{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T12:01:54Z","timestamp":1774353714766,"version":"3.50.1"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T00:00:00Z","timestamp":1644192000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Somatostatin receptor 2 (SSTR2) has been shown to be expressed in a subset of neuroendocrine tumors and carcinomas and plays a role in imaging studies and guiding therapy. Patients with tumors expressing SSTR2 may be successfully treated with somatostatin inhibitors or radiolabeled somatostatin analogues. We studied SSTR2 expression in TET and correlated it with 68Ga-DOTATATE PET\/CT or 68Ga-DOTATATE PET\/MR results and treatment outcome. An institutional database of TET was searched for thymoma, thymic carcinoma, and thymic neuroendocrine tumor (TNET) with available resection specimens. Cases were subtyped (2021 WHO classification) and staged (8<jats:sup>th<\/jats:sup> AJCC\/UICC staging). A section was stained with anti-SSTR2 antibody (clone UMB1). Percent tumor cells with membranous staining was recorded if present in \u22651% of tumor cells. Medical records were searched for 68Ga-DOTATATE PET scans and treatment. Statistical analysis was performed. Eighty patients (1969-2021) with a median age of 61.3 years (range, 19.1-87.3) (37 males, 46.3%) had thymic carcinoma (N=33), TNET (N=7), or thymoma (N=40). SSTR2 expression was identified in 29 (of 80, 36.3%) TET including 2\/2 (100%) small cell carcinomas, 2\/5 (40.0%) atypical carcinoid tumors, 16\/23 (69.6%) squamous cell carcinomas, 2\/2 (100%) lymphoepithelial carcinomas, 1\/1 (100%) adenosquamous carcinoma, and 6\/40 (15.0%) thymomas. SSTR2 expression in \u226550% of tumor cells (vs 1-49%) was associated with younger age (p=0.023) and shorter recurrence\/metastasis-free survival (p=0.007). 68Ga-DOTATATE PET scans (N=9) revealed a Krenning score of 3 in patients with atypical carcinoid tumor, small cell carcinoma, and squamous cell carcinoma (N=1 each) with SSTR2 expression in 95, 100, and 5% of tumor cells, respectively. Scans with Krenning scores of \u22642 (N=5) were seen in tumors with no SSTR2 expression in 80% of cases and a single atypical carcinoid tumor with SSTR2 expression in 10% of tumor cells. One scan resulted as \u201cincreased uptake\u201d was in a patient with no SSTR2 expression. In conclusion, 68Ga-DOTATATE PET scans correlated with SSTR2 expression in TET in most patients and appeared to be useful to identify patients with TET who may be amenable to treatment with somatostatin analogues. Larger studies including more patients with 68Ga-DOTATATE PET scans are necessary to independently and prospectively validate our findings.<\/jats:p>","DOI":"10.3389\/fonc.2022.823667","type":"journal-article","created":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T13:27:05Z","timestamp":1644240425000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["Correlation of Somatostatin Receptor 2 Expression, 68Ga-DOTATATE PET Scan and Octreotide Treatment in Thymic Epithelial Tumors"],"prefix":"10.3389","volume":"12","author":[{"given":"Anja C.","family":"Roden","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sagar","family":"Rakshit","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geoffrey B.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah M.","family":"Jenkins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aaron S.","family":"Mansfield","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2019.12.108","article-title":"Distribution of Mediastinal Lesions Across Multi-Institutional, International, Radiology Databases","volume":"15","author":"Roden","year":"2020","journal-title":"J Thorac Oncol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1093\/ejcts\/ezs529","article-title":"Clinicopathological Features of Thymic Carcinomas and the Impact of Histopathological Agreement on Prognostical Studies","volume":"43","author":"Roden","year":"2013","journal-title":"Eur J Cardiothorac Surg"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1093\/ejcts\/ezv239","article-title":"Long-Term Outcome and Prognostic Factors of Surgically Treated Thymic Carcinoma: Results of 306 Cases From a Japanese Nationwide Database Study","volume":"49","author":"Hishida","year":"2016","journal-title":"Eur J Cardiothorac Surg"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1093\/ejcts\/ezx037","article-title":"Comparison of Clinical Features and Survival Between Thymic Carcinoma and Thymic Carcinoid Patients","volume":"52","author":"Zhao","year":"2017","journal-title":"Eur J Cardiothorac Surg"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/his.13936","article-title":"A Mutation Analysis of the EGFR Pathway Genes, RAS, EGFR, PIK3CA, AKT1 and BRAF, and TP53 Gene in Thymic Carcinoma and Thymoma Type a\/B3","volume":"75","author":"Sakane","year":"2019","journal-title":"Histopathology"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1177\/1556984520949287","article-title":"Thymic