{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T16:29:56Z","timestamp":1787070596718,"version":"build-2736575974"},"reference-count":24,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Cyclic adenosine monophosphate (cAMP) is an intracellular signal transmitter involved in the regulation of melanocyte growth, proliferation, and melanogenesis. R21 is a monoclonal antibody against the soluble adenylyl cyclase (sAC) protein. Various nuclear and cytoplasmic R21 expression patterns in melanocytic lesions have been previously reported. Pan-nuclear staining was defined as specific for melanoma and was found supportive in the assessment of surgical margins.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>The aim of this study is to evaluate the different expression patterns of R21 immunostain and investigate its effectiveness in the differential diagnosis of cutaneous malignant and benign melanocytic lesions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Settings and Design:<\/jats:title>\n                    <jats:p>Fifty invasive cutaneous melanoma and 50 benign melanocytic proliferation were included in the study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods:<\/jats:title>\n                    <jats:p>Paraffin blocks that best reflected tumor morphology were studied via immunohistochemical staining for R21. For all patterns, the cases showing staining in 25% or more tumor cells were considered as positive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Statistical Analysis used:<\/jats:title>\n                    <jats:p>Yates\u2019 Chi-square, Pearson Chi-square exact test, Spearman correlation were used.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and Conclusions:<\/jats:title>\n                    <jats:p>Dot-like Golgi staining was characteristic for nevi (12\/50) and seen only in one melanoma. Pan-nuclear staining was striking for melanoma (36\/50). This pattern was observed in 2 dysplastic and 3 common melanocytic nevi too. None of the Spitz nevi expressed R21 in pan-nuclear pattern. For the diagnosis of melanoma, sensitivity and specificity of the pan-nuclear expression were 72% and 90%, respectively. Positive and negative predictive values were found as 87% and 76%. R21, a second-generation immunohistochemical marker, can be used in the differential diagnosis of benign and malignant melanocytic lesions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/ijpm.ijpm_1146_21","type":"journal-article","created":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T02:40:09Z","timestamp":1717036809000},"page":"804-809","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":1,"title":["The role of R21 expression in differential diagnosis of melanocytic lesions"],"prefix":"10.4103","volume":"66","author":[{"given":"Didem","family":"Turcan","sequence":"first","affiliation":[{"name":"Department of Pathology, Gaziantep Nizip State Hospital, Gaziantep, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6zg\u00fcl","family":"Pa\u015fao\u011flu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deniz","family":"Arik","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2023,2,3]]},"reference":[{"key":"R1-20240829","doi-asserted-by":"crossref","first-page":"2636","DOI":"10.1016\/j.bbadis.2014.08.016","article-title":"Investigation of cAMP microdomains as a path to novel cancer diagnostics","volume":"1842","author":"Desman","year":"2014","journal-title":"Biochim Biophys Acta"},{"key":"R2-20240829","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/modpathol.3801016","article-title":"IMP-3 is a novel progression marker in malignant melanoma","volume":"21","author":"Pryor","year":"2008","journal-title":"Mod Pathol"},{"key":"R3-20240829","doi-asserted-by":"crossref","first-page":"234","DOI":"10.4103\/idoj.IDOJ_8_18","article-title":"Immunohistochemistry in dermatopathology and its relevance in clinical practice","volume":"9","author":"Chatterjee","year":"2018","journal-title":"Indian Dermatol Online J"},{"key":"R4-20240829","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1159\/000246329","article-title":"Expression of cyclin D1 and p53 protein in various malignant skin tumors","volume":"192","author":"Inohara","year":"1996","journal-title":"Dermatology"},{"key":"R5-20240829","first-page":"13","article-title":"Diagnostic and prognostic biomarkers in melanoma","volume":"7","author":"Weinstein","year":"2014","journal-title":"J Clin Aesthet Dermatol"},{"key":"R6-20240829","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.abb.2014.07.003","article-title":"Cyclic AMP (cAMP) signaling in melanocytes and melanoma","volume":"563","author":"Rodriguez","year":"2014","journal-title":"Arch Biochem Biophys"},{"key":"R7-20240829","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1038\/jid.2009.440","article-title":"Soluble adenylyl cyclase defines a nuclear cAMP microdomain in keratinocyte hyperproliferative skin diseases","volume":"130","author":"Zippin","year":"2010","journal-title":"J Invest Dermatol"},{"key":"R8-20240829","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1001\/archdermatol.2011.338","article-title":"Soluble adenylyl cyclase antibody profile as a diagnostic adjunct in the assessment of pigmented lesions","volume":"148","author":"Magro","year":"2012","journal-title":"Arch Dermatol"},{"key":"R9-20240829","doi-asserted-by":"crossref","first-page":"3126","DOI":"10.1074\/jbc.M112.403279","article-title":"Type 10 