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

Aims and background: Pituitary adenomas are usually considered well differe ntiated tumors, even if in about one third of cases they invade surrounding tissues, with the possibility of postoperative relapse after complete surg ical removal. Adrenocorticotropic hormone (ACTH) secreting adenomas seem to be the most infiltrating subtype, with a higher incidence of recurrence. K i-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 t he MIB-1 antibody to evaluate the expression of Ki-67 antibody in 11 ACTH s ecreting pituitary adenomas and to compare it with the LI obtained in 98 ot her hormone secreting or non-functioning pituitary adenomas consecutively o perated on during a 40-month period. Results: In relation to surgically verified infiltration of the sellar floo r dura and bone, we identified eight non-invasive and three invasive ACTH s ecreting pituitary adenomas. All invasive tumors infiltrated the wall of th e 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 subjec ts (P = 0.02). Conclusions: Ki-67 LI is a useful marker in the determination of proliferat ive 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 high er incidence of relapse of these tumors even after macroscopically total re moval.