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Distinct pathways of pathogenesis of intraductal oncocytic papillary neoplasms and intraductal papillary mucinous neoplasms of the pancreas.
Virchows Arch 2016; 469(5):523-532VA

Abstract

Intraductal oncocytic papillary neoplasm (IOPN) of the pancreas is classified as a variant of intraductal papillary mucinous neoplasm (IPMN) in the WHO guidelines. However, the neoplastic cells of IOPNs are unique, with distinctive architecture/oncocytic cytoplasm. Although molecular/immunohistochemical features of other IPMN variants have been extensively studied, those of IOPNs have not been well characterized. Expression profile of antibodies associated with genetic alterations previously described for ductal adenocarcinomas (DAs) and IPMNs (SMAD4/β-catenin/p53/mesothelin/claudin-4) as well as antibodies to mucins and differentiation markers [MUC1/MUC2/MUC5AC/MUC6/CDX2/hepatocyte paraffin-1 (HepPar-1)] was investigated in 24 IOPNs and 22 IPMNs to assess the similarities/differences between these tumors. Expression of mesothelin and claudin-4 was dissimilar between these tumor types: A higher proportion of IOPNs labeled with mesothelin [21/24 (87.5 %) of IOPNs, 6/22 (27 %) of IPMNs, p < 0.001], while the reverse was true for claudin-4 [2/23 (9 %) of IOPNs, 9/22 (41 %) of IPMNs, p = 0.01]. The results of immunolabeling for SMAD4/β-catenin/p53 were similar in both: None of the cases showed SMAD4 loss in the intraductal components, and only 1/21 (5 %) of IOPNs and 2/22 (9 %) of IPMNs revealed abnormal β-catenin expression (p = 0.49). Nuclear p53 accumulation was seen mostly in architecturally complex/high-grade dysplasia areas in both. Immunolabeling for MUC proteins showed that almost all lesions expressed MUC5AC. Twelve of the 24 (50 %) IOPNs and 6/22 (27 %) of IPMNs (p = 0.11) labeled for MUC1, whereas 7/24 (29 %) of IOPNs and 10/22 (45 %) of IPMNs labeled for MUC2 (p = 0.25). MUC6 was expressed in 8/9 (89 %) of IOPNs (strong) and 6/21 (29 %) of IPMNs (weak) (p = 0.002). Fourteen of the 23 (61 %) IOPNs and 4/22 (18 %) of IPMNs labeled for HepPar-1 (p = 0.003). These results show that IOPNs have distinct immunoprofile and provide support for the proposition that IOPN is a distinct entity developing through a mechanism different from other pancreatic ductal neoplasms.

Authors+Show Affiliations

Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10021, USA. basturko@mskcc.org.Department of Pathology, Weill Medical College of Cornell University, New York, NY, USA. Montefiore Medical Center, Bronx, NY, USA.Department of Pathology, Johns Hopkins University Hospitals, Baltimore, MD, USA.Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA.Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10021, USA.Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10021, USA.Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA.Department of Pathology, Stony Brook Medicine, Stony Brook, NY, USA.Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA.Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10021, USA.Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10021, USA. klimstrd@mskcc.org.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27591765

