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Expression level of the mitotic checkpoint protein and G2–M cell cycle regulators and prognosis in gastrointestinal stromal tumors in the stomach

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Abstract

The biological behavior of gastrointestinal stromal tumors (GISTs) ranges from benign to malignant, and the risk of an adverse outcome is correlated with the location of the primary tumor, tumor size, and mitotic counts. Cell cycle regulators are potentially associated with the tumorigenesis and progression of GISTs. Checkpoint with forkhead and ring finger (CHFR) functions as an important checkpoint protein in the early to mid-prophase to regulate mitosis. In this study, we evaluated the expression of CHFR and several cell cycle regulators, including cyclin A, cyclin B1, cdc2, and cdk2, by immunohistochemical staining in 53 cases of primary gastric GISTs, and compared the immunohistochemical results with the clinicopathological factors or the GIST risk grades as modified by Miettinen et al. Of the 53 cases, 18 (34%) showed decreased nuclear CHFR expression. Decreased CHFR expression was correlated with higher mitotic counts [>5/50 high-power fields (HPFs)] (p = 0.039) and a high-risk grade (p = 0.0475), but not with expression of other cell cycle regulators. Higher cyclin A labeling index (LI, >1.5%), cyclin B1 LI (>0.25%), cdc2 LI (>1.16%), Ki-67 LI (>4.9%), mitotic counts (>5/50 HPF) and high-risk grade were each associated with shorter disease-free survival (p = 0.0017, p = 0.003, p = 0.0471, p = 0.002, p < 0.001, and p = 0.0017, respectively). Our results suggest that modified risk grade and increased expression of G2–M regulators such as cyclin A, cyclin B1, and cdc2 are useful for predicting the biological behavior of gastric GISTs. In addition, decreased CHFR expression may play a role in increased proliferative activity of higher grade GISTs.

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Acknowledgment

This study was supported in part by the Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science, Tokyo, Japan (Grant Number 22790346; H. Yamamoto).

Conflict of interest statement

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Aya Fujita, Hidetaka Yamamoto, Masakazu Imamura, Norimoto Nakamura, Masazumi Tsuneyoshi & Yoshinao Oda

  2. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Masakazu Imamura & Yoshihiko Maehara

Authors
  1. Aya Fujita
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  2. Hidetaka Yamamoto
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  3. Masakazu Imamura
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  4. Norimoto Nakamura
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  5. Yoshihiko Maehara
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  6. Masazumi Tsuneyoshi
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  7. Yoshinao Oda
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Correspondence to Yoshinao Oda.

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Fujita, A., Yamamoto, H., Imamura, M. et al. Expression level of the mitotic checkpoint protein and G2–M cell cycle regulators and prognosis in gastrointestinal stromal tumors in the stomach. Virchows Arch 460, 163–169 (2012). https://doi.org/10.1007/s00428-011-1181-z

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  • DOI: https://doi.org/10.1007/s00428-011-1181-z

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