{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T02:09:29Z","timestamp":1783649369761,"version":"3.55.0"},"reference-count":42,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,9,28]],"date-time":"2020-09-28T00:00:00Z","timestamp":1601251200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["APMIS"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:p>Neuroendocrine tumors (NETs) are often diagnosed from the metastases of an unknown primary tumor. Specific immunohistochemical (IHC) markers indicating the location of a primary tumor are needed. The proprotein convertase subtilisin\/kexin type 2 (PCSK2) is found in normal neural and neuroendocrine cells, and known to express in NETs. We investigated the tissue microarray (TMA) of 86 primary tumors from 13 different organs and 9 metastatic NETs, including primary tumor\u2010metastasis pairs, for PCSK2 expression with polymer\u2010based IHC. PCSK2 was strongly positive in all small intestine and appendiceal NETs, the so\u2010called midgut NETs, in most pheochromocytomas and paragangliomas, and in some of the typical and atypical pulmonary carcinoid tumors. NETs showing strong positivity were re\u2010evaluated in larger tumor cohorts confirming the primary observation. In the metastases, the expression of PCSK2 mirrored that of the corresponding primary tumors. We found negative or weak staining in NETs from the thymus, gastric mucosa, pancreas, rectum, thyroid, and parathyroid. PCSK2 expression did not correlate with Ki\u201067 in well\u2010differentiated NETs. Our data suggest that PCSK2 positivity can indicate the location of the primary tumor. Thus, PCSK2 could function in the IHC panel determined from screening metastatic NET biopsies of unknown primary origins.<\/jats:p>","DOI":"10.1111\/apm.13071","type":"journal-article","created":{"date-parts":[[2020,8,14]],"date-time":"2020-08-14T21:16:52Z","timestamp":1597439812000},"page":"563-572","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["PCSK2 expression in neuroendocrine tumors points to a midgut, pulmonary, or pheochromocytoma\u2013paraganglioma origin"],"prefix":"10.1111","volume":"128","author":[{"given":"Satu Maria","family":"Remes","sequence":"first","affiliation":[{"name":"Department of Pathology Helsinki University Hospital and HUSLAB University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Leijon","sequence":"additional","affiliation":[{"name":"Department of Pathology Helsinki University Hospital and HUSLAB University of Helsinki 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