title: Low cdc27 and high securin expression predict short survival for breast cancer patients.
abstract: Cell cycle regulators cdc27 and securin participate in control of the mitotic checkpoint and survey the mitotic spindle to maintain chromosomal integrity. This is achieved by their functions in metaphase-anaphase transition, DNA damage repair, enhancement of mitotic arrest and apoptosis. We report on the roles of cdc27 and securin in aneuploidy and prognosis of breast cancer. The study comprises 429 breast cancer patients with up to 22 years of follow-up. DNA content was determined by image cytometry, and immunopositivity for cdc27 and securin was based on tissue microarrays. An inverse association between cdc27 and securin expression was observed in both image cytometric and immunohistochemical analyses. Low cdc27 and high securin expression identified patients with significant difference in disease outcome. Cdc27 and securin immunoexpression identified patients at risk of early cancer death within five years from diagnosis. In multivariate analysis, the combination of cdc27 and securin immunohistochemistry was the strongest predictor of cancer death after lymph node status. We demonstrate, for the first time in human breast cancer, the prognostic value of cdc27 and securin immunohistochemistry. Cdc27 and securin appear promising biomarkers for applications in predicting disease progression, prognostication of individual patients and potential in anti-mitotic drug development.
authors.affiliation: Department of Pathology, University Hospital of Turku, Turku, Finland.
authors.forename: Kati
authors.initials: K
authors.lastname: Talvinen
authors.forename: Henna
authors.initials: H
authors.lastname: Karra
authors.forename: Reino
authors.initials: R
authors.lastname: Pitkänen
authors.forename: Ilmari
authors.initials: I
authors.lastname: Ahonen
authors.forename: Marjukka
authors.initials: M
authors.lastname: Nykänen
authors.forename: Minnamaija
authors.initials: M
authors.lastname: Lintunen
authors.forename: Mirva
authors.initials: M
authors.lastname: Söderström
authors.forename: Teijo
authors.initials: T
authors.lastname: Kuopio
authors.forename: Pauliina
authors.initials: P
authors.lastname: Kronqvist
mesh_terms: D000328:Adult; D000368:Aged; D000782:Aneuploidy; D064191:Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D044584:Carcinoma, Ductal / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018275:Carcinoma, Lobular / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D011237:Predictive Value of Tests; D011379:Prognosis; D064249:Securin; D016019:Survival Analysis
chemical_list: D064191:Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome; D014408:Biomarkers, Tumor; C577366:CDC27 protein, human; D018797:Cell Cycle Proteins; D009363:Neoplasm Proteins; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human
keywords: Cdc27; aneuploidy; breast cancer; cell cycle; prognosis; securin