Comparison of loss of heterozygosity and microsatellite instability in adenocarcinomas of the distal esophagus and proximal stomach

Abstract

Adenocarcinoma of the gastroesophageal junction is rapidly rising in incidence. It has been proposed that these tumors be classified as three different types: distal esophageal (AEG I), cardia (AEG II), and subcardia (AEG III). Using comparative genomic hybridization (CGH) analysis, one recent study reported that the 14q chromosomal arm showed a significantly higher rate of deletion in esophageal than in cardia adenocarcinoma. Using a microsatellite analysis technique, we analyzed this area and regions in the vicinity of the APC, DCC, and p53 genes. Tumor and normal tissues were microdissected from 54 cases (27 AEG I and 27 AEG III). DNA was extracted and then amplified using seven fluorescent-labeled microsatellite markers, one pair each on 5q, 18q, and 17p and four on 14q. The results were analyzed for loss of heterozygosity (LOH) and microsatellite instability (MSI). LOH varied from 20% to 30% at each locus except for the 17p locus, where it was slightly above 50% in both groups. No significant differences in LOH or MSI were found between the esophageal and gastric tumors, including the 14q chromosomal arm. These results fail to confirm the finding that abnormalities on the 14q chromosomal arm distinguish between distal esophageal and proximal gastric tumors.

Differences and similarities of adenocarcinomas of the esophagus and esophagogastric junction

“…Investigation of loss of heterozygosity (LOH) is an important tool to detect potential losses of tumor suppressor genes which can characterize different kind of cancers. We and others tried to differentiate adenocarcinomas of the esophagus and gastric cardia according to their LOH pattern, but no significant differences could be identified between the two tumors [56,57]. While van Dekken et al found a significant difference at locus 14Q using comparative genomic hybridization [58], this could not be confirmed in other studies.…”

Loss of Heterozygosity and Immunohistochemistry of Adenocarcinomas of the Esophagus and Gastric Cardia

“…LOH analysis gives more specific information about changes near putative tumor suppressor genes, as compared with CGH. Only one study directly compared the occurrence of LOH in patients with adenocarcinomas of the distal esophagus and gastric cardia, but no differences were found (20). In the present study, we compared the prevalence of LOH in patients with distal esophageal adenocarcinoma and adenocarcinoma of the gastric cardia.…”

“…Several previous studies used comparative genomic hybridization (CGH) to quickly compare all of the chromosomal alleles and this did not show significant changes (36 -38). One study found significantly more loss for locus 14q in patients with esophageal adenocarcinoma using CGH, which could not be confirmed in a subsequent study by LOH analysis (20,23). LOH analysis gives more specific information about changes near putative tumor suppressor genes, as compared with CGH.…”

“…Several groups studied LOH in patients with distal esophageal adenocarcinoma, whereas studies in cardiac carcinoma are more limited (16 -19). Only one study directly compared the presence of LOH in patients with adenocarcinoma of either the esophagus or gastric cardia (20). For a better understanding of potentially different genetic changes in esophagogastric tumors, we studied several losses of heterozygosity in 62 carefully selected patients with adenocarcinoma of either the esophagus or gastric cardia.…”

Allelic loss of 14q32 in the pathogenesis of gastrointestinal and ampullary malignancies: mapping of the target region to a 17�cM interval

“…The gastric carcinoma revealed an irregular tubular pattern with mild to moderate cellular atypism and nuclear pleomorphism (magnification ·300) elements of ampullary (n=10) and gastric cancer (n=12) at the D14S267 locus (details in Table 1). The reason that D14S267 was chosen for screening comes from the initial deletion mapping of our study and its deletion in 20% of cardiac carcinoma in a prior report (Yanagi et al 2000). Apparent LOH at the locus was detected in one (10%) of the ampullary and two (16.7%) of the gastric cancers (16.7%) tested, respectively (Fig.…”