Proliferative Activity and Invasiveness among Pituitary Adenomas and Carcinomas: An Analysis Using the MIB-1 Antibody

Abstract

Although histologically benign, one-third of all pituitary tumors will be invasive of surrounding structures. In this study, the relationship between the proliferative activity in pituitary adenomas and their invasiveness was investigated. Invasion was defined as gross, operatively or radiologically apparent infiltration of dura or bone. Using the recently developed MIB-1 monoclonal antibody, which recognizes the Ki-67 cell cycle-specific nuclear antigen, the growth fractions of 37 noninvasive adenomas, 33 invasive adenomas, and 7 primary pituitary carcinomas were determined. All tumors were fully classified by histology, immunohistochemistry, and electron microscopy. The mean Ki-67 -derived growth fractions for noninvasive adenomas, invasive adenomas, and pituitary carcinomas were 1.37 +/- 0.15%, 4.66 +/- 0.57%, and 11.91 +/- 3.41%, respectively (mean +/- standard error of the mean). An analysis of variance and then individual pairwise comparisons confirmed significant differences in the mean Ki-67 labeling index between each of the three tumor groups (P < 0.01). The mean growth fraction of hormonally active pituitary adenomas (3.25 +/- 0.26%) was significantly higher than that for nonfunctioning adenomas (2.06 +/- 0.23%) (P = 0.03). Establishing a threshold labeling index of 3% served to distinguish invasive from noninvasive adenomas with 97% specificity and 73% sensitivity and was associated with positive and negative predictive values of 96 and 80%, respectively. Although invasive pituitary tumors exhibited significantly higher growth fractions than did noninvasive tumors, there were individual exceptions, indicating that in a subpopulation of invasive pituitary tumors, factors other than proliferative activity determine invasive potential.

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

“…Other studies confirmed the validity of comparative results with all antibodies cited (24). Since 1995, studies evaluating the MIB-1 monoclonal antibody in pituitary tumors have been reported in the literature (11,12,(25)(26)(27)(28)(29)(30)(31)(32)(33). In the studies by Knosp et al (15), Zhao et al (33) and Mastronardi et al (12), the mean positive reaction to Ki-67 was 1.1, 1.4, and 2.64%, respectively.…”

Cyclooxygenase‐2 expression in human pituitary tumors

“…Although previous studies have shown a correlation between cell proliferation marker expression and tumor aggressiveness, pituitary tumors generally grow slowly. 26,48 The lack of significant correlation between COX-2 expression and the presence of distant metastasis in pituitary tumors is not surprising. Similar results were reported with respect to colorectal carcinoma.…”

“…Details of immunohistochemistry, including the duration of exposure and control procedures for these three stains, as well as the morphometric quantification method have been described in previous publications. 25,26,32,33 Most tumors (n ϭ 119) were fixed in glutaraldehyde, routinely processed, embedded in Epon-Araldite, and studied by transmission electron microscopy.…”

“…22,23 Because the histologic appearance of pituitary tumors is a poor predictor of aggressive behavior, 24 a number of studies have assessed cell proliferation and angiogenesis markers as predictors of tumor prognosis. [25][26][27][28][29] To obtain deeper insight into the role of COX-2 in pituitary tumor pathobiology, we analyzed the correlation between COX-2 expression and immunolabeling for MIB-1, a cell proliferation marker, as well as microvessel density (MVD), microvessel surface density (MSD), and expression of hypoxia-inducible factor-1␣ (HIF-1␣).…”

Immunohistochemical Analysis of RCAS1 in Human Pituitary Adenomas

“…Some adenomas, however, grow rapidly despite their benign histologic features and invade the cavernous sinus (2,3). The histopathologic findings often do not predict the biologic behavior of these atypical tumors (4,5).…”