title: Cyclin D1 in invasive breast carcinoma: favourable prognostic significance in unselected patients and within subgroups with an aggressive phenotype.
abstract: OBJECTIVE
  To study the clinicopathological and prognostic value of cyclin D1 overexpression in patients with breast carcinoma.
  
  
  RESULTS
  Immunohistochemistry was performed on paraffin-embedded tissue specimens from 290 invasive breast carcinomas to detect the proteins cyclin D1, oestrogen receptor (ER), progesterone receptor (PR), p53, c-erbB2, and topoisomerase IIα (topoIIα). Cyclin D1 staining was quantified using a computerized image analysis method. Cyclin D1 overexpression characterized smaller, ER-positive and PR-positive tumours (P = 0.017, P < 0.0001, and P < 0.0001, respectively), of a lower histological and nuclear grade (P = 0.011 and P < 0.0001, respectively), and with reduced expression of topoIIα (P = 0.001) and p53 (P < 0.001). Cyclin D1 was found to have an independent favourable impact on the overall survival of both the unselected cohort of patients (P = 0.011) and of patients with ER-negative and lymph node-positive tumours (P = 0.034 and P = 0.015, respectively). In triple-negative tumours, cyclin D1 overexpression was found to have independent favourable impacts on both overall and relapse-free survival (P = 0.002 for both).
  
  
  CONCLUSIONS
  This is the first immunohistochemical study to dissociate the advantageous prognostic effect of cyclin D1 overexpression from its association with ER expression, and to provide evidence that cyclin D1 overexpression may be a marker of prolonged survival in patient subgroups with aggressive phenotypes.
authors.affiliation: 5th Department of Internal Medicine, Evagelismos Hospital, University of Athens, Athens, Greece.
authors.forename: Eleni
authors.initials: E
authors.lastname: Mylona
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Tzelepis
authors.forename: Irene
authors.initials: I
authors.lastname: Theohari
authors.forename: Ioanna
authors.initials: I
authors.lastname: Giannopoulou
authors.forename: Christos
authors.initials: C
authors.lastname: Papadimitriou
authors.forename: Lydia
authors.initials: L
authors.lastname: Nakopoulou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D019938:Cyclin D1 / Q000032:analysis / Q000096:biosynthesis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007150:Immunohistochemistry; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010641:Phenotype; D011379:Prognosis; D016016:Proportional Hazards Models; D011960:Receptors, Estrogen / Q000096:biosynthesis
chemical_list: D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D019938:Cyclin D1