6 research outputs found
Malignant Fibrous Histiocytoma, Aggressive Fibromatosis and Benign Fibrous Tumors Express mRNA for the Metalloproteinase Inducer EMMPRIN and the Metalloproteinases MMP-2 and MT1-MMP
Purpose: Extracellular matrix metalloproteinase inducer (EMMPRIN) has been shown to stimulate fibroblasts to production
of matrix metalloproteinases (MMPs). MMPs comprise a family of proteolytic enzymes implicated in the degradation
of extracellular matrix which has been proposed to be one of the essential steps in tumor invasion and metastases. In the
present study we investigated the expression and location of mRNAs for EMMPRIN, matrix metalloproteinase-2 (MMP-2),
and membrane-type 1 matrix metalloproteinase (MT1-MMP) in mesenchymal tumors with different tendencies to recur or
metastasize
Functional and diagnostic aspects on adrenocortical adenoma
Adrenocortical tumours are frequently detected due to increased use of
imaging techniques like computed tomography, magnetic resonance imaging
or ultrasound. The majority of the patients have tumours that do not have
any overproduction of hormone. The functional adrenocortical adenomas are
characterized by overproduction of one of the corticosteroids
aldosterone, cortisol or androgen. The most common are aldosteronoma and
cortisol producing adenoma. It is not possible to differentiate
aldosterone and cortisol producing adenoma by histopathological
examination. Thus, the clinical data and determination of steroid
hormones in blood and urine form the basis to conclude if the extirpated
tumour has been functional.
The aim of the study was to increase our knowledge of the pathophysiology
of adrenocortical lesions.
Paper I. An in situ-hybridisation method was developed to use
radioactively labelled oligonucleotide probes on paraffin embedded tissue
material to demonstrate the gene expression of the steroid synthesizing
enzymes and thereby identify the steroid production of adrenocortical
adenoma. In vitro release of aldosterone and cortisol from thin slices
was compared to the mRNA expression of CYP11B2, CYP11B1 and CYP17, which
are coding for the specific enzymes needed for the aldosterone and
cortisol synthesis. The results indicate that CYP11B2 expression reflects
aldosterone production in the tumour, while CYP17 and CYP11B1 reflects
cortisol production.
Paper II. The most common forms of primary aldosteronism are unilateral
adenoma and bilateral hyperplasia. To attain an optimal treatment there
is a demand for thorough functional characterization since adrenalectomy
often cures patients with adenoma while patients with hyperplasia are
treated medically. To improve the subclassification of primary
aldosteronism 27 operated patients were evaluated. CYP11B2 expression was
found in an adenoma from 22 patients. Fourteen of these had additional
CYP11B2 expression in zona glomerulosa. All these 22 patients were cured
from hyperaldosteronism. Three patients, who were not cured, had probably
bilateral disease. Two adrenal adenoma had no CYP11B2 expression, but the
patients were cured.
These results contribute to entirely new possibilities to,
postoperatively, determine a correct subclassification of patients with
primary aldosteronism.
Paper III. The value of adrenal scintigraphy in lateralisation of
aldosterone producing adrenocortical adenoma was investigated in 33
patients, who were evaluated according to cure and compared to the
scintigraphic pattern. Twenty-seven patients had scintigraphic images
showing a unilateral uptake or a bilateral asymmetric uptake indicating
unilateral aldosterone overproduction. Twenty-two of these patients were
cured, 3 patients were improved, and 2 patients were not cured. Six
patients had no uptake at scintigraphy. Adrenal scintigraphy at primary
aldosteronism may be a useful complement at the preoperative
lateralisation.
Paper IV. The majority of adrenocortical incidentaloma are
non-hyperfunctioning adrenal adenoma. Some of them may have autonomous
cortisol production not fully restrained by the
hypothalamus-pituitary-adrenal-axis. The median ratio of CYP17 to CYP11B1
expression for tumours from patients with Cushing´s syndrome was
significantly higher than the median ratio for the non-hyperfunctioning
tumours. In patients with subclinical Cushing´s syndrome the tumours have
a similar high ratio indicating that these patients may be identified
with this method