E. Edstrom et al., Expression analysis of RET and the GDNF/GFRa-1 and NTN/GFRa-2 ligand complexes in pheochromocytomas and paragangliomas, INT J MOL M, 6(4), 2000, pp. 469-474
Pheochromocytoma and its extra-adrenal counterpart paraganglioma are rare c
atecholamine producing tumors which usually occur sporadically but may also
be a part of neuroendocrine tumor syndromes such as multiple endocrine neo
plasia type 2A (MEN 2A). Activating mutations of the RET proto-oncogene whi
ch is the underlying cause of MEN 2A, is also seen in approximately 10% of
sporadic pheochromocytomas. Glial cell line derived neurotrophic factor (GD
NF) and neurturin (NTN) have been shown to function as independent ligands
to RET, binding in a complex with the membrane-bound receptors GFR alpha-1
and GFR alpha-2 respectively. Here we have investigated the mRNA expression
of RET and its ligand complexes, GDNF/GFR alpha-1 and NTN/GFR alpha-2, in
a panel of pheochromocytomas and paragangliomas using mRNA in situ hybridiz
ation. RET expression was evident in normal adrenal medulla, and in 13/15 p
heochromocytomas, including 5/5 MEN 2A associated tumors, but only in 1/10
paragangliomas. The frequent expression of RET in the pheochromocytomas sug
gest that this gene might be involved in the tumorigenesis. However, no exp
ression of GDNF/GFR alpha-1 or NTN/GFRa-2 could be detected in any of the 2
5 tumors analyzed, suggesting that these ligand complexes are not important
in the development of pheochromocytoma or paraganglioma.