{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T02:49:52Z","timestamp":1786589392667,"version":"build-2736575974"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,9,1]]},"abstract":"<jats:sec>\n<jats:title>Objective<\/jats:title>\n<jats:p>The aim of this study was to develop an open-source and reproducible digital quantitative analysis (DIA) of somatostatin receptor subtype 2a (SST<jats:sub>2<\/jats:sub>) staining in formalin-fixed paraffin-embedded tissues of pancreatic neuroendocrine tumors (panNETs) and growth hormone (GH)-secreting pituitary adenomas (GHomas).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Design<\/jats:title>\n<jats:p>SST<jats:sub>2<\/jats:sub> immunostaining of 18 panNETs and 39 GHomas was assessed using a novel DIA protocol and compared with a widely used semi-quantitative immunoreactivity score (IRS).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>The DIA software calculates the staining intensity\/area and the percentage of positive cells (%PC). Four representative images were selected for each sample by two independent selectors (S<jats:sub>1<\/jats:sub> and S<jats:sub>2<\/jats:sub>), with the analysis performed by two independent analyzers (A<jats:sub>1<\/jats:sub> and A<jats:sub>2<\/jats:sub>). Agreement between observers was calculated using the concordance correlation coefficient (CCC).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>In panNETs, the CCC ranged 0.935\u20130.977 for intensity\/area and 0.942\u20130.983 for %PC. In GHomas, the CCC ranged 0.963\u20130.997 for intensity\/area and 0.979\u20130.990 for %PC. In both panNETs and GHomas, the DIA staining intensity was strongly correlated with the IRS (Spearman rho: 0.916\u20130.969, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001), as well as the DIA %PC with the IRS %PC (Spearman rh: 0.826\u20130.881, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). In GHomas, the biochemical response to somatostatin receptor ligands correlated with SST<jats:sub>2<\/jats:sub> expression, evaluated both as DIA intensity\/area (Spearman rho: \u22120.448 to \u22120.527, <jats:italic>P<\/jats:italic>\u2009=\u20090.007\u20130.004) and DIA %PC (Spearman rho: \u22120.558 to \u22120.644, <jats:italic>P<\/jats:italic> \u2264 0.001).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>The DIA has an excellent inter-observer agreement and showed a strong correlation with the widely used semi-quantitative IRS. The DIA protocol is an open-source, highly reproducible tool and provides a reliable quantitative evaluation of SST<jats:sub>2<\/jats:sub> immunohistochemistry.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/eje-22-0339","type":"journal-article","created":{"date-parts":[[2022,7,4]],"date-time":"2022-07-04T09:47:17Z","timestamp":1656928037000},"page":"399-411","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-7","source":"Crossref","is-referenced-by-count":17,"title":["Digital quantification of somatostatin receptor subtype 2a immunostaining: a validation study"],"prefix":"10.1093","volume":"187","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4974-2075","authenticated-orcid":true,"given":"Claudia","family":"Campana","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands"},{"name":"Endocrinology Unit, Department of Internal Medicine and Medical Specialties, School of Medical and Pharmaceutical Sciences, University of Genova, Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter M","family":"van Koetsveld","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A","family":"Feelders","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wouter W","family":"de Herder","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anand M","family":"Iyer","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Louise F","family":"van Velthuysen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marije J","family":"Veenstra","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth S R","family":"van den Dungen","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanne E","family":"Franck","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Ferone","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Internal Medicine and Medical Specialties, School of Medical and Pharmaceutical Sciences, University of Genova, Genova, Italy"},{"name":"Endocrinology Unit, Department of Internal Medicine and Medical Specialties, School of Medical and Pharmaceutical Sciences, University of Genova, Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Gatto","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4897-2197","authenticated-orcid":true,"given":"Leo J","family":"Hofland","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","reference":[{"key":"bib1","series-title":"Pharmacological Reviews","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1124\/pr.117.015388","article-title":"International Union of Basic and Clinical Pharmacology. 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