given":"Luigi","family":"Buongiorno","sequence":"additional","affiliation":[{"name":"Section of Legal Medicine, Interdisciplinary Department of Medicine, Bari Policlinico Hospital, University of Bari Aldo Moro, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7397-0097","authenticated-orcid":false,"given":"Alessandra","family":"Stellacci","sequence":"additional","affiliation":[{"name":"Section of Legal Medicine, Interdisciplinary Department of Medicine, Bari Policlinico Hospital, University of Bari Aldo Moro, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1058-7269","authenticated-orcid":false,"given":"Maricla","family":"Marrone","sequence":"additional","affiliation":[{"name":"Section of Legal Medicine, Interdisciplinary Department of Medicine, Bari Policlinico Hospital, University of Bari Aldo Moro, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4792-3545","authenticated-orcid":false,"given":"Giuseppe","family":"Ingravallo","sequence":"additional","affiliation":[{"name":"Section of Pathology, Department of Emergency and Organ Transplantation (DETO), University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0472-5338","authenticated-orcid":false,"given":"Eugenio","family":"Maiorano","sequence":"additional","affiliation":[{"name":"Section of Pathology, Department of Emergency and Organ Transplantation (DETO), University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4335-4776","authenticated-orcid":false,"given":"Leonardo","family":"Resta","sequence":"additional","affiliation":[{"name":"Section of Pathology, Department of Emergency and Organ Transplantation (DETO), University of Bari \u201cAldo Moro\u201d, 70124 Bari, 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J. Dermatopathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1056\/NEJMra052166","article-title":"Melanoma","volume":"355","author":"Miller","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_3","first-page":"152","article-title":"Diagnostic, Prognostic and Predictive Immunohistochemistry in Malignant Melanoma of the Skin","volume":"31","author":"Luca","year":"2018","journal-title":"Klin. Onkol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1097\/00125480-199901000-00002","article-title":"Melan-A, a new melanocytic differentiation marker","volume":"6","author":"Busam","year":"1999","journal-title":"Adv. Anat. Pathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1111\/j.1600-0560.1989.tb00010.x","article-title":"HMB-45 recognizes stimulated melanocytes","volume":"16","author":"Smoller","year":"1989","journal-title":"J. Cutan. Pathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1111\/j.1600-0560.2007.00891.x","article-title":"Immunohistochemical characteristics of melanoma","volume":"35","author":"Ohsie","year":"2008","journal-title":"J. Cutan. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.arcmed.2020.09.008","article-title":"Pathology-based Biomarkers Useful for Clinical Decisions in Melanoma","volume":"51","author":"Hwu","year":"2020","journal-title":"Arch. Med. Res."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Abrahamian, C., and Grimm, C. (2021). Endolysosomal Cation Channels and MITF in Melanocytes and Melanoma. Biomolecules, 11.","DOI":"10.3390\/biom11071021"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Cazzato, G., Mangialardi, K., Falcicchio, G., Colagrande, A., Ingravallo, G., Arezzo, F., Giliberti, G., Trilli, I., Loizzi, V., and Lettini, T. (2022). Preferentially Expressed Antigen in Melanoma (PRAME) and Human Malignant Melanoma: A Retrospective Study. Genes, 13.","DOI":"10.3390\/genes13030545"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1038\/modpathol.2013.244","article-title":"Expression of cancer-testis antigens MAGEA1, MAGEA3, ACRBP, PRAME, SSX2, and CTAG2 in myxoid and round cell liposarcoma","volume":"27","author":"Hemminger","year":"2014","journal-title":"Mod. Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.humpath.2016.12.006","article-title":"Cancer-testis antigen expression in synovial sarcoma: NY-ESO-1, PRAME, MAGEA4, and MAGEA1","volume":"61","author":"Iura","year":"2017","journal-title":"Hum. Pathol."},{"key":"ref_12","first-page":"4090","article-title":"Heterogeneous expression of the tumor-associated antigens RAGE-1, PRAME, and glycoprotein 75 in human renal cell carcinoma: Candidates for T-cell-based immunotherapies?","volume":"58","author":"Neumann","year":"1998","journal-title":"Cancer Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2208","DOI":"10.1016\/j.jtho.2016.08.120","article-title":"Safety and Immunogenicity of the PRAME Cancer Immunotherapeutic in Patients with Resected Non-Small Cell Lung Cancer: A Phase I Dose Escalation Study","volume":"11","author":"Pujol","year":"2016","journal-title":"J. Thorac. Oncol."},{"key":"ref_14","unstructured":"Elder, D.E., Massi, D., Scolyer, R.A., and Willemze, R. (2018). WHO Classification of Tumours, IARC Publications. [4th ed.]."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/978-1-62703-727-3_14","article-title":"Immunohistochemical diagnostic and prognostic markers for melanoma","volume":"1102","author":"Nosrati","year":"2014","journal-title":"Methods Mol. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/S1074-7613(00)80426-4","article-title":"Characterization of an antigen that is recognized on a melanoma showing partial HLA loss by CTL expressing an NK inhibitory receptor","volume":"6","author":"Ikeda","year":"1997","journal-title":"Immunity"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Gutzmer, R., Rivoltini, L., Levchenko, E., Testori, A., Utikal, J., Ascierto, P.A., Demidov, L., Grob, J.J., Ridolfi, R., and Schadendorf, D. (2016). Safety and immunogenicity of the PRAME cancer immunotherapeutic in metastatic melanoma: Results of a phase I dose escalation study. ESMO Open, 1.","DOI":"10.1136\/esmoopen-2016-000068"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1097\/PAS.0000000000001134","article-title":"PRAME Expression in Melanocytic Tumors","volume":"42","author":"Lezcano","year":"2018","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Gassenmaier, M., Hahn, M., Metzler, G., Bauer, J., Yazdi, A.S., Keim, U., Garbe, C., Wagner, N.B., and Forchhammer, S. (2021). Diffuse PRAME Expression Is Highly Specific for Thin Melanomas in the Distinction from Severely Dysplastic Nevi but Does Not Distinguish Metastasizing from Non-Metastasizing Thin Melanomas. Cancers, 13.","DOI":"10.3390\/cancers13153864"},{"key":"ref_20","first-page":"621","article-title":"[Application of immunohistochemical staining of PRAME in differential diagnosis between melanoma and melanocytic nevus]","volume":"51","author":"Du","year":"2022","journal-title":"Zhonghua Bing Li Xue Za Zhi"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1111\/cup.13818","article-title":"PRAME expression in melanocytic proliferations with intermediate histopathologic or spitzoid features","volume":"47","author":"Raghavan","year":"2020","journal-title":"J. Cutan. Pathol."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/9\/2197\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:28:36Z","timestamp":1760142516000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/9\/2197"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,9]]},"references-count":21,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["diagnostics12092197"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics12092197","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,9]]}}}