BACKGROUND: Malignant
neoplasia of the adrenal cortex is usually associated with very poor prognosis. When adrenocortical
neoplasms are diagnosed in the early stages, distinction between
carcinoma and
adenoma can be very difficult to accomplish, since there is yet no reliable marker to predict
tumor recurrence or dissemination.
GATA transcription factors play an essential role in the developmental control of cell fate, cell proliferation and differentiation, organ morphogenesis, and tissue-specific gene expression. Normal mouse adrenal cortex expresses GATA-6 while its malignant counterpart only expresses GATA-4. The goal of the present study was to assess whether this reciprocal change in the expression of
GATA factors might be relevant for predicting the prognosis of human adrenocortical
neoplasms. Since human adrenal cortices express
luteinizing hormone (
LH/hCG) receptor and the
gonadotropins are known to up-regulate GATA-4 in gonadal tumor cell lines, we also studied the expression of
LH/hCG receptor. METHODS: We conducted a study on 13 non-metastasizing (NM) and 10 metastasizing/recurrent (MR)
tumors obtained from a group of twenty-two adult and pediatric patients. The expression of GATA-4, GATA-6, and
LH/hCG receptor (LHR) in normal and tumoral human adrenal cortices was analysed using
reverse transcriptase-polymerase chain reaction (RT-PCR) complemented by dot blot hybridization. RESULTS:
Messenger RNA for GATA-6 was detected in normal adrenal tissue, as well as in the totality of NM and MR
tumors. GATA-4, by its turn, was detected in normal adrenal tissue, in 11 out of 13 NM
tumors, and in 9 of the 10 MR
tumors, with larger amounts of
mRNA found among those presenting aggressive clinical behavior. Transcripts for
LH receptor were observed both in normal tissue and
neoplasms. A more intense LHR transcript accumulation was observed on those
tumors with better clinical outcome. CONCLUSION: Our data suggest that the expression of GATA-6 in human adrenal cortex is not affected by
tumorigenesis. GATA-4 expression is more abundant in MR
tumors, while NM
tumors express more intensely LHR. Further studies with larger cohorts are needed to test whether relative expression levels of LHR or GATA-4 might be used as prognosis predictors.