title: Large proportion of low frequency microsatellite-instability and loss of heterozygosity in pheochromocytoma and endocrine tumors detected with an extended marker panel.
abstract: OBJECTIVE
  Pheochromocytoma (PCC) is a usually benign tumor originated in the majority of patients from the adrenal medulla. Regarding sporadic forms of PCC, mechanisms of pathogenesis are largely unknown. Recently, microsatellite-instability (MSI) was discussed as genetic factor contributing to PCC development. Since microsatellite markers used for MSI detection have only been recommended for colorectal carcinoma (CRC), we established an extended marker set for MSI detection in PCC.
  
  
  METHODS
  Twenty-two PCC patients were analyzed applying 11 microsatellite markers. Our marker set comprised the reference panel for CRC and six additional markers, which have already been described to detect MSI in tumors other than CRC. Moreover, 23 endocrine tumors with gastrointestinal origin were examined in order to test the applicability of this marker panel.
  
  
  RESULTS
  Microsatellite-instability was detected in 41% of PCCs. Twenty-seven percent showed loss of heterozygosity (LOH) events affecting different chromosomal regions. Among the 23 patients with endocrine tumors, only three (one pancreatic endocrine tumor, one duodenal neuro-endocrine tumor, one hepatic metastasis of a primary tumor with unknown origin) demonstrated MSI.
  
  
  CONCLUSIONS
  The extended microsatellite panel is qualified to detect MSI in PCC. Nine percent of MSI-positive cases would have not been noticed by the use of the reference panel alone. PCCs are characterized by low frequency MSI pointing to failures in factors involved in DNA replication.
authors.affiliation: Department of General, Visceral and Transplant Surgery, University Hospital of Tübingen, Waldhörnlestrasse 22, 72072 Tübingen, Germany. susan.kupka@med.uni-tuebingen.de
authors.forename: Susan
authors.initials: S
authors.lastname: Kupka
authors.forename: Birgit
authors.initials: B
authors.lastname: Haack
authors.forename: Marty
authors.initials: M
authors.lastname: Zdichavsky
authors.forename: Tanja
authors.initials: T
authors.lastname: Mlinar
authors.forename: Christine
authors.initials: C
authors.lastname: Kienzle
authors.forename: Thomas
authors.initials: T
authors.lastname: Bock
authors.forename: Reinhard
authors.initials: R
authors.lastname: Kandolf
authors.forename: Stefan-Martin
authors.initials: SM
authors.lastname: Kroeber
authors.forename: Alfred
authors.initials: A
authors.lastname: Königsrainer
mesh_terms: D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics; D004701:Endocrine Gland Neoplasms / Q000235:genetics*; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D053842:Microsatellite Instability; D018895:Microsatellite Repeats; D008875:Middle Aged; D010673:Pheochromocytoma / Q000235:genetics*