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

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

研究成果: Contribution to journalArticle査読

8 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)163-169
ページ数7
ジャーナルVirchows Archiv
460
2
DOI
出版ステータス出版済み - 2 2012

All Science Journal Classification (ASJC) codes

  • 病理学および法医学
  • 分子生物学
  • 細胞生物学

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