Neuroendocrine Tumors and Thymic Carcinoma: Demographics, Treatment, and Survival","volume":"15","author":"Bakhos","year":"2020","journal-title":"Innovations (Phila)"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-021-03037-1","article-title":"Recent Advances and Conceptual Changes in the Classification of Neuroendocrine Tumors of the Thymus","volume":"478","author":"Bohnenberger","year":"2021","journal-title":"Virchows Arch"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2018.01.003","article-title":"The Integrated Genomic Landscape of Thymic Epithelial Tumors","volume":"33","author":"Radovich","year":"2018","journal-title":"Cancer Cell"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30062-7","article-title":"Pembrolizumab in Patients With Thymic Carcinoma: A Single-Arm, Single-Centre, Phase 2 Study","volume":"19","author":"Giaccone","year":"2018","journal-title":"Lancet Oncol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3016","article-title":"A Specific Missense Mutation in GTF2I Occurs at High Frequency in Thymic Epithelial Tumors","volume":"46","author":"Petrini","year":"2014","journal-title":"Nat Genet"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1136\/jclinpath-2020-207013","article-title":"Gene of the Month: GTF2I","volume":"74","author":"Nathany","year":"2021","journal-title":"J Clin Pathol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.lungcan.2016.12.005","article-title":"Analysis of a Panel of Druggable Gene Mutations and of ALK and PD-L1 Expression in a Series of Thymic Epithelial Tumors (TETs)","volume":"104","author":"Tiseo","year":"2017","journal-title":"Lung Cancer"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdr626","article-title":"Activating C-KIT Mutations in a Subset of Thymic Carcinoma and Response to Different C-KIT Inhibitors","volume":"23","author":"Schirosi","year":"2012","journal-title":"Ann Oncol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.2217\/fon.14.318","article-title":"Targeted Therapy for Thymic Epithelial Tumors: A New Horizon? Review of the Literature and Two Cases Reports","volume":"11","author":"Simonelli","year":"2015","journal-title":"Future Oncol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2017.01.028","article-title":"Loss of P16ink4a Expression and Homozygous CDKN2A Deletion Are Associated With Worse Outcome and Younger Age in Thymic Carcinomas","volume":"12","author":"Aesif","year":"2017","journal-title":"J Thorac Oncol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1007\/s12253-016-0144-8","article-title":"Molecular Profiling of Thymoma and Thymic Carcinoma: Genetic Differences and Potential Novel Therapeutic Targets","volume":"23","author":"Enkner","year":"2017","journal-title":"Pathol Oncol Res"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2015.03.003","article-title":"Immunohistochemical Status of PD-L1 in Thymoma and Thymic Carcinoma","volume":"88","author":"Katsuya","year":"2015","journal-title":"Lung Cancer"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.athoracsur.2015.10.044","article-title":"Clinicopathologic and Prognostic Implications of Programmed Death Ligand 1 Expression in Thymoma","volume":"101","author":"Yokoyama","year":"2016","journal-title":"Ann Thorac Surg"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1111\/his.13750","article-title":"Heterogeneity of Programmed Death-Ligand 1 Expression in Thymic Epithelial Tumours Between Initial Specimen and Synchronous or Metachronous Metastases or Recurrences","volume":"74","author":"Terra","year":"2019","journal-title":"Histopathology"},{"key":"B20","doi-asserted-by":"publisher","first-page":"6993","DOI":"10.18632\/oncotarget.24075","article-title":"A Comparative Study of PD-L1 Immunohistochemical Assays With Four Reliable Antibodies in Thymic Carcinoma","volume":"9","author":"Sakane","year":"2018","journal-title":"Oncotarget"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.31771","article-title":"Somatostatin Receptor 2 Signaling Promotes Growth and Tumor Survival in Small-Cell Lung Cancer","volume":"144","author":"Lehman","year":"2019","journal-title":"Int J Cancer"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.27107","article-title":"Amassion PP: Somatostatin Receptor 2 Targeting in Small Cell Lung Carcinoma: Perspectives","volume":"10","author":"Lehman","year":"2019","journal-title":"Oncotarget"},{"key":"B23","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1038\/s41467-020-20308-8","article-title":"Somatostatin Receptor 2 Expression in Nasopharyngeal Cancer is Induced by Epstein Barr Virus Infection: Impact on Prognosis, Imaging and Therapy","volume":"12","author":"Lechner","year":"2021","journal-title":"Nat Commun"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.115.161018","article-title":"68ga-DOTATATE PET\/CT in the Localization of Head and Neck Paragangliomas Compared With Other Functional Imaging Modalities and