PMID- 29420353 OWN - NLM STAT- MEDLINE DCOM- 20180824 LR - 20240315 IS - 1533-4058 (Electronic) IS - 1541-2016 (Print) IS - 1533-4058 (Linking) VI - 26 IP - 2 DP - 2018 Feb TI - Clusterin in Neuroendocrine Epithelial Neoplasms: Absence of Expression in a Well-differentiated Tumor Suggests a Jejunoileal Origin. PG - 94-100 LID - 10.1097/PAI.0000000000000563 [doi] AB - Clusterin, a widely expressed, tissue-specific glycoprotein, is a diagnostic marker of several tumor types, including anaplastic large cell lymphoma, follicular dendritic cell sarcoma, and tenosynovial giant cell tumor. A recent study has suggested it is highly expressed by well-differentiated neuroendocrine tumors (NET) arising at most anatomic sites, with the exception of jejunoileal tumors, and that it is similarly not expressed by poorly differentiated neuroendocrine carcinomas (NEC). We sought to validate this result in a large cohort of NETs and NECs. Clusterin immunohistochemistry was performed on tissue microarrays of 255 NETs [45 lung, 4 stomach, 8 duodenum, 75 pancreas (62 primary, 13 metastatic), 107 jejunoileum (69 primary, 38 metastatic), 16 appendix] and 88 NECs (43 visceral, 45 Merkel cell). Extent (%) and intensity (0, 1+, 2+, 3+) of staining were assessed and an H-score (extent x intensity) calculated. An average H-score >5 was considered positive. Clusterin expression was noted in 82.4% of 148 nonjejunoileal NETs (average H-score 183) and only 8.4% of 107 jejunoileal NETs (average H-score, 31), as well as 19.3% of NECs (average H-score, 36). Clusterin is frequently, strongly expressed by NETs of diverse anatomic sites, with the exception of jejunoileal tumors, in which it is only rarely, weakly expressed. It is occasionally, weakly expressed by NECs. Most metastatic NETs of occult origin arise in the pancreas or the jejunoileum. For cases in which an initial site of origin immunopanel (eg, islet 1, PAX6, CDX2) is ambiguous, addition of clusterin may be diagnostically useful, with absence of expression suggesting a jejunoileal origin. FAU - Czeczok, Thomas W AU - Czeczok TW AD - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN. FAU - Stashek, Kristen M AU - Stashek KM AD - Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA. FAU - Maxwell, Jessica E AU - Maxwell JE AD - Departments of Surgery. FAU - O'Dorisio, Thomas M AU - O'Dorisio TM AD - Internal Medicine. AD - Neuroendocrine Cancer Program, University of Iowa Health Care, Iowa City, IA. FAU - Howe, James R AU - Howe JR AD - Departments of Surgery. AD - Neuroendocrine Cancer Program, University of Iowa Health Care, Iowa City, IA. FAU - Hornick, Jason L AU - Hornick JL AD - Department of Pathology, Brigham and Women's Hospital, Boston, MA. FAU - Bellizzi, Andrew M AU - Bellizzi AM AD - Neuroendocrine Cancer Program, University of Iowa Health Care, Iowa City, IA. AD - Pathology. LA - eng GR - P50 CA174521/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - Appl Immunohistochem Mol Morphol JT - Applied immunohistochemistry & molecular morphology : AIMM JID - 100888796 RN - 0 (Biomarkers, Tumor) RN - 0 (Clusterin) SB - IM MH - Biomarkers, Tumor/*metabolism MH - Carcinoma, Neuroendocrine/diagnosis/*metabolism MH - Clusterin/*metabolism MH - Cohort Studies MH - Diagnosis, Differential MH - Humans MH - Immunohistochemistry MH - Jejunal Neoplasms/diagnosis/*metabolism MH - Neoplasms, Glandular and Epithelial/diagnosis/*metabolism MH - Neuroendocrine Tumors/diagnosis/*metabolism MH - Tissue Array Analysis PMC - PMC5808989 MID - NIHMS884542 COIS- Nothing To Disclose - The authors have indicated that they have no conflicts of interest that relate to the content of this manuscript. EDAT- 2018/02/09 06:00 MHDA- 2018/08/25 06:00 PMCR- 2019/02/01 CRDT- 2018/02/09 06:00 PHST- 2018/02/09 06:00 [entrez] PHST- 2018/02/09 06:00 [pubmed] PHST- 2018/08/25 06:00 [medline] PHST- 2019/02/01 00:00 [pmc-release] AID - 00129039-201802000-00002 [pii] AID - 10.1097/PAI.0000000000000563 [doi] PST - ppublish SO - Appl Immunohistochem Mol Morphol. 2018 Feb;26(2):94-100. doi: 10.1097/PAI.0000000000000563.