Nonfunctioning pituitary adenomas: association of Ki-67 and HMGA-1 labeling indices with residual tumor growth

The postoperative biological behavior of nonfunctioning pituitary adenomas (NFPAs) is variable. Some residual NFPAs are stable long-term, others grow, and some recur despite complete removal. The usual histological markers of tumor aggressiveness are often similar between recurring, regrowing, and stable tumors, and therefore are not reliable as prognostic parameters. In this study, the clinical utility of proliferation indices (labeling index, Li) based on immunohistochemistry targeted at antigens Ki-67 and High-mobility group A1 (HMGA-1) for prediction of NFPA prognosis was investigated.

Fifty patients with NFPAs were investigated. In each patient, Ki-67 and HMGA-1 Li were evaluated. Based on postoperative magnetic resonance images, patients were classified as tumor-free (18 patients), or harboring a residual tumor (32 patients). The latter group was further subdivided into groups with stable tumor remnants (11 patients) or progressive tumor remnants (21 patients).

The median follow-up period was 8 years. No significant relationship between HMGA-1 Li and residual tumor growth was found. Growing residual tumors showed a trend towards higher Ki-67 Li compared with stable ones (p = 0.104). All tumor remnants with Ki-67 Li above 2.2% were growing. The relationship between residual tumor growth and Ki-67 Li exceeding the cutoff value of 2.2% was significant (p = 0.01 in univariate, p = 0.044 in multivariate analysis).

The prognostic significance of the HMGA-1 antigen was not confirmed. In contrast, the Ki-67 Li provides useful and valuable information for the postoperative management of NFPAs. In residual adenomas with a Ki-67 Li above 2.2%, regrowth should be expected, and these tumors may require shorter intervals of follow-up magnetic resonance imaging (MRI) and/or early adjuvant therapy. Future larger studies are needed to confirm the results of this study.