High Ki-67 expression is associated with prolactin secreting pituitary adenomas

Abstract

Pituitary adenomas represent the third most common primary intracranial tumor in neurosurgical practice. To understand the biological behaviour of the pituitary adenomas previous studies have determined the tumor proliferation rate using monoclonal antibodies targeted against the Ki-67 antigen. The aim of this study was to correlate the Ki-67 index with hormonal profiles of pituitary adenomas. The study included 50 pituitary adenomas. For histopathologic evaluation, the sections were stained with routine hematoxylin and eosin method. Additional paraffin sections from each tumor were immunostained using primary antibodies against the following pituitary hormones: somatotropin (STH), prolactin (PRL), adrenocorticotrophic hormone (ACTH), thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). To detect the expression of Ki-67 we used a mouse anti-human monoclonal antibody (clone K2). The percentage of Ki-67 positive nuclei (Ki-67 labeling index) was assessed by counting approximately 1000 nuclei of the tumor cells at ×400 magnification. Out of the 50 tumor samples, 31 (62%) pituitary adenomas showed proliferative activity, and the proliferation rate was variable in this group. The overall mean Ki-67 labeling index was 1.59 ± 1.47, ranging from 0.3% to 6.6%. In 5 cases, the Ki-67 index was >3%, all of them being prolactinomas. The Ki-67 index was higher in PRL-secreting adenomas (mean ± SD was 3.37 ± 1.80, range 0.9 - 6.6%). Our study provides the evidence that a higher Ki-67 value is associated with pituitary adenomas that secrete PRL (prolactinomas and mixed STH/PRL-secreting adenomas).

Comparison of Ki-67 index values between patients with operated giant prolactinomas and macroprolactinomas

“…12 On the contrary, Pizarro et al 22 argued that mitotic activity evaluated by the detection of Ki-67 antigen was significantly higher in invasive than in non-invasive pituitary adenomas and that Ki-67 could be used in therapeutic postoperative management since cut-off values associated with aggressive behavior of the tumor can be established. Băliniăteanu et al 23 reported higher Ki-67 values in prolactinomas secreting PRL. However, in our study we compared Kivalues between macroprolactinomas and giant prolactinomas for the first time in the literature and could not find a statistically significant difference between the two types of pituitary adenomas (31.06 vs 31.60, p=0.922).…”

Pimozide augments bromocriptine lethality in prolactinoma cells and in a xenograft model via the STAT5/cyclin D1 and STAT5/Bcl‑xL signaling pathways

“…Mechanistically, pimozide was effective in inhibiting STAT5 and its downstream effectors, cyclin D1 and Bcl-xL. Since cyclin D1 is a modulator of the cell cycle and Bcl-xL affects apoptosis ( 9 , 38 , 39 ), it was proposed that STAT5/cyclin D1 and STAT5/Bcl-xL may contribute to the antitumor effects of pimozide.…”