Adrenocorticotropic hormone secreting pituitary adenomas: Analysis of growth fraction using the MIB-1 antibody

Aims and background: Pituitary adenomas are usually considered well differentiated tumors, even if in about one third of cases they invade surrounding tissues, with the possibility of postoperative relapse after complete surgical removal. Adrenocorticotropic hormone (ACTH) secreting adenomas seem to be the most infiltrating subtype, with a higher incidence of recurrence. Ki-67 is a nuclear antigen which is easily detectable by means of the MIB-1 monoclonal antibody and the labeling index (LI) obtained can be considered a marker of tumor proliferation. Methods: In order to identify the growth fraction of these tumors we used the MIB-1 antibody to evaluate the expression of Ki-67 antibody in 11 ACTH secreting pituitary adenomas and to compare it with the LI obtained in 98 other hormone secreting or non-functioning pituitary adenomas consecutively operated on during a 40-month period. Results: In relation to surgically verified infiltration of the sellar floor dura and bone, we identified eight non-invasive and three invasive ACTH secreting pituitary adenomas. All invasive tumors infiltrated the wall of the cavernous sinus (CS). The mean Ki-67 LI was 5.88 +/- 9.13% versus 2.33 +/- 2.40% in non-ACTH secreting adenomas (P = 0.0025). It was 13.27 +/- 15.42% in invasive and 3.11 +/- 4.37% in non-invasive ACTH adenomas, and 18.40 +/- 17.82% in patients over 50 years versus 3.10 +/- 4.09% in younger subjects (P = 0.02). Conclusions: Ki-67 LI is a useful marker in the determination of proliferative activity and invasiveness of anterior pituitary adenomas, Our data seem to confirm that ACTH secreting adenomas have a higher growth fraction than other pituitary adenomas and this observation presumably explains the higher incidence of relapse of these tumors even after macroscopically total removal.