Replication error-positive samples found in pheochromocytomas.
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.


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.


CONCLUSIONS
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.
Pecina-Slaus
Nives
N
Department of Biology, School of Medicine, University of Zagreb, Salata 3, HR-10000 Zagreb, Croatia. nina@mef.hr
Nikuseva-Martic
Tamara
T
Gall-Troselj
Koraljka
K
Radic
Kresimir
K
Hrascan
Reno
R
D000310:Adrenal Gland Neoplasms / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D015820:Cadherins / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D017491:Genes, APC; D042822:Genomic Instability; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D010673:Pheochromocytoma / Q000235:genetics* / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis
D015820:Cadherins; D004273:DNA, Neoplasm; D016271:Proto-Oncogene Proteins c-myc