title: p16 and pRb immunohistochemical expression increases with increasing tumour grade in mammary phyllodes tumours.
abstract: OBJECTIVE
  Control of cell cycling and proliferation is critical to the development of neoplasia and may play a role in the pathogenesis of phyllodes tumours (PTs). This study aimed to evaluate the immunohistochemical expression of certain proteins from the G(1)/S transition of the cell cycle in a cohort of PTs, to determine their role in tumour pathogenesis and to identify any associations with patient outcome.
  
  
  RESULTS
  Sixty-five PTs (34 benign, 23 borderline and eight malignant) diagnosed at a single institution between 1990 and 2006 were analysed. Immunohistochemistry for p16, pRb, cyclin D1 and Ki67 was performed. Expression of the following markers increased significantly with tumour grade: stromal nuclear and cytoplasmic p16 (P = 0.01 and 0.002, respectively), stromal and epithelial pRb (P = 0.000,000,06 and 0.004, respectively), and stromal and epithelial Ki67 (P = 0.03 and 0.04, respectively). Epithelial pRb scores of 7 (range 0-7) were significantly associated with reduced disease-free survival (DFS) compared with scores of <7 (P = 0.0009). No relationship was found between cyclin D1 expression in either the epithelium or the stroma, and grade or DFS.
  
  
  CONCLUSIONS
  The results suggest that alterations at the G(1)/S transition of the cell cycle play an important role in the progression of PTs.
authors.affiliation: Department of Anatomical Pathology, Royal Prince Alfred Hospital, Sydney, NSW, Australia. rooshdiya.karim@sswahs.nsw.gov.au
authors.forename: Rooshdiya Z
authors.initials: RZ
authors.lastname: Karim
authors.forename: Sebastien K
authors.initials: SK
authors.lastname: Gerega
authors.forename: Y H
authors.initials: YH
authors.lastname: Yang
authors.forename: Andrew
authors.initials: A
authors.lastname: Spillane
authors.forename: Hugh
authors.initials: H
authors.lastname: Carmalt
authors.forename: Richard A
authors.initials: RA
authors.lastname: Scolyer
authors.forename: C Soon
authors.initials: CS
authors.lastname: Lee
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D019938:Cyclin D1 / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D003557:Phyllodes Tumor / Q000378:metabolism* / Q000473:pathology; D016160:Retinoblastoma Protein / Q000378:metabolism*; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D016160:Retinoblastoma Protein; D019938:Cyclin D1