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Distinct pathways of pathogenesis of intraductal oncocytic papillary neoplasms and intraductal papillary mucinous neoplasms of the pancreas

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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.

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Acknowledgments

The authors thank Ms. Tanisha Daniel for her assistance during manuscript preparation and Allyne Manzo and Lorraine Corsale for their assistance with the figures.

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  1. Sun M. Chung

    Present address: Montefiore Medical Center, Bronx, NY, USA

Authors and Affiliations

  1. Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10021, USA

    Olca Basturk, Gokce Askan, Christine Iacobuzio-Donahue, Jinru Shia & David S. Klimstra

  2. Department of Pathology, Weill Medical College of Cornell University, New York, NY, USA

    Sun M. Chung

  3. Department of Pathology, Johns Hopkins University Hospitals, Baltimore, MD, USA

    Ralph H. Hruban

  4. Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA

    N. Volkan Adsay, Serdar Balci & Bahar Memis

  5. Department of Pathology, Stony Brook Medicine, Stony Brook, NY, USA

    Sui Y. Zee

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  1. Olca Basturk
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The study was performed with approval of the Institutional Review Board and in accordance with Health Insurance Portability and Accountability Act regulations.

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This work has been supported by the Cancer Center Support Grant (CCSG)/Core Grant/P30 CA008748.

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Basturk, O., Chung, S.M., Hruban, R.H. et al. Distinct pathways of pathogenesis of intraductal oncocytic papillary neoplasms and intraductal papillary mucinous neoplasms of the pancreas. Virchows Arch 469, 523–532 (2016). https://doi.org/10.1007/s00428-016-2014-x

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