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Prognostic Significance of the Ki-67 Labeling Index in Growth Hormone-Secreting Pituitary Adenomas

Section of Endocrinology (A.F., A.B., V.C., L.T., F.V., A.P., L.D.M.) and Laboratory of Vascular Biology and Genetics (F.A.), Department of Internal Medicine, Institute of Pathology (L.L., V.V.) and Institute of Neurosurgery (F.D., G.M.), Università Cattolica del Sacro Cuore, 00168 Rome, Italy; Section of Endocrinology (M.C.Z., M.R.A., E.C.d.U.), Department of Biochemical Sciences and Advanced Therapies, University of Ferrara, 44100 Ferrara, Italy; and Department of Internal Medicine (A.G.), University of Brescia, 25125 Brescia, Italy

Address all correspondence and requests for reprints to: Laura De Marinis, M.D., Section of Endocrinology, Department of Internal Medicine, Università Cattolica del Sacro Cuore, Via Cassia 901, 00168 Rome Italy. E-mail: laurademarinis{at}yahoo.it.

Context: Ki-67 is a marker of proliferation activity associated with invasiveness and prognosis in human tumors.

Objective: The aim of the study was to evaluate the Ki-67 index prognostic relevance in a group of acromegalic patients who underwent transsphenoidal surgery for a GH-secreting pituitary adenoma.

Material and Methods: We selected 68 consecutive acromegalic patients referred to our hospital during a 5-yr period. The Ki-67 index was determined by immunohistochemistry on tissue samples obtained from each adenoma after surgery. Those patients who were not completely cured after surgery began medical therapy with somatostatin analogs (SSAs). Periodical pituitary magnetic resonance imaging and hormonal evaluation were performed during the follow-up.

Results: Twenty-eight of 68 patients were cured after surgery (41%). Among the 40 patients treated with SSAs, 13 were considered uncontrolled. Pituitary magnetic resonance imaging showed residual/recurrent disease in 25 of 68 patients after 6 months. No correlation was found between Ki-67 index and age, tumor size, GH, or IGF-I plasma levels. Tumors described as having cavernous sinus invasion had a higher mean Ki-67 index as compared with noninvasive tumors (P < 0.01). The Ki-67 index was significantly lower in tumors in patients cured after surgery as compared with patients considered not cured (P < 0.01) and in tumors in patients controlled by SSA therapy as compared with patients considered as uncontrolled (P < 0.05).

Conclusion: The Ki-67 labeling index may predict clinical outcome in postsurgical management of acromegalic patients. We suggest routine Ki-67 evaluation in GH-secreting pituitary adenomas.