Recently, correlations between corticotroph
tumor dedifferentiation and both
E-cadherin immunostaining and reduced
mRNA expression of the
E-cadherin gene (CDH1) have been demonstrated. The purpose of this study was to explore whether
tumor dedifferentiation correlated with
glucocorticoid resistance and whether the resistance was associated with both positively and negatively regulated genes.
Tumor material from 20 patients with verified
Cushing's disease or Nelson's syndrome operated on at Rikshospitalet, Oslo. Reverse transcription polymerase chain reaction analysis of genes such as
E-cadherin (CDH1),
proopiomelanocortin (
POMC),
glucocorticoid-induced leucine zipper (GILZ), and
thioredoxin-interacting
protein (TXNIP) was performed. The correlations between the expression of the GILZ, TXNIP, and
POMC genes in different stages of
corticotroph adenomas, the
E-cadherin mRNA expression and staining pattern, and the preoperative 24-h
cortisol excretion were examined. The GILZ and TXNIP expression levels were positively correlated to the CDH1 expression and were highest in microadenomas and in
tumors with a high membranous
E-cadherin reactivity. In contrast, the
POMC expression was not significantly different between the groups. This divergence between the genes that were positively and negatively regulated by
glucocorticoids could not be supported by other gene expression analyses. No correlations to urinary
cortisol were found. The expression of the
glucocorticoid-responsive genes
POMC, GILZ, and TXNIP in
corticotroph adenomas showed a remarkable variation. The pattern and variability of
glucocorticoid resistance in
corticotroph adenomas seem to correlate with a loss of the epithelial phenotype associated with corticotroph
tumor dedifferentiation.