Abstract
BackgroundMalignant 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.MethodsWe 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.ResultsMessenger 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.ConclusionOur 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.
Highlights
Malignant neoplasia of the adrenal cortex is usually associated with very poor prognosis
In order to enhance the detection sensitivity and to perform quantitative analysis of GATA-6 and GATA-4 accumulation, amplification products from a second reverse transcriptase-polymerase chain reaction (RT-PCR) were vacuum-transferred to a membrane and subjected to dot-blot hybridization
Both GATA-6 and GATA-4 transcripts were detectable in normal adrenal and in NCI-H295A cells, with GATA-6 being more abundant than GATA-4 (Figure 1)
Summary
Malignant neoplasia of the adrenal cortex is usually associated with very poor prognosis. 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. Malignant neoplasia of the adrenal cortex is a rare pathological condition accounting for 0.05% – 0.2% of all cancers [1] These tumors are usually associated with unfavorable prognosis. The evaluation of combined histologic features and establishment of specific scores, as proposed by Weiss [4], poses, some technical difficulties, even for skilled pathologists. This is true for criteria such as nuclear grade, venous or sinusoid invasion, and diffuse architecture [5]. Weiss classification tends to be inaccurate for tumoral behavior prediction in children [9,10]
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