Multiple endocrine neoplasia: the Chilean experience

Abstract

Multiple endocrine neoplasia (MEN) types 1 and 2 are genetic diseases that are inherited as autosomal traits. The major clinical manifestations of multiple endocrine neoplasia type 1 include the so-called “3 P's”: parathyroid, pituitary, and pancreatic tumors, including gastroenteroneuroendocrine tumors. Genetic testing can be performed on patients and the potential carriers of the menin gene mutation, but the genotype-phenotype correlation in multiple endocrine neoplasia type 1 is less straightforward than multiple endocrine neoplasia type 2. Most likely, the main advantage of genetic testing in MEN1 is to exclude from further studies those who are negative for the genetic mutation if they belong to a family with a known history of MEN1. In Chile, we started with rearranged during transfection proto-oncogene genetic testing (MEN2) 15 years ago. We carried out a prophylactic total thyroidectomy to prevent medullary thyroid carcinoma in a three-year-old girl who presented with microscopic medullary thyroid carcinoma. More than 90% of the individuals who tested positive using a genetic test achieved a biochemical cure compared with only 27% of patients who receive a clinical diagnosis. Mutations are mainly located in exon 11; the most common is C634W, rather than C634R. Hypertensive crisis was the cause of death in three patients, and extensive distant metastases occurred in nine (including two patients with multiple endocrine neoplasia type 2B) of 14 patients. Earlier recognition of medullary thyroid carcinoma and the other features of the disease, especially pheochromocytoma, will improve the survival rate of patients with multiple endocrine neoplasia.

Downregulation of homeobox gene Barx2 increases gastric cancer proliferation and metastasis and predicts poor patient outcomes

“…Sellar et al found that Barx2 expression correlates with the expression of cadherin 6 and inhibits ovarian cancer cells’ ability to invade Matrigel and to adhere to collagen IV-coated plates [ 17 ]. Barx2 may mediate ras/raf dependent transcription of the calcitonin gene via a ras/raf responsive promoter element and loss of Barx2 -mediated differentiation may lead to loss of expression of the calcitonin marker, further resulting in MTC tumor progression [ 11 , 28 , 29 ]. In primary hepatocellular carcinoma, the expression of Barx2 had a negative correlation with markers of EMT, providing evidence that its low expression level in hepatocellular carcinoma was significantly correlated with tumor metastasis [ 16 ].…”

Primary hyperparathyroidism as first manifestation in multiple endocrine neoplasia type 2A: an international multicenter study

“…Data were drawn from the registry of each center. Some of the patients have been reported on previous occasions and updated data were obtained (17,18,19,20,21,22,23,24,25,26).…”

A differential diagnosis of inherited endocrine tumors and their tumor counterparts

“…Some of these cases have been followed for up to 10 years, and their calcitonin levels have remained undetectable, indicating that a “biochemical cure” was achieved (20,40,61). Preventive TTx has been successfully performed in MEN2 children from several Latin American countries, including Argentina, Chile, and Brazil (69-71). Preventive subtotal or total thymectomy should be performed in all MEN1 cases during PTx as recommended for HPT/MEN1 because the thymic carcinoid is a fast-evolving malignant tumor that is a frequent cause of death in MEN1 cases (8,10).…”