Citation

Basturk, Olca, et al. "Distinct Pathways of Pathogenesis of Intraductal Oncocytic Papillary Neoplasms and Intraductal Papillary Mucinous Neoplasms of the Pancreas." Virchows Archiv : an International Journal of Pathology, vol. 469, no. 5, 2016, pp. 523-532.
Basturk O, Chung SM, Hruban RH, et al. Distinct pathways of pathogenesis of intraductal oncocytic papillary neoplasms and intraductal papillary mucinous neoplasms of the pancreas. Virchows Arch. 2016;469(5):523-532.
Basturk, O., Chung, S. M., Hruban, R. H., Adsay, N. V., Askan, G., Iacobuzio-Donahue, C., ... Klimstra, D. S. (2016). Distinct pathways of pathogenesis of intraductal oncocytic papillary neoplasms and intraductal papillary mucinous neoplasms of the pancreas. Virchows Archiv : an International Journal of Pathology, 469(5), pp. 523-532.
Basturk O, et al. Distinct Pathways of Pathogenesis of Intraductal Oncocytic Papillary Neoplasms and Intraductal Papillary Mucinous Neoplasms of the Pancreas. Virchows Arch. 2016;469(5):523-532. PubMed PMID: 27591765.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Distinct pathways of pathogenesis of intraductal oncocytic papillary neoplasms and intraductal papillary mucinous neoplasms of the pancreas. AU - Basturk,Olca, AU - Chung,Sun M, AU - Hruban,Ralph H, AU - Adsay,N Volkan, AU - Askan,Gokce, AU - Iacobuzio-Donahue,Christine, AU - Balci,Serdar, AU - Zee,Sui Y, AU - Memis,Bahar, AU - Shia,Jinru, AU - Klimstra,David S, Y1 - 2016/09/03/ PY - 2016/07/21/received PY - 2016/08/29/accepted PY - 2016/08/16/revised PY - 2016/10/28/pubmed PY - 2017/2/16/medline PY - 2016/9/5/entrez KW - IOPN KW - IPMN KW - Immunohistochemistry KW - Oncocytic KW - Pancreas SP - 523 EP - 532 JF - Virchows Archiv : an international journal of pathology JO - Virchows Arch. VL - 469 IS - 5 N2 - Intraductal oncocytic papillary neoplasm (IOPN) of the pancreas is classified as a variant of intraductal papillary mucinous neoplasm (IPMN) in the WHO guidelines. However, the neoplastic cells of IOPNs are unique, with distinctive architecture/oncocytic cytoplasm. Although molecular/immunohistochemical features of other IPMN variants have been extensively studied, those of IOPNs have not been well characterized. Expression profile of antibodies associated with genetic alterations previously described for ductal adenocarcinomas (DAs) and IPMNs (SMAD4/β-catenin/p53/mesothelin/claudin-4) as well as antibodies to mucins and differentiation markers [MUC1/MUC2/MUC5AC/MUC6/CDX2/hepatocyte paraffin-1 (HepPar-1)] was investigated in 24 IOPNs and 22 IPMNs to assess the similarities/differences between these tumors. Expression of mesothelin and claudin-4 was dissimilar between these tumor types: A higher proportion of IOPNs labeled with mesothelin [21/24 (87.5 %) of IOPNs, 6/22 (27 %) of IPMNs, p < 0.001], while the reverse was true for claudin-4 [2/23 (9 %) of IOPNs, 9/22 (41 %) of IPMNs, p = 0.01]. The results of immunolabeling for SMAD4/β-catenin/p53 were similar in both: None of the cases showed SMAD4 loss in the intraductal components, and only 1/21 (5 %) of IOPNs and 2/22 (9 %) of IPMNs revealed abnormal β-catenin expression (p = 0.49). Nuclear p53 accumulation was seen mostly in architecturally complex/high-grade dysplasia areas in both. Immunolabeling for MUC proteins showed that almost all lesions expressed MUC5AC. Twelve of the 24 (50 %) IOPNs and 6/22 (27 %) of IPMNs (p = 0.11) labeled for MUC1, whereas 7/24 (29 %) of IOPNs and 10/22 (45 %) of IPMNs labeled for MUC2 (p = 0.25). MUC6 was expressed in 8/9 (89 %) of IOPNs (strong) and 6/21 (29 %) of IPMNs (weak) (p = 0.002). Fourteen of the 23 (61 %) IOPNs and 4/22 (18 %) of IPMNs labeled for HepPar-1 (p = 0.003). These results show that IOPNs have distinct immunoprofile and provide support for the proposition that IOPN is a distinct entity developing through a mechanism different from other pancreatic ductal neoplasms. SN - 1432-2307 UR - https://www.unboundmedicine.com/medline/citation/27591765/Distinct_pathways_of_pathogenesis_of_intraductal_oncocytic_papillary_neoplasms_and_intraductal_papillary_mucinous_neoplasms_of_the_pancreas_ L2 - https://dx.doi.org/10.1007/s00428-016-2014-x DB - PRIME DP - Unbound Medicine ER -