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Expression of MSX2 predicts malignancy of branch duct intraductal papillary mucinous neoplasm of the pancreas

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

To distinguish malignant from benign branch duct (BD)-intraductal papillary mucinous neoplasm (IPMN) still remains difficult. Recently, we revealed that MSX2 was frequently expressed in pancreatic cancer and its expression was correlated with aggressive behavior of the cancer. The aim of this study was to assess the involvement of MSX2 in IPMN development and whether its expression would differentiate malignant from benign IPMN.

Methods

Seventeen microdissected lesions and 45 IPMN tissues were used for quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry, respectively. The role of MSX2 in the pancreatic duct cell was assessed by the induced expression of MSX2 in a normal human pancreatic duct epithelial cell line (HPDE).

Results

Malignant IPMN expressed significantly higher levels of MSX2 mRNA than benign IPMN lesions. MSX2 protein expression was frequently found in borderline and malignant lesions (20/29, 68.9%), while its expression was seen in only one of 16 benign IPMN tissues. Univariate analysis showed that nodules of 6 mm or more and MSX2 expression were significantly correlated with the malignancy of BD-IPMN (P = 0.022 and 0.0026, respectively), and multivariate analysis revealed that only MSX2 expression was identified as an independent factor to predict malignant BD-IPMN. HPDE cells expressing MSX2 showed increased cellular proliferation compared to control cells.

Conclusions

Based on our results, MSX2 plays a pivotal role in the development of IPMN through growth stimulation of tumor cells, and its expression was identified as an independent predictive factor for malignancy of BD-IPMN.

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Abbreviations

IPMN:

Intraductal papillary-mucinous tumor of the pancreas

QRT-PCR:

Quantitative real-time reverse transcription-polymerase chain reaction

IPMA:

Intraductal papillary-mucinous adenoma

IPMB:

Borderline intraductal papillary-mucinous neoplasm

IPMC:

Intraductal papillary-mucinous carcinoma

IC-IPMN:

Invasive carcinoma derived from intraductal papillary-mucinous carcinoma

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

PBS:

Phosphate-buffered saline

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Acknowledgments

We thank Dr. M.S. Tsao for providing HPDE cells. This work was supported in part by Grants-in-Aid #21590870 and #20390202 from the Ministry of Education, Science, Sports and Culture in Japan.

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Authors and Affiliations

  1. Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aobaku, Sendai, Miyagi, 980-8574, Japan

    Kennichi Satoh, Shin Hamada, Atsushi Kanno, Morihisa Hirota, Jun Umino, Hiromichi Ito, Atsushi Masamune & Tooru Shimosegawa

  2. Division of Hepato-Biliary-Pancreatic Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aobaku, Sendai, Miyagi, 980-8574, Japan

    Shinichi Egawa & Michiaki Unno

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  1. Kennichi Satoh
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Correspondence to Kennichi Satoh.

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Satoh, K., Hamada, S., Kanno, A. et al. Expression of MSX2 predicts malignancy of branch duct intraductal papillary mucinous neoplasm of the pancreas. J Gastroenterol 45, 763–770 (2010). https://doi.org/10.1007/s00535-010-0200-1

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