An analysis of granulation patterns, MIB-1 proliferation indices and p53 expression in 101 patients with acromegaly.

Abstract

Despite the wide spectrum of adenoma behavior in patients with acromegaly, the ability of most pathological markers to predict clinical and radiological behavior remains controversial. The authors sought to comprehensively examine clinical and radiological correlates of growth hormone (GH)-secreting pituitary adenomas with regard to several commonly used immunocytochemical techniques in patients undergoing transsphenoidal surgery for acromegaly. We performed a retrospective review of histopathological findings in 101 surgically resected GH adenomas. Tumors were assessed radiologically for different patterns of extension. Each tumor specimen was subject to immunocytochemical analysis, including assessments of granulation patterns, MIB-1 labeling indices, prolactin cosecretion, p53 expression and mitotic activity. Endocrinological outcome was assessed in 93 patients, with remission defined by the 2010 consensus criteria. Most tumors were macroadenomas and almost half were invasive. When compared to densely granulated tumors, sparsely granulated adenomas were associated with a younger age at presentation, higher preoperative IGF-1 levels, elevated MIB-1 index and pure GH immunostaining, but did not differ significantly in terms of extrasellar invasion or outcome. Increased mitotic activity and p53 expression were also associated with higher proliferation indices and a younger age at presentation. Mixed GH/prolactin tumors demonstrated significantly higher remission rates, independent of variations in extrasellar growth. MIB-1 indices did not correlate with the preoperative GH/IGF-1 levels, adenoma size or Knosp grade. The pathobiology of acromegaly is complex, and the clinicoradiological significance of subtyping on the basis of the markers employed in this study is debatable. Further investigation of newer molecular markers is warranted.