RT Journal Article SR Electronic T1 Replication Error-positive Samples Found in Pheochromocytomas JF In Vivo JO In Vivo FD International Institute of Anticancer Research SP 359 OP 365 VO 19 IS 2 A1 NIVES PECINA-SLAUS A1 TAMARA NIKUSEVA-MARTIC A1 KORALJKA GALL-TROSELJ A1 KRESIMIR RADIC A1 RENO HRASCAN YR 2005 UL http://iv.iiarjournals.org/content/19/2/359.abstract AB Background: Adenomatous polyposis coli, (APC) and E-cadherin (CDH1) tumor suppressor genes were investigated in human pheochromocytoma. Both genes are components of adherens junctions, but are also involved in wnt signalling in which one of the target molecules is c-myc protein. Materials and Methods: Fifteen sporadic pheochromocytomas were tested for gene instability by PCR/loss of heterozygosity. Detection of c-myc protein was performed using immunohistochemistry. Results: One sample with allelic imbalance of the APC gene and one with allelic imbalance of the CDH1 gene were found. Interestingly, another type of genomic instability was detected - replication error-positive samples (RER+). Four out of 13 heterozygous samples were RER-positive (30.8%). The instability is the result of impaired cellular mismatch repair. Immunohistochemistry showed increased levels of c-myc in comparison to normal adrenal tissue. Conclusion: Our results suggest that microsatellite genetic instabilities of the E-cadherin gene have a role in pheochromocytoma development and progression. Detected instability indicates that mismatch repair may be targeted in pheochromocytoma. Increased expression of c-myc protein as well as allelic imbalances of APC and CDH 1 genes suggest that the wnt signalling pathway may have a role in this malignancy.