p16 and pRb immunohistochemical expression increases with increasing tumour grade in mammary phyllodes tumours

Histopathology. 2010 Jun;56(7):868-75. doi: 10.1111/j.1365-2559.2010.03562.x. Epub 2010 May 19.

Abstract

Aims: 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.

Methods and 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.

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Blotting, Western
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cyclin D1 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p16
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / metabolism
  • Neoplasm Proteins / metabolism*
  • Phyllodes Tumor / metabolism*
  • Phyllodes Tumor / pathology
  • Retinoblastoma Protein / metabolism*
  • Tissue Array Analysis

Substances

  • Biomarkers, Tumor
  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Ki-67 Antigen
  • Neoplasm Proteins
  • Retinoblastoma Protein
  • Cyclin D1