title: Correlation of enhanced cell turnover with prognosis of gastrointestinal stromal tumors of the stomach: relevance of cellularity and p27kip1.
abstract: The aim of the present study was to determine whether expression of molecules associated with cell cycle regulation and apoptosis might reflect tumor grade and patients' prognosis of gastrointestinal stromal tumor (GIST). Forty-nine cases of gastric GIST were divided into three grades; low, intermediate, and high risk. Ki-67, cyclin A, cyclin D1, cyclin E, p16(Ink4), p21(Waf1), p27(Kip1), cyclin-dependent kinase (cdk)2, cdk4 and single-strand DNA (ssDNA) were immunohistochemically stained and assessed. Ki-67, ssDNA, cyclin A and cdk2 had higher labeling indices (LI) in high-risk than in low-risk cases. Cyclin E expression was greater in the intermediate- than in the low-risk grade. On Kaplan-Meier analysis, tumor size, necrosis, cellularity, Ki-67, ssDNA, and cyclin A LI were significantly correlated with disease-free survival. Necrosis, cellularity, and Ki-67 LI were significant as prognostic factors on univariate, and Ki-67 LI on multivariate Cox hazard tests. Within the high-risk grade, high cellularity and low p27(Kip1) subgroups had the worst prognosis. The histological grade is related to cell turnover, assessed in terms of Ki-67, ssDNA, cyclin A, cyclin E, and cdk2 levels. Ki-67, ssDNA, and cyclin A are useful for prediction of prognosis, with cellularity and p27(Kip1) expression as further prognostic factors in high-risk cases.
authors.affiliation: Department of Surgery, School of Medicine, Kitasato University, Sagamihara, Japan. nemosurg@terra.dti.ne.jp
authors.forename: Yuta
authors.initials: Y
authors.lastname: Nemoto
authors.forename: Tetuo
authors.initials: T
authors.lastname: Mikami
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Hana
authors.forename: Shirou
authors.initials: S
authors.lastname: Kikuchi
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Isao
authors.initials: I
authors.lastname: Okayasu
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000502:physiology; D014408:Biomarkers, Tumor / Q000032:analysis*; D018797:Cell Cycle Proteins / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27