It is estimated that the risk of neoplasia in Barrett esophagus, through the intermediate step of dysplastic transformation of the columnar epithelium, is 125-fold higher than in general population. But scarce data are available on genetic alterations occurring in metaplasia-dysplasia-adenocarcinoma sequence of Barrett esophagus. A research group in China investigated the microsatellite alterations on D2S123, D3S1616, D3S1300, D5S346, D17S787, D18S58 and BATRII loci, using the technique of dilution polymerase chain reaction (PCR).
This will be published on 7 July 2008, in the World Journal of Gastroenterology. Using an approach that tissue in slice was dissected under microscopic guidance. The technique ensures enrichment and purity of the tissues to be studied and guarantees the specificity of the molecular event encountered. Meamwhile, they diluted DNA of metaplasia, dysplasia, adenocarcinoma and normal esophageal squamous epithelium at the same patient, and attempted to proceed PCR, that is called dilution PCR. Dilution PCR, the more sensitive strategy for analyzing microsatellite changes was developed, reasoning that if a rare cell in a population harbored microsatellite alterations, the new microsatellite alleles would not be detectable amid the large background of normal alleles. The results indicate that the MSI and LOH may be early genetic events during esophageal carcinogenesis, that additional genetic alterations on D3S1616, D5S346, D2S123, D3S1300 and D18S58 loci probably play roles in progression. The results also indicate that microsatellite markers D3S1616, D5S346, D2S123, D3S1300 and D18S58 loci may be useful as predictive markers in the early detection of esophageal adenocarcinoma.
Interestingly, microsatellite alterations have been detected in all eight patients having the "sequence" with a representative DNA dilution. Similarly, microsatellite alterations have been detected both in metaplasia and dysplasia adjacent to adenocarcinoma at above 7 microsatellite loci. The more the dilution of DNA, the higher the rate of microsatellite alterations it usually has D3S1616, D5S346, D2S123, D3S1300, and D18S58 loci depending on development of the metaplasia-dysplasia-adenocarcinoma sequence. These results clearly reveal that there were extensive microsatellite alterations in D3S1616, D5S346, D2S123, D3S1300 and D18S58 loci in the metaplasia-dysplasia-adenocarcinoma sequence of Barrett esophagus, even in the histopathologically normal esophageal squamous epithelium. The observations of shared molecular abnormalities in metaplasia, dysplasia and adenocarcinoma suggested a process of colonal expansion under the proposed histological pathway of tumor development, and these results may be partly interpreted by the idea that only the partial cells gained molecular alterations in the cell populations of similar circumstance.
Tumor development in Barrett esophagus is proposed to occur via a multi-step pathway, recognized histopathologically as a metaplasia-dysplasia-adenocarcinoma sequence. Certain molecular abnormalities under the form of proto-oncogene alterations, LOH of putative tumor suppressor genes and mutations of tumor suppressor genes are thought to represent the genetic background of metaplastic and dysplastic changes. In recent years, frequent or infrequent microsatellite instability at multiple microsatellite loci corresponding to diverse tumor suppressor genes have been demonstrated in colorectal, small bowel and gastric adenocarcinoma . The results suggest that the development of esophageal adenocarcinoma is associated with microsatellite alterations, including MSI and LOH, and that these alterations occur in recognized precursor lesion.