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Mucinous cystic carcinoma of the pancreas: a unique cell line and xenograft model of a preinvasive lesion

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Abstract

Pancreatic mucinous cystic tumors (MCT) are proliferations of mucin-producing epithelia supported by an ovarian-like stroma. They are classified into adenomas (MCA), borderline (MCB) and noninvasive or invasive carcinomas (MCC). The molecular mechanisms underlying their clinical behavior are poorly understood, partly due to the lack of cellular models. We report the establishment of MCC1, the first cell line from a pancreatic MCT, deriving from the highly dysplastic cell component of a noninvasive MCC. MCC1 has mutations in codon 12 of K-RAS (GGT>GAT), codon 58 of P16 (CGA>TGA) and codon 132 of P53 (AAG>AGG). The FHIT and DPC4 genes are unaltered. Immunohistochemistry shows abnormal expression of MUC1 and p53, loss of p16 and retention of Fhit and Dpc4 in both the cell line and the highly dysplastic cells of the primary lesion. The morphological and molecular features of MCC1 and its corresponding primary tumor are consistent with a model for non-invasive MCC, where K-RAS, P16, P53 and MUC1 alterations are pre-invasive changes associated with progression of malignancy of MCT from adenoma to carcinoma. MCC1 is sensitive to 5-fluorouracil, representing the first assessment of drug sensitivity for MCC. Finally, MCC1 is a suitable model for preclinical studies, as it grows in immunodeficient mice.

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Acknowledgements

This work was supported by: Associazione Italiana Ricerca Cancro, Milan, Italy; Fondazione Cassa di Risparmio (Bando 2001), Verona, Italy; CNR-diagnostica molecolare, Ministero Università and Ministero Sanita’, Rome, Italy; and European Community Grant QLG1-CT-2002–01196.

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Authors and Affiliations

  1. Dipartimento di Patologia, Università di Verona, Strada Le Grazie 8, 37134 , Verona, Italy

    Claudio Sorio, Paola Capelli, Daniele Lissandrini, Patrick S. Moore, Giuseppe Zamboni & Aldo Scarpa

  2. Istituto di Anatomia Patologica, Università di Brescia, Italy

    Piera Balzarini

  3. Dipartimento di Scienze Chirurgiche e Gastroenterologiche, Università di Verona, Italy

    Massimo Falconi

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  1. Claudio Sorio
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  2. Paola Capelli
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  3. Daniele Lissandrini
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  4. Patrick S. Moore
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  5. Piera Balzarini
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  6. Massimo Falconi
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  7. Giuseppe Zamboni
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  8. Aldo Scarpa
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Correspondence to Aldo Scarpa.

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Sorio, C., Capelli, P., Lissandrini, D. et al. Mucinous cystic carcinoma of the pancreas: a unique cell line and xenograft model of a preinvasive lesion. Virchows Arch 446, 239–245 (2005). https://doi.org/10.1007/s00428-004-1167-1

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  • DOI: https://doi.org/10.1007/s00428-004-1167-1

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