Residual nonfunctioning pituitary adenomas: prognostic value of MIB-1 labeling index for tumor progression

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In residual nonfunctioning pituitary adenomas, reliable prognostic parameters indicating probability of tumor progression are needed. The Ki 67 expression/MIB-1 labeling index (LI) is considered to be a promising candidate factor. The aim in the present study was to analyze the clinical usefulness of MIB-1 LI for prognosis of tumor progression.


The authors studied a cohort of 92 patients with nonfunctioning pituitary adenomas. Based on sequential postoperative MR images, patients were classified as tumor free (51 patients) or as harboring residual tumor (41 individuals). The residual tumor group was further subdivided in groups with stable residual tumors (14 patients) or progressive residual tumors (27 patients). The MIB-1 LI was assessed in tumor specimens obtained in all patients, and statistical comparisons of MIB-1 LI of the various subgroups were performed.


. The authors found no significant difference of MIB-1 LI in the residual tumor group compared with the tumor-free group. However, MIB-1 LI was significantly higher in the progressive residual tumor group, compared with the stable residual tumor group. Additionally, the time period to second surgery was significantly shorter in residual adenomas showing an MIB-1 LI > 3%.


The data indicate that MIB-1 LI in nonfunctioning pituitary adenomas is a clinically useful prognostic parameter indicating probability of progression of postoperative tumor remnants. The MIB-1 LI may be helpful in decisions of postoperative disease management (for example, frequency of radiographic intervals, planning for reoperation, radiotherapy, and/or radiosurgery).

Abbreviations used in this paper: LI = labeling index; NFPA = nonfunctioning pituitary adenoma; WHO = World Health Organization.

Article Information

Address correspondence to: Stefan Wolfsberger, M.D., Department of Neurosurgery, Medical University Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. email:

Please include this information when citing this paper: published online November 7, 2008; DOI: 10.3171/2008.4.17517.

© AANS, except where prohibited by US copyright law.



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    Chart showing definitions of patient subgroups.

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    Boxplot diagram comparing MIB-1 LI values between progressive and stable residual tumor groups. The MIB-1 LI was significantly higher in the progressive residual tumor group (p = 0.038), although this index showed a wide range. All patients with postoperative residual tumor and an MIB-1 LI ≥ 2% were part of the progressive residual tumor group. All patients in the stable residual tumor group had an MIB-1 LI < 2%.

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    Images of tumor obtained in a 56-year-old man in the progressive residual tumor group. A: Preoperative MR image revealing tumor. B: Photomicrograph showing tissue section obtained after transsphenoidal tumor removal and immunos-tained with MIB-1 antibody for diagnosis of null-cell adenoma, with an MIB-1 LI of 5.4%. Original magnification × 400. C: Postoperative MR image obtained at 6 months demonstrating uncertain residual tumor. D: Follow-up MR image obtained 1 year postoperatively with unequivocal residual tumor. E: Follow-up MR image obtained 2 years postoperatively. F: Follow-up MR image obtained 3 years postoperatively, demonstrating a continuously growing tumor remnant.

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    Images of tumor obtained in a 30-year-old man in the stable residual tumor group. A: Preoperative MR image revealing tumor. B: Photomicrograph showing tissue section obtained after transsphenoidal tumor removal and immunostained with MIB-1 antibody for diagnosis of null-cell adenoma, with an MIB-1 LI of 1.6%. Original magnification × 400. C: Postoperative MR image obtained at 6 months. D: Postoperative MR image obtained at 1 year. E: Postoperative MR image obtained at 3 years. F: Postoperative MR image obtained at 6 years. These follow-up images demonstrate residual tumor in the left superior cavernous sinus compartment; tumor was unchanged in size over 6 years.

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    Kaplan-Meier plot showing significantly shorter time to second operation in patients with residual adenomas and an MIB-1 LI > 3% (4.2 years in MIB-1 LI > 3% vs 9.4 years in MIB-1 LI ≤ 3%; p < 0.001, log-rank test). Patients with stable residual tumor were censored at last follow-up.


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