title: Cell proliferation parameters and apoptosis indices in pituitary macroadenomas.
abstract: BACKGROUND
  Pituitary adenomas are usually well-differentiated tumors but may show locally aggressive behavior.
  
  
  OBJECTIVE
  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).
  
  
  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.
authors: Section of Endocrinology, Department of Medicine and Pharmacology, University of Messina, Messina, 98125, Italy.
authors: R M
authors: RM
authors: Ruggeri
authors: G
authors: G
authors: Costa
authors: A
authors: A
authors: Simone
authors: A
authors: A
authors: Campennì
authors: A
authors: A
authors: Sindoni
authors: A
authors: A
authors: Ieni
authors: V
authors: V
authors: Cavallari
authors: F
authors: F
authors: Trimarchi
authors: L
authors: L
authors: Curtò
mesh_terms: D000236:Adenoma / Q000378:metabolism / Q000473:pathology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002453:Cell Cycle; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008940:Mitotic Index; D010911:Pituitary Neoplasms / Q000378:metabolism / Q000473:pathology*; D011003:Ploidies; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; C513496:MIB1 ligase, human; D044767:Ubiquitin-Protein Ligases