The MEN 1 syndrome: the actual role of genetic testing on the timing and extent of surgery.

Abstract

Accepted: 21 January 2001 Published online: 27 February 2002 © Springer-Verlag 2002 MEN 2 is caused by activating mutations affecting at least 13 codons of the RET (rearranged during transfection) protooncogene. A genotype–phenotype correlation of clinical importance exists [4]. In contrast, the MEN 1 syndrome is caused by more than 200 presently known inactivating mutations of the tumor suppressor gene menin, none of which has been associated with a particular phenotype. Using clinical and genetic analyses, MEN 2 can be diagnosed in more than 95% of all cases, whereas a mutation rate of that frequency can only be found in typical MEN 1-families presenting with two or three organ manifestations (primary hyperparathyroidism, pituitary adenoma, or neuroendocrine tumor of the pancreas/duodenum). In oneorgan MEN 1 cases, the genetic detection rate is much lower (<30%). Hence, in contrast to MEN 2, no genotype-derived prophylactic surgical strategy is available in MEN 1 at present. Several articles in this issue of Langenbeck’s summarize the present knowledge regarding clinical and genetic diagnostic work-up in cases of suspected MEN 1 syndrome and give answers concerning the main surgical questions facing the endocrine surgeon: (1) Is the diagnosed organ lesion part of MEN 1-syndrome, and, if proven or highly suspected, (2) how radical should the surgery be? 1. Is the diagnosed organ lesion of the individual patient part of the MEN 1-syndrome? The reason for having to answer this question before surgical intervention comes from retrospective clinical and morphological studies that mostly showed a multifocal and earlier organ involvement compared to sporadic cases, [1,2], which is in accordance with other hereditary tumor syndromes. The clinical disease penetrance, i.e., the likeliness of gene carriers to develop clinical manifestations of the MEN 1 syndrome, is very high – approaching 90% at the age of 50 years. On the other hand, only 12% of MEN 1 patients exhibit two or more organ lesions at the time of first diagnosis. Only 10–40% of the cases with gastroenteropancreatic neuroendocrine tumors and less than 1% of cases with primary hyperparathyroidism are attributable to MEN 1. To distinguish MEN 1 from sporadic disease, clinical and genetic diagnostic procedures have to be developed to enable timely surgery that fits the underlying disease pathogenesis. The article by Karges et al. in this issue outlines practical guidelines regarding the indications for MEN 1 genetic testing in patients with suspected MEN 1 syndrome and clinical follow-up strategies in asymptomatic MEN 1 mutation carriers that have been developed recently within the German MEN 1 – Study Group [3]. Because of the fact that organ maniLangenbeck’s Arch Surg (2002) 386:545–546 DOI 10.1007/s00423-002-0280-3 E D I T O R I A L