Microsatellite instability and hMLH1/hMSH2 expression in Barrett esophagus-associated adenocarcinoma.
BACKGROUND
Microsatellite instability (MSI) has been documented in malignancies associated with hereditary nonpolyposis colon carcinoma and in sporadic malignancies of the colon, stomach, and endometrium. In these malignancies, MSI is associated with defects in the DNA mismatch repair enzymes hMSH2 and hMLH1. Defects in these enzymes result in a phenotype characterized by instability of multiple microsatellite repeat sequences throughout the genome. This study sought to determine the prevalence of MSI in 80 primary Barrett esophagus-associated adenocarcinomas (BEAd) and to examine the relation of MSI with the clinical and pathologic features of the tumors.


METHODS
Eighty BEAd were evaluated for the presence of MSI by using the microsatellite markers BAT25, BAT26, D10S219, D10S541, and D10S551. These tumors also were evaluated for immunohistochemical expression of hMSH2 and hMLH1.


RESULTS
High levels of MSI were not found in any of the tumors examined. Furthermore, immunohistochemical expression of hMSH2 and hMLH1 was retained in all cases evaluated. Evidence of low level MSI was found in 16% of tumors. In none of these tumors, however, was MSI present in more than two of five loci. The presence of MSI did not correlate with patient age, tumor stage, degree of differentiation, or with patient survival.


CONCLUSIONS
High level MSI and loss of hMLH1/hMSH2 expression is uncommon in BEAd. A subset of BEAd demonstrate low level MSI. The presence of low level MSI was not associated with the clinicopathologic features of the tumors examined.
Kulke
M H
MH
Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA. mhkulke@bics.bwh.harvard.edu
Thakore
K S
KS
Thomas
G
G
Wang
H
H
Loda
M
M
Eng
C
C
Odze
R D
RD
D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D001471:Barrett Esophagus / Q000150:complications / Q000235:genetics*; D002352:Carrier Proteins; D015331:Cohort Studies; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000378:metabolism; D009687:Nuclear Proteins; D015995:Prevalence; D011379:Prognosis; D016019:Survival Analysis
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1