title: High cyclin E and low p27/Kip1 expressions are potentially poor prognostic factors in lung adenocarcinoma patients.
abstract: Cyclin E is an important regulator of entry into the S phase of the cell cycle. p27/Kip1 (p27) binds to cyclin E/Cdk2 complex and negatively regulates cell proliferation. We immunohistochemically examined the expression of cyclin E and p27 in 98 cases of resected lung adenocarcinoma to evaluate the prognostic significance of cyclin E and p27. Cyclin E was expressed in 16 cases (16%), and p27 was expressed in 41 cases (42%). Using Kaplan-Meier survival analysis, patients with cyclin E positive (P=0.0017) and p27 negative (P=0.011), both individually and in combination (P<0.0001), had a worse prognosis. We also analyzed the relationship of these findings to clinicopathological parameters, which revealed that cyclin E-positive, p27-negative cases had a higher Ki67 expression (P=0.012) and a higher rate of lymph node metastasis (P=0.0078) than other groups. Our results suggested that cyclin E over expression, in association with p27 reduction in particular, may potentially be a poor prognostic factor in lung adenocarcinoma patients. However, to verify the prognostic significance of these factors, a multivariate analysis of a larger number of patients should be undertaken.
authors.affiliation: Department of Pathology, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan. hirohaya@med.okoyama-cu.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Hayashi
authors.forename: N
authors.initials: N
authors.lastname: Ogawa
authors.forename: N
authors.initials: N
authors.lastname: Ishiwa
authors.forename: T
authors.initials: T
authors.lastname: Yazawa
authors.forename: Y
authors.initials: Y
authors.lastname: Inayama
authors.forename: T
authors.initials: T
authors.lastname: Ito
authors.forename: H
authors.initials: H
authors.lastname: Kitamura
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000096:biosynthesis*; D018797:Cell Cycle Proteins / Q000032:analysis / Q000096:biosynthesis*; D019927:Cyclin E / Q000032:analysis / Q000096:biosynthesis*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004791:Enzyme Inhibitors / Q000032:analysis*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D019927:Cyclin E; D004791:Enzyme Inhibitors; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27