Cell proliferation parameters and apoptosis indices in pituitary macroadenomas

J Endocrinol Invest. 2012 May;35(5):473-8. doi: 10.3275/7905. Epub 2011 Sep 6.


Background: Pituitary adenomas are usually well-differentiated tumors but may show locally aggressive behavior.

Aim: To investigate the relationship between proliferation and apoptosis parameters and tumor recurrence in a series of 20 radically resected pituitary macroadenomas (11 functioning, 9 non-functioning).

Materials and methods: Proliferative activity and DNA ploidy were analyzed by flow cytometry (FCM) on fresh surgical specimens. Immunohistochemistry for Ki-67/MIB-1 and for the anti-apoptotic protein Bcl-2 was performed on paraffin-embedded specimens from the same tumors. Tumor regrowth was evaluated by magnetic resonance imaging (MRI).

Results: Six adenomas recurred after surgery, regardless of hormonal hypersecretion. Pre-surgical tumor size was significantly higher in recurrent than in non-recurrent adenomas (p=0.003). Pre-surgical MRI demonstrated cavernous sinus (CS) invasiveness in all recurrent tumors, while none of the non-invasive adenomas recurred (p=0.042, by Fisher's exact test). The DNA content was aneuploid in 5/20 adenomas, one of which recurred. Cell percentages in the S (%SPF) and G2+M (%G2-M) phases and proliferative index (PI) (PI=%SPF+%G2-M) were significantly higher in aneuploid than in diploid adenomas (p<0.05), but no significant differences concerning all FCM parameters were observed between recurrent and non-recurrent adenomas. Similarly, MIB-1 did not show a significant difference of expression between recurrent and non-recurrent adenomas (p=0.33). Bcl-2 immunoreactivity was detected in 12/15 pituitary adenomas, involving 63±35% of tumor cells, regardless of tumor recurrence.

Conclusions: In this group of radically resected pituitary macroadenomas, neuroradiological finding of CS invasiveness--but not FCM parameters nor MIB-1 and Bcl-2 expression--is useful for predicting tumor recurrence.

MeSH terms

  • Adenoma / metabolism
  • Adenoma / pathology*
  • Adolescent
  • Adult
  • Aged
  • Apoptosis*
  • Biomarkers, Tumor / metabolism*
  • Cell Cycle
  • Cell Proliferation*
  • Female
  • Flow Cytometry
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • Ki-67 Antigen / metabolism
  • Male
  • Middle Aged
  • Mitotic Index
  • Pituitary Neoplasms / metabolism
  • Pituitary Neoplasms / pathology*
  • Ploidies
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Ubiquitin-Protein Ligases / metabolism
  • Young Adult


  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Proto-Oncogene Proteins c-bcl-2
  • MIB1 ligase, human
  • Ubiquitin-Protein Ligases