Loss Of Heterozygosity On Chromosome 9 In Esophageal Squamous Cell Carcinoma And Its Precursor Lesion

Objective: The inactivation of tumor suppressor genes(TSG) was one of the significant mechanisms of cell canceration. Possible tumor suppressor genes related to the development and progression of esophageal squamous cell carcinoma(ESCC) may exist at chromosome 9. The aim of this study was to investigate the gene variation and to evaluate possible tumor suppressor genes on chromosome 9 in the development and progression of ESCC, through detecting the loss of heterozygosity (LOH) in ESCC and its high-grade squamous dysplasia.Method: 45 cases of ESCC with high-grade squamous dysplasia and normal tissue were selected. LOH was detected in normal esophageal mucosa, high-grade squamous dysplasia and esophageal squamous cell carcinoma using microdissection, polymerase chain reaction, denaturing polyacrylamide gel electrophoresis and silver nitrate staining tecnology . The changes of LOH at seven microsatellite markers and the relationship between LOH rate and clinicopathologic parameters, enteron family history were analyzed. All analysis were carried out using SPSS11.0 software.Results: 1. In the informative cases, total frequency of LOH in high-grade squamous dysplasia was 16% and it was 26% in esophageal squamous cell carcinoma . In high grade squamous dysplasia, LOH was detected at marker D9S303 (31%), D9S171 (29%), D9S753 (29%), D9S162(15%), D9S242 (11%), D9S1748 (7%) and D9S43 (0%). In squamous cell carcinoma, LOH was detected as follows: D9S753 (43%),D9S303 (38%),D9S171 (36%),D9S162 (36%),D9S242 (17%),D9S1748 (17%) and D9S43 (0%). 2. The frequency of LOH in the seven microsatellite markers was found no associated with the sex, differentiation, and occurrence of lymph node metastasis (P > 0.05), but was showed significant difference with the enteron family history (χ2=4.86,P<0.05;χ2=5.11,P<0.05).Conclusions: 1. The progression from normal squamous epithelium to high- grade squamous dysplasia and subsequently to squamous cell carcinoma of the esophagus was associated with accumulation of genetic errors. 2. The p15 gene inactivation had a possible relationship with the development and progression of esophageal squamous cell carcinoma. 3. Possible tumor suppressor genes at or near D9S162 may be related to the progression of esophageal squamous cell carcinoma. 4. Possible tumor suppressor genes related to the development of esophageal squamous cell carcinoma may exist near chromosome 9p. 5. The frequency of LOH in cases with enteron family history was significantly higher than in cases with no enteron family history.