{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T09:09:01Z","timestamp":1788772141783,"version":"build-2803163510"},"reference-count":10,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Overexpression of brefeldin A-inhibited guanine nucleotide-exchange protein 3 (BIG3) has been reported in oestrogen receptor \u03b1-positive breast cancer (BC) tissues, with high BIG3 expression strongly associated with poor prognosis in patients with BC. This study investigated the expression pattern of BIG3 in patients with extramammary Paget disease (EMPD) and evaluated its clinical significance. Sixty-one tissue and 30 serum samples were collected from patients with EMPD. Immunohistochemistry showed that most EMPD tissues were positive for BIG3 (n = 57\/61, 93%), and strong BIG3 staining intensity correlated with the degree of invasiveness, lymph node or distant metastasis and overall survival. Serum BIG3 levels in patients with EMPD and invasive lesions were significantly higher than those in patients with in situ lesions and correlated with the serum concentration of cytokeratin 19 fragment. Therefore, BIG3 expression may serve as a prognostic marker in patients with EMPD.<\/jats:p>","DOI":"10.1093\/ced\/llag315","type":"journal-article","created":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T11:35:13Z","timestamp":1784460913000},"source":"Crossref","is-referenced-by-count":0,"title":["Overexpression of brefeldin A-inhibited guanine nucleotide-exchange protein 3 in patients with extramammary Paget disease"],"prefix":"10.1093","author":[{"given":"Tomofumi","family":"Kiyotoh","sequence":"first","affiliation":[{"name":"Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University , Kumamoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1697-9316","authenticated-orcid":false,"given":"Soichiro","family":"Sawamura","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University , Kumamoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tselmeg Mijiddorj","family":"Myangat","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University , Kumamoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8900-3520","authenticated-orcid":false,"given":"Shuichi","family":"Shimada","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University , Kumamoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiro","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University , Kumamoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayo","family":"Kashiwada-Nakamura","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University , Kumamoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikko","family":"Kajihara","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University , Kumamoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsunari","family":"Makino","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University , Kumamoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichi","family":"Masuguchi","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University , Kumamoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Fukushima","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University , Kumamoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"2026090704220489400_llag315-B1","first-page":"313","article-title":"Extramammary Paget\u2019s disease: treatment, prognostic factors and outcome in 76 patients","volume":"158","author":"Hatta","year":"2008","journal-title":"Br J Dermatol"},{"key":"2026090704220489400_llag315-B2","first-page":"797","article-title":"Genome-wide gene-expression profiles of breast-cancer cells purified with laser microbeam microdissection: identification of genes associated with progression and 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cells","volume":"8","author":"Yoshimaru","year":"2017","journal-title":"Nat Commun"},{"key":"2026090704220489400_llag315-B6","doi-asserted-by":"crossref","first-page":"oyaf235","DOI":"10.1093\/oncolo\/oyaf235","article-title":"Clinical and molecular landscape of metastatic extramammary Paget\u2019s disease","volume":"30","author":"Watanabe","year":"2025","journal-title":"Oncologist"},{"key":"2026090704220489400_llag315-B7","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1111\/1346-8138.13760","article-title":"Serum cytokeratin 19 fragment 21-1 is a useful tumor marker for the assessment of extramammary Paget\u2019s disease","volume":"44","author":"Kato","year":"2017","journal-title":"J Dermatol"},{"key":"2026090704220489400_llag315-B8","doi-asserted-by":"crossref","first-page":"4208","DOI":"10.1111\/cas.15099","article-title":"The survival and proliferation of osteosarcoma cells are dependent on the mitochondrial BIG3-PHB2 complex formation","volume":"112","author":"Toki","year":"2021","journal-title":"Cancer Sci"},{"key":"2026090704220489400_llag315-B9","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1038\/s41598-017-01951-6","article-title":"Stapled BIG3 helical peptide ERAP potentiates anti-tumour activity for breast cancer therapeutics","volume":"7","author":"Yoshimaru","year":"2017","journal-title":"Sci Rep"},{"key":"2026090704220489400_llag315-B10","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1309\/P756-XXCB-TV71-U4XV","article-title":"Extramammary Paget disease is characterized by the consistent lack of estrogen and progesterone receptors but frequently expresses androgen receptor","volume":"113","author":"Diaz de Leon","year":"2000","journal-title":"Am J Clin Pathol"}],"container-title":["Clinical and Experimental 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