Differential expression of cyclin D1 in human pituitary tumors: relation to MIB-1 and p27/Kip1 labeling indices

J Egypt Natl Canc Inst. 2011 Dec;23(4):171-9. doi: 10.1016/j.jnci.2011.11.003. Epub 2011 Dec 29.

Abstract

Background: Pituitary tumors are a common form of endocrine neoplasia. However few studies assessed the expression of the principal cyclin regulating checkpoint exit, cyclin D1. Cyclin D1 expression in pituitary tumors and its possible relation to MIB-1 and p27/Kip1 labeling indices (LIs) was explored.

Design: We studied a total of 199 pituitaries, including normal pituitaries (n=7), pituitary adenomas (n=187), and pituitary carcinoma (n=5). All tissues were tested as cores of archived tissue microarrays that were immunostained for cyclin D1, MIB-1 and p27 using a standard technique. Tissue cores were subjected to automated analysis to evaluate the staining LIs.

Results: No cyclin D1 positive cells in the normal anterior pituitary gland was found. Sparse nuclear staining was noted in pituitary tumors. Higher expression of cyclin D1 was noted in pituitary carcinomas compared to adenomas (p<0.001), in non-functioning adenomas compared to functioning ones (p<0.001) in macroadenomas versus microadenomas (p=0.017) and in recurrent non recurrent adenomas (p<0.001). Cyclin D1 LI and MIB-1 LI were related among adenomas (p<0.001) and carcinomas (p=0.041). p27 LI was neither related to pituitary adenoma recurrence nor invasion.

Conclusions: Expression of cyclin D1 in pituitary tumors is related to cell proliferation, recurrence, and metastatic potential. Nuclear cyclin D1 expression is a good marker of aggressive behavior in pituitary tumors.

MeSH terms

  • Adenoma / metabolism*
  • Adenoma / pathology
  • Adult
  • Carcinoma / metabolism*
  • Carcinoma / pathology
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism*
  • Female
  • Gene Expression
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / metabolism
  • Pituitary Neoplasms / metabolism*
  • Pituitary Neoplasms / pathology
  • ROC Curve
  • Tissue Array Analysis
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • CCND1 protein, human
  • CDKN1B protein, human
  • Cyclin D1
  • Cyclin-Dependent Kinase Inhibitor p27
  • MIB1 ligase, human
  • Ubiquitin-Protein Ligases