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).

FIGURE 1

Histopathological features of pituitary adenomas: (A) solid pattern (B) trabecular pattern (C) mixed pattern (D) papillary pattern (Hematoxylin and eosin staining, magnification ×20).

FIGURE 2

Cytoplasmic immunoreactivity for prolactin in pituitary adenoma samples (magnification ×40).

FIGURE 3

Immunostaining for Ki-67 antigen in pituitary adenoma samples. (A) Null cell adenoma (0% Ki-67 expression); (B) Prolactin (PRL)-secreting adenoma with 4.3% of Ki-67 expression; (C) PRL-secreting adenoma with 4.5% expression of Ki-67; (D) PRL-secreting adenoma with 6.6% expression of Ki-67.