Assessment of the role of transcript for GATA-4 as a marker of unfavorable outcome in human adrenocortical neoplasms

被引：20

作者：

Barbosa A.S. ^{[1
]}

Giacaglia L.R. ^{[1
]}

Martin R.M. ^{[1
,2
]}

Mendonca B.B. ^{[1
,2
]}

Lin C.J. ^{[1
]}

机构：

[1] Lab. de Hormonios Genet. Molecular, Hospital das Clínicas, Universidade de São Paulo, São Paulo

[2] Divisão de Endocrinologia, Departamento de Clinica Medica, Universidade de São Paulo, São Paulo

来源：

BMC Endocrine Disorders | / 4卷 / 1期

关键词：

Luteinizing Hormone Receptor; Adrenocortical Neoplasm; Leydig Cell Tumor; Inducible cAMP Early Repressor; Endodermal Sinus Tumor;

D O I：

10.1186/1472-6823-4-3

中图分类号：

学科分类号：

摘要：

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. © 2004 Barbosa et al; licensee BioMed Central Ltd.

引用

页数：11

共 43 条

[1]

Flack M.R., Chrousos G.P., Neoplasms of the adrenal cortex, Cancer Medicine, pp. 1567-1570, (1996)

[2]

Latronico A.C., Chrousos G.P., Extensive personal experience: Adrenocortical tumors, J. Clin. Endocrinol. Metab., 82, pp. 1317-1324, (1997)

[3]

Wajchenberg B.L., Albergaria Pereira M.A., Medonca B.B., Latronico A.C., Campos Carneiro P., Alves V.A., Zerbini M.C., Liberman B., Carlos Gomes G., Kirschner M.A., Adrenocortical carcinoma: Clinical and laboratory observations, Cancer, 88, pp. 711-736, (2000)

[4]

Weiss L.M., Comparative histologic study of 43 metastasizing and nonmetastasizing adrenocortical tumors, Am. J. Surg. Pathol., 8, pp. 163-169, (1984)

[5]

Aubert S., Wacrenier A., Leroy X., Devos P., Carnaille B., Proye C., Wemeau J.L., Lecomte-Houcke M., Leteurtre E., Weiss system revisited: A clinicopathologic and immunohistochemical study of 49 adrenocortical tumors, Am. J. Surg. Pathol., 26, pp. 1612-1619, (2002)

[6]

Gicquel C., Bertagna X., Gaston V., Coste J., Louvel A., Baudin E., Bertherat J., Chapuis Y., Duclos J.M., Schlumberger M., Plouin P.F., Luton J.P., Le Bouc Y., Molecular markers and long-term recurrences in a large cohort of patients with sporadic adrenocortical tumors, Cancer Res., 61, pp. 6762-6767, (2001)

[7]

Weiss L.M., Medeiros L.J., Vickery Jr. A.L., Pathologic features of prognostic significance in adrenocortical carcinoma, Am. J. Surg. Pathol., 13, pp. 202-206, (1989)

[8]

Haak H.R., Cornelisse C.J., Hermans J., Cobben L., Fleuren G.J., Nuclear DNA content and morphological characteristics in the prognosis of adrenocortical carcinoma, Br. J. Cancer, 68, pp. 151-155, (1993)

[9]

Mendonca B.B., Lucon A.M., Menezes C.A., Saldanha L.B., Latronico A.C., Zerbini C., Madureira G., Domenice S., Albergaria M.A., Camargo M.H., Et al., Clinical, hormonal and pathological findings in a comparative study of adrenocortical neoplasms in childhood and adulthood, J. Urol., 154, pp. 2004-2009, (1995)

[10]

Sredni S.T., Zerbini M.C., Recommendations for reporting of tumors of the adrenal cortex and medulla, Mod. Pathol., 12, pp. 835-839, (1999)

← 1 2 3 4 5 →