Warthin tumors do not have microsatellite instability and express normal DNA mismatch repair proteins.
BACKGROUND
Warthin tumors are controversial entities with a poorly understood etiology. Although some investigators have suggested a neoplastic origin, others have supported a developmental anomaly. A recent study described the absence of staining for hMLH1 and hMSH2 proteins in the epithelial component of Warthin tumors, suggesting that they arise secondary to defects in the DNA mismatch repair system.


OBJECTIVE
To determine if Warthin tumors exhibit evidence of DNA mismatch repair defects.


METHODS
Immunostains for hMLH1 and hMSH2 were performed using a standard approach. Microdissection of the epithelial component was followed by DNA extraction from the tissue fragments. Polymerase chain reaction and capillary electrophoresis analyses were performed for the following 5 National Cancer Institute-recommended microsatellites: D2s123, D5s346, D17s250, BAT25, and BAT26.


METHODS
Twelve patients with Warthin tumors were included.


RESULTS
The immunostains for hMLH1 and hMSH2 showed preserved expression in the nuclei of the epithelial component of all Warthin tumors. No microsatellite instability was detected, and no loss of heterozygosity was seen.


CONCLUSIONS
These results are not concordant with previously reported results showing loss of expression of the hMLH1 and hMSH2 DNA mismatch repair enzymes in the epithelial component of Warthin tumors. Furthermore, no microsatellite instability was detected in the 5 loci tested for each tumor in this series. These data demonstrate that Warthin tumors do not have evidence of DNA mismatch repair defects at the genomic or protein expression level.
Hunt
Jennifer L
JL
Head and Neck & Endocrine Pathology, Molecular Anatomic Pathology, Presbyterian Hospital A610.2, Pittsburgh, PA 15213, USA. huntjl@upmc.edu
D048868:Adaptor Proteins, Signal Transducing; D000235:Adenolymphoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D000368:Aged; D020137:Base Pair Mismatch / Q000235:genetics*; D002352:Carrier Proteins / Q000032:analysis; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000032:analysis; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics*; D009687:Nuclear Proteins / Q000032:analysis; D010307:Parotid Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004273:DNA, Neoplasm; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein