{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T18:32:59Z","timestamp":1789237979792,"version":"build-2803163510"},"reference-count":48,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,1,3]],"date-time":"2020-01-03T00:00:00Z","timestamp":1578009600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Primary Extra\u2010mammary Paget's disease (EMPD) is a very rare cutaneous adenocarcinoma affecting anogenital or axillary regions. It is characterized by a prolonged course with recurrences and eventually distant metastatic spread for which no specific therapy is known.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Eighteen EMPD (13 vulvar and five scrotal) and ten mammary Paget's disease (MPD) cases were comprehensively profiled for gene mutations, fusions and copy number alterations, and for therapy\u2010relevant protein biomarkers).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mutations in <jats:italic>TP53<\/jats:italic> and <jats:italic>PIK3CA<\/jats:italic> were the most frequent in both cohorts: 7\/15 and 5\/15 in EMPD; 1\/6 and 4\/7 in MPD <jats:italic>HER2<\/jats:italic> gene amplification was detected in 4\/18 EMPD (3 vulvar and 1 scrotal case) in contrast to MPD where it was detected in the majority (7\/8) of cases. <jats:italic>TOP2A<\/jats:italic> gene amplification was seen in 2\/12 EMPD and 1\/6 MPD, respectively. Similarly, no difference in estrogen receptor expression was seen between the EMPD (4\/15) and MPD (3\/10). Androgen receptor was also expressed in the majority of both cohorts (12\/16 EMPD) and (7\/8 MPD).Here <jats:italic>ARv7<\/jats:italic> splice variant was detected in 1\/7 EMPD and 1\/4 MPD cases, respectively. PD\u2010L1 expression on immune cells was exclusively observed in three vulvar EMPD. In contrast to MPD, six EMPDs harbored a \u201chigh\u201d tumor mutation burden (\u226510 mutations\/Mb). All tested cases from both cohorts were MSI stable.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>EMPD shares some targetable biomarkers with its mammary counterpart (steroid receptors, PIK3CA signaling pathways, <jats:italic>TOP2A<\/jats:italic> amplification). HER2 positivity is notably lower in EMPD while biomarkers to immune checkpoint inhibitors (high TMB and PD\u2010L1) were observed in some EMPD. Given that no consistent molecular alteration characterizes EMPD, comprehensive theranostic profiling is required to identify individual patients with targetable molecular alterations.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.2820","type":"journal-article","created":{"date-parts":[[2020,1,3]],"date-time":"2020-01-03T19:44:10Z","timestamp":1578080650000},"page":"1441-1450","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Comparison of the biomarkers for targeted therapies in primary extra\u2010mammary and mammary Paget's disease"],"prefix":"10.1002","volume":"9","author":[{"given":"Zoran","family":"Gatalica","sequence":"first","affiliation":[{"name":"Caris Life Sciences Phoenix AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9743-7265","authenticated-orcid":false,"given":"Semir","family":"Vranic","sequence":"additional","affiliation":[{"name":"College of 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