Measurement of Ki-67 antigen in 159 pituitary adenomas using the MIB-1 monoclonal antibody

Abstract

Pituitary adenomas sometimes show rapid growth and recurrence, and about one third invade the structures surrounding the sella turcica. In an attempt to determine aggressive behavior at an early stage, we used the MIB-1 antibody to identify the Ki-67 antigen. The present study was designed to evaluate pituitary adenomatous tissue in terms of secretion and proliferation and to correlate the Ki-67 index with hormone phenotype and invasive behavior. Material from 159 patients submitted to one or more resections of pituitary adenomas was evaluated. Forty-two non-secretory adenomas and 43 adenomas immunoreactive for growth hormone, 19 for prolactin, 18 for growth hormone and prolactin, 16 for adrenocorticotropic hormone (ACTH), and 21 cases of plurihormonal/gonadotropin adenomas were detected by immunohistochemistry. The MIB-1 antibody was positive in 139 samples and the Ki-67 index ranged from 0.16 to 15.48% (mean = 1.22 ± 2.09%), with no significant difference between genders, age groups, or secretory and non-secretory status. The Ki-67 index was higher in ACTH-secreting adenomas. Invasive pituitary adenomas had a significantly higher Ki-67 index (2.01 ± 3.15%) than macroadenomas with or without supra-sellar extension (1.12 ± 1.87%; P = 0.02). The index was not significantly different in the subgroup of adenomas with invasion of the cavernous sinus compared to groups with other types of invasion. We conclude that tumoral proliferative activity evaluated by the detection of the Ki-67 antigen is significantly higher in invasive than noninvasive adenomas, information which can be useful in therapeutic postoperative management since index cut-off values associated with aggressive behavior can be established.

Ki-67 Expression for Predicting Progression of Postoperative Residual Pituitary Adenomas: Correlations With Clinical Variables

“…20) Some studies also demonstrated a correlation between MIB-1 labeling index and re-growth or recurrence, 9,14,30,32) but other studies found no such correlations. 5,13,24,27) These discrepancies and differences between estimates of the threshold MIB-1 labeling index may be attributable to variations in the definition of recurrence or progression. 26) Another possible source of differences or discrepancies is the method used to count the labeled cells.…”

“…8,18) Various attempts have been made to establish markers that correlate with the clinical behavior of pituitary adenomas, such as invasion, recurrence, or malignancy. 1,2,5,[7][8][9][10][12][13][14][15]17,[19][20][21][22][23][24][27][28][29][30][31][32][33] Among the available methods of growth fraction determination, Ki-67 is a reliable marker for growth fraction determination of various specific cell cycle antigens. 1,12,32) Ki-67 is a protein which reacts with a …”

Pathohistological classification of pituitary tumors: 10 years of experience with the German Pituitary Tumor Registry

“…In contrast, the other types (ACTH cell adenomas in Nelson's syndrome, inactive ACTH cell adenomas, FSH/LH cell adenomas, and TSH cell adenomas) demonstrated invasion of surrounding structures in the majority of tumors investigated (82-100%; Table 3) (22). Invasive pituitary adenomas are generally characterized by a higher Ki-67 proliferation index (13,14). In addition, invasive adenomas may demonstrate p53-positive nuclei, which were found to be absent in enclosed adenomas (14,23,24).…”

Cavernous sinus invasion and effect of immunohistochemical features over remission in growth hormone secreting pituitary adenomas

“…Mastronardi et al examined 103 pituitary gland adenoma patients and found the Ki-67 proliferation index to be a useful marker for the invasion character of pituitary tumors (33). There are some other studies that support this study (21,22,26,40). Kawamato et al managed another study regarding the relationship between invasion and Ki-67 proliferation index and found no correlation (24).…”