Molecular Evidence for Monoclonal Skip Progression in Main Duct Intraductal Papillary Mucinous Neoplasms of the Pancreas

Kenjiro Date, Takao Ohtsuka, Takaaki Fujimoto, Koji Tamura, Hideyo Kimura, Taketo Matsunaga, Naoki Mochidome, Tetsuyuki Miyazaki, Yasuhisa Mori, Yoshinao Oda, Masafumi Nakamura, Masao Tanaka

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10 Citations (Scopus)

Abstract

Objective: To clarify clonality of distinct multisegmental main duct (MD)-intraductal papillary mucinous neoplasms (IPMNs) using microarray analysis. Background: IPMNs represent a pancreatic ductal cell field defect, which causes multiple occurrences of lesions. In addtion, it has been speculated that MD-IPMNs display features of monoclonal skip progression. Methods: Total RNA was extracted from fresh-frozen tissue samples of metachronous MD-IPMNs and nonneoplastic pancreas tissue from the same pancreas from two individuals, and whole human genome microarray analysis was performed. Formalin-fixed paraffin-embedded tissue specimens from 28 distinct IPMNs were then collected from 12 patients, genomic DNA was extracted, and GNAS/KRAS mutational status was investigated. Immunohistochemical analysis was performed to validate the expression pattern of the indicated proteins. Results: Microarray analysis revealed that metachronous MD-IPMNs from the same individual displayed pair-wise correlation coefficients of 0.9523 and 0.9512. In contrast, MD-IPMNs of the same histological grade from different individuals displayed coefficients of 0.8092 and 0.8211. Scatter plot analysis revealed that metachronous MD-IPMNs from the same individual displayed a closer linear relationship. Furthermore, heat map and hierarchical cluster analyses revealed that metachronous MD-IPMNs from the same individual were classified in the same branch, and the gene expression patterns were similar. The GNAS/KRAS mutational statuses of distinct MD-IPMNs were consistent with each other. Immunohistochemical assessment of five specific proteins demonstrated that the same expression pattern between two lesions was observed in 95% of the samples. Conclusions: These findings using molecular analyses indicate that MD-IPMNs might display features of monoclonal skip progression.

Original languageEnglish
Pages (from-to)969-977
Number of pages9
JournalAnnals of surgery
Volume265
Issue number5
DOIs
Publication statusPublished - May 1 2017

All Science Journal Classification (ASJC) codes

  • Surgery

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    Date, K., Ohtsuka, T., Fujimoto, T., Tamura, K., Kimura, H., Matsunaga, T., Mochidome, N., Miyazaki, T., Mori, Y., Oda, Y., Nakamura, M., & Tanaka, M. (2017). Molecular Evidence for Monoclonal Skip Progression in Main Duct Intraductal Papillary Mucinous Neoplasms of the Pancreas. Annals of surgery, 265(5), 969-977. https://doi.org/10.1097/SLA.0000000000001755