Loss Of Multi-sites Allele Heterozygosity On Chromosome 9 In Esophageal Carcinoma

Objective:Esophageal Carcinoma and development occurs after a multistage,multi-step and multifactor process in which several genetic alterations accumulate,including oncogene activation,tumor-suppressor gene inactivation,mismatch repair genes deficiency as well as genetic instability at several microsatellite loci.The aim of this study was to investigate the gene variation and the dependability,at the same time to evaluate possible tumor suppressor genes on chromosome 9 in the development and progression of EC,through detecting the loss of heterozygosity(LOH)in EC and its high-grade squamous dysplasia.Method:36 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 six microsatellite markers and the relationship between LOH rate were analyzed.All analysis were carried out using SPSS13.0 software.Results:1.The patho-sarnple with high-grade squamous dysplasia are few.The patho-sample with atypical hyperplasia are less.2.In the informative cases,total frequency of LOH in high-grade squamous dysplasia was 17.2%and it was 24.9%in esophageal squamous cell carcinoma.In high grade squamous dysplasia,LOH was detected at marker D9S162(20.8%), D9S171(33.3%),D9S753(34.8%),D9S1748(4.2%),D9S242(14.3%)and D9S43(0%).In squamous cell carcinoma,LOH was detected as follows:D9S162(36.7%),D9S171(36%), D9S753(46.2%),D9S1748(13.8%)D9S242(21.2%)and D9S43(0%).3.The frequency of LOH was showed significant difference among the six microsatellite markers(X~2=17.26, P＜0.005;X~2=22.66,P＜0.005).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 chromosomal change.2.The situs of D9S171,D9S162,D9S242,D9S753 exist higher LOH and all exceed 20%.Possible tumor suppressor genes at or near D9S171,D9S162,D9S242,D9S753 may be related to the progression of esophageal squamous cell carcinoma.3. The LOH about Esophageal Carcinoma need profound investigation.4.The detection,diagnosis and treatment of esophago-atypical hyperplasia request discussion.