The Relationship Between Loss Of Heterozygosity Of FHIT Gene And Microsatellite Instability In Sporadic Colorectal Cancer

PurposeTo study the loss of heterozygosity (LOH) of FHIT gene and its relationship with microsatellite instability(MSI) in sporadic colorectal cancer, and to analysis their association with the clinical pathological characteristics of sporadic colorectal cancer.MethodsTo collect 63 cases fresh sporadic colorectal cancer tissues and matched normal tissues. LOH of FHIT gene were detected at two microsaterllite locis D3Sl300 and D3S1234, while MSI were detected at five microsaterllite locis BAT25, BAT26, D2S123, D5S346 and D17S250. Both detection methods were polymerase chain reaction single strand conformation polymorphism(PCR-SSCP) and silver staining. LOH of FHIT gene and MSI in sporadic colorectal cancer were analyzed in combination with the clinical data(age, sex, tumor location, tumor differentiation, Dukes stage and lymph node metastasis).Results1. LOH of FHIT gene:The number of informative samples was 59. The frequency of D3S1300 and D3S1234 LOH was 31.4% and 45.8% respectively.LOH of both locis were 12(22.0%).2. MSI:The number of informative samples was 52. Eight (15.4%) tumors in the study were MSI-H, 5 (9.6%) were low-frequency MSI (MSI-L) and 39 (75.0%) were microsatellite stable (MSS). The frequency of the five locis was BAT25(10.9%), BAT26(10.5%), D2S123(8.3%), D5S346(5.2%), D17S250(7.7%) respectively.3. One of the 8 MSI-H tumors exhibited non-information in LOH. Five of 7(71.4%) MSI-H tumors exhibited LOH of FHIT positive, Two of 7(28.6%) exhibited LOH of FHIT negative. Three of the 44 MSI-L/MSS tumors exhibited non-information in LOH. Six of 43(28.6%) MSI-L/MSS tumors exhibited LOH of FHIT positive, Thirty-five of 43(85.4%) exhibited LOH of FHIT negative. There was significant difference(p=0.004).4. There were significant correlation between MSI and tumor differentiation(p<0.05), while no significant correlation was found between MSI and other clinical pathological characteristics(age, sex, tumor location, Dukes stage and lymph node metastasis)(p>0.05). LOH of FHIT had a significant correlation with tumor differentiation and lymph node metastasis, while no significant correlation with other clinical pathological characteristics.Conclusion1. LOH of FHIT gene is associated with MSI in sporadic colorectal cancer, Functional defect of mismatch repair system may be a cause for LOH of FHIT gene.2. MSI and LOH of FHIT gene maybe played an important roles in the occurrence and development of sporadic colorectal cancer.