Clinical tumor growth and comparison with proliferation markers in non-functioning (inactive) pituitary adenomas

As the development of clinically silent pituitary adenomas is not yet fully understood, the radiologically measured growth of inactive pituitary adenomas should be compared with adenoma classification and immunostainings for proliferation markers.

In 32 patients with non-functioning adenomas (NFA) from 45 operations with retrospectively available preoperative series of magnetic resonance imaging (MRI) we measured the largest growing diameter (LGD) in mm/ year. The adenomas were immunostained for Ki-67 (MiB-1), PCNA, p53 protein, IGF- and PTH-related protein. The positive nuclei for MiB-1, PCNA, and p53 protein were counted and their labelling indices (LI) were calculated. The clinical measurements were compared with these data and were statistically analysed (Spearman test, Whitney-U-test). The growth rate per year was available in 28 cases. We chosed three grades of LGD: less than 1.5 mm in diameter in 9 patients (32%), between 1.5 and 3.0 mm in 11 patients (39%) and more than 3.0 mm in 8 patients (29%).

MiB-1 positive nuclei were found in 42% of adenomas, PCNA positive nuclei in 58% and p53 positive nuclei in 16%. IGF 1 was immuno-stained in 84% of adenomas. The mean LI for MiB-1 was 0.12 in adenomas growing less than 1.5 mm and 0.34 in adenomas growing more than 1.5 mm per year. For non-invasive adenomas, the MiB-1 LI was 0.03, for invasive adenomas it was 0.126 and for strongly invasive adenomas 0.212. The MiB-1 LI was lower in null cell adenomas than in FSH/LH adenomas. All these data for MiB-1 showed no statistically significant differences (p<0.05). PCNA LI in adenomas growing less than 1.5 mm per year was 0.51 in contrast to LI of 1.12 for those growing more than 1.5 mm. In non-invasive adenomas the PCNA LI was 0.796, in invasive adenomas 0.655 and in diffuse strongly invasive ones 1.011. Null cell adenomas had a lower PCNA LI than FSH/LH cell adenomas.

Statistically significant differences were measured for the growth rate und the PCNA expression. P53 was immunostained in invasive adenomas only. There were no correlations to the clinical growth rate, but p53 expression correlated significantly to numbers of MiB-1 positive nuclei and PCNA positive nuclei. IGF-I expression was found to correlate inversely with age of patients. We recommend the use of PCNA if correlations to progression of tumor growth are wanted.