Abstract
Background: 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.
Material and methods: 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%).
Results: 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.
Conclusions: 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.
Key words
non-functioning (inactive) pituitary adenoma - pituitary - tumor growth - digital
follow-up - Ki-67 - PCNA - p53 - IGF-I
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Correspondence
Prof. Dr. W. Saeger
Institute of Pathology of the Marienkrankenhaus
Alfredstraße 9
22087 Hamburg
Germany
Phone: +49/40/2546 27 01
Fax: +49/40/2546 27 30
Email: saeger.patho@marienkrankenhaus.org