soluble adenylyl cyclase is overexpressed in prostate carcinoma and controls proliferation of prostate cancer cells","volume":"288","author":"Flacke","year":"2013","journal-title":"J Biol Chem"},{"key":"R10-20240829","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/pcmr.12920","article-title":"Cyclic adenosine monophosphate (cAMP) signaling in melanocyte pigmentation and melanomagenesis","volume":"34","author":"Bang","year":"2021","journal-title":"Pigment Cell Melanoma Res"},{"key":"R11-20240829","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1073\/pnas.96.1.79","article-title":"Cytosolic adenylyl cyclase defines a unique signaling molecule in mammals","volume":"96","author":"Buck","year":"1999","journal-title":"Proc Natl Acad Sci"},{"key":"R12-20240829","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1081\/RRS-120014589","article-title":"Characterization of the human adenylyl cyclase gene family: cDNA, gene structure, and tissue distribution of the nine isoforms","volume":"22","author":"Ludwig","year":"2002","journal-title":"J Recept Signal Transduct"},{"key":"R13-20240829","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1073\/pnas.72.3.1097","article-title":"Development of a Mn2+-sensitive, \u201csoluble\u201d adenylate cyclase in rat testis","volume":"72","author":"Braun","year":"1975","journal-title":"Proc Natl Acad Sci"},{"key":"R14-20240829","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1002\/(SICI)1098-2795(200005)56:1<6::AID-MRD2>3.0.CO;2-M","article-title":"Specific expression of soluble adenylyl cyclase in male germ cells","volume":"56","author":"Sinclair","year":"2000","journal-title":"Mol Reprod Dev"},{"key":"R15-20240829","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1038\/ki.2011.95","article-title":"Intracellular cAMP signaling by soluble adenylyl cyclase","volume":"79","author":"Tresguerres","year":"2011","journal-title":"Kidney Int"},{"key":"R16-20240829","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1083\/jcb.200311119","article-title":"Bicarbonate-responsive \u201csoluble\u201d adenylyl cyclase defines a nuclear cAMP microdomain","volume":"164","author":"Zippin","year":"2004","journal-title":"J Cell Biol"},{"key":"R17-20240829","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.5858\/arpa.2011-0617-OA","article-title":"Expression of soluble adenylyl cyclase in lentigo maligna: Use of \u0131mmunohistochemistry with anti\u2013soluble adenylyl cyclase antibody (R21) in diagnosis of lentigo maligna and assessment of margins","volume":"136","author":"Magro","year":"2012","journal-title":"Arch Pathol Lab Med"},{"key":"R18-20240829","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1096\/fj.02-0598fje","article-title":"Compartmentalization of bicarbonate-sensitive adenylyl cyclase in distinct signaling microdomains","volume":"17","author":"Zippin","year":"2003","journal-title":"FASEB J"},{"key":"R19-20240829","doi-asserted-by":"crossref","first-page":"2646","DOI":"10.1016\/j.bbadis.2014.06.034","article-title":"Role of soluble adenylyl cyclase in cell death and growth","volume":"1842","author":"Ladilov","year":"2014","journal-title":"Biochim Biophys Acta"},{"key":"R20-20240829","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1111\/ced.12730","article-title":"Expression of soluble adenylyl cyclase in acral melanomas","volume":"41","author":"Li","year":"2016","journal-title":"Clin Exp Dermatol"},{"key":"R21-20240829","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5070\/D3232033981","article-title":"Giant benign intradermal melanocytic nevus of rapid onset","volume":"23","author":"Coates","year":"2017","journal-title":"Dermatol Online J"},{"key":"R22-20240829","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1097\/DAD.0b013e31825d79b3","article-title":"Genital melanocytic nevus arising in a background of lichen sclerosus in a 7-year-old female: The diagnostic pitfall with malignant melanoma. A literature review","volume":"34","author":"Pinto","year":"2012","journal-title":"Am J Dermatopathol"},{"key":"R23-20240829","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/s12105-012-0386-z","article-title":"Oral atypical cellular blue nevus: An infiltrative melanocytic proliferation","volume":"7","author":"Shumway","year":"2013","journal-title":"Head and Neck Pathol"},{"key":"R24-20240829","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1097\/DAD.0000000000000074","article-title":"Soluble adenylyl cyclase antibody (R21) as a diagnostic adjunct in the evaluation of lentigo maligna margins during slow Mohs surgery","volume":"36","author":"Solky","year":"2014","journal-title":"Am J Dermatopathol"}],"container-title":["Indian Journal of Pathology and Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/ijpm.ijpm_1146_21","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:31:38Z","timestamp":1787067098000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/ijpm.ijpm_1146_21"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,3]]},"references-count":24,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023]]}},"URL":"https:\/\/doi.org\/10.4103\/ijpm.ijpm_1146_21","relation":{},"ISSN":["0377-4929","0974-5130"],"issn-type":[{"value":"0377-4929","type":"print"},{"value":"0974-5130","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,3]]},"assertion":[{"value":"2021-11-24","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-06","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}