Large proportion of low frequency microsatellite-instability and loss of heterozygosity in pheochromocytoma and endocrine tumors detected with an extended marker panel.
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.
Kupka
Susan
S
Department of General, Visceral and Transplant Surgery, University Hospital of Tübingen, Waldhörnlestrasse 22, 72072 Tübingen, Germany. susan.kupka@med.uni-tuebingen.de
Haack
Birgit
B
Zdichavsky
Marty
M
Mlinar
Tanja
T
Kienzle
Christine
C
Bock
Thomas
T
Kandolf
Reinhard
R
Kroeber
Stefan-Martin
SM
Königsrainer
Alfred
A
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*