CT\/MRI","volume":"57","author":"Janssen","year":"2016","journal-title":"J Nucl Med"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinimag.2019.04.006","article-title":"Molecular Imaging and Therapy of Somatostatin Receptor Positive Tumors","volume":"56","author":"Ivanidze","year":"2019","journal-title":"Clin Imaging"},{"key":"B26","doi-asserted-by":"publisher","first-page":"e219009","DOI":"10.1148\/rycan.2021219009","article-title":"Somatostatin Receptor Type 2 as an Imaging and Treatment Target for Thyroid Cancer","volume":"3","author":"Boettcher","year":"2021","journal-title":"Radiol Imaging Cancer"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20123049","article-title":"Somatostatin Analogues in the Treatment of Neuroendocrine Tumors: Past, Present and Future","volume":"20","author":"Stueven","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-20-3453","article-title":"(177)Lu-DOTA-EB-TATE, a Radiolabeled Analogue of Somatostatin Receptor Type 2, for the Imaging and Treatment of Thyroid Cancer","volume":"27","author":"Thakur","year":"2021","journal-title":"Clin Cancer Res"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1316158","article-title":"Lanreotide in Metastatic Enteropancreatic Neuroendocrine Tumors","volume":"371","author":"Caplin","year":"2014","journal-title":"N Engl J Med"},{"key":"B30","doi-asserted-by":"publisher","first-page":"e0168215","DOI":"10.1371\/journal.pone.0168215","article-title":"Octreotide LAR and Prednisone as Neoadjuvant Treatment in Patients With Primary or Locally Recurrent Unresectable Thymic Tumors: A Phase II Study","volume":"11","author":"Kirzinger","year":"2016","journal-title":"PloS One"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.10374","article-title":"Somatostatin Analogs and Prednisone in Advanced Refractory Thymic Tumors","volume":"94","author":"Palmieri","year":"2002","journal-title":"Cancer"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.02.047","article-title":"Octreotide Alone or With Prednisone in Patients With Advanced Thymoma and Thymic Carcinoma: An Eastern Cooperative Oncology Group Phase II Trial","volume":"22","author":"Loehrer","year":"2004","journal-title":"J Clin Oncol"},{"key":"B33","volume-title":"WHO Classification of Tumours 5ed","year":"2021"},{"key":"B34","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-319-40618-3","volume-title":"AJCC Cancer Staging Manual","author":"Amin","year":"2017"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.3800954","article-title":"Somatostatin Receptor Type 2a Immunohistochemistry in Neuroendocrine Tumors: A Proposal of Scoring System Correlated With Somatostatin Receptor Scintigraphy","volume":"20","author":"Volante","year":"2007","journal-title":"Mod Pathol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19860315)57:6<1101::AID-CNCR2820570606>3.0.CO;2-A","article-title":"Chemotherapy of Malignant Thymoma. Case Report and Review of the Literature","volume":"57","author":"Hu","year":"1986","journal-title":"Cancer"},{"key":"B37","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.humpath.2021.08.004","article-title":"Somatostatin Receptor 2 is Highly Sensitive and Specific for Epstein-Barr Virus-Associated Nasopharyngeal Carcinoma","volume":"117","author":"Viswanathan","year":"2021","journal-title":"Hum Pathol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1097\/RLU.0000000000003857","article-title":"68ga-DOTATATE PET\/CT in Primary Pulmonary Lymphoepithelioma-Like Carcinoma","author":"Shang","year":"2021","journal-title":"Clin Nucl Med"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.3892\/etm.2021.10613","article-title":"The New WHO Classification of Gastrointestinal Neuroendocrine Tumors and Immunohistochemical Expression of Somatostatin Receptor 2 and 5","volume":"22","author":"Popa","year":"2021","journal-title":"Exp Ther Med"},{"key":"B40","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1007\/s00259-008-0944-5","article-title":"Correlation of Immunohistopathological Expression of Somatostatin Receptor 2 With Standardised Uptake Values in 68Ga-DOTATOC PET\/Ct","volume":"36","author":"Miederer","year":"2009","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdp334","article-title":"Somatostatin Receptor Tissue Distribution in Lung Neuroendocrine Tumours: A Clinicopathologic and Immunohistochemical Study of 218 \u2018Clinically Aggressive\u2019 Cases","volume":"21","author":"Righi","year":"2010","journal-title":"Ann Oncol"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2022.823667\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T13:27:09Z","timestamp":1644240429000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2022.823667\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,7]]},"references-count":41,"alternative-id":["10.3389\/fonc.2022.823667"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2022.823667","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,7]]},"article-number":"823667"}}