Loss of fragile histidine triad protein expression in inflammatory bowel disease

AIM： To investigate the expression of fragile histidine triad （FHIT） protein in 64 patients with ulcerative colitis （UC） and Crohn＇s disease （CD）, and its relation with clinicopathological data. METHODS： Rabbit-anti-FHIT antibody was used to detect FHIT protein expression in 64 formalin-fixed, paraffin-embedded tissue specimens of inflammatory bowel disease （IBD） by citrate-microwave-streptavidin （SP）-HRP immunohistochemical method. RESULTS： The positive FHIT protein expression was 22.79% ± 16.16%, 42.14% ± 16.82% in active and remittent phases of UC, 36.07% ± 19.23% in CD, and 57.05% ±8.86% in normal colon mucosa. Statistically significant differences in FHIT protein expression were observed between the active and remittent phases of UC, between the active phase of UC and normal colon mucosa, as well as between the remittent phase of UC and normal colon mucosa, and between CD and normal colon mucosa. CONCLUSION： Our results show that FHIT protein expression is completely absent or reduced in IBD, suggesting that the FHIT gene might be associated with the oncogenesis and progression of IBD, an early event from inflammatory conditions to carcinoma in IBD.

Expression of fragile histidine triad in primary hepatocellular carcinoma and its relation with cell proliferation and apoptosis

AIM: To evaluate the expression of fragile histidine triad (FHIT) gene protein, product of a candidate tumor suppressor, and to investigate the relationship between FHIT, cell apoptosis and proliferation, and pathological features of primary hepatocellular carcinoma (HCC). METHODS: Forty-seven HCC and ten normal liver specimens were collected during surgical operation between 2001 and 2003. FHIT and proliferating cell nuclear antigen (PCNA) expression were detected by immunohistochemistry, and apoptotic level was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay on the tissue sections. RESULTS: All normal liver tissues showed a strong expression of FHIT, whereas 28 of 47 (59.6%) carcinomas showed a significant loss or absence of FHIT expression (P= 0.001). The proportion of reduced FHIT expression in those carcinomas at stages Ⅲ-Ⅳ (70.6%) and in those with extrahepatic metastasis (86.7%) showed an increasing trend compared with those at stages HI (30.8%, P= 0.013) and those without metastasis (46.9%, P = 0.010) respectively. Apoptotic incidence in advanced TNM stage carcinoma and those with positive FHIT expression was higher than that in early stage carcinoma (P=0.030) and in those with negative FHIT expression (P=0.044) respectively. The proliferating potential of hepatocellular carcinoma was associated with FHIT expression (P= 0.016) and the aggressive feature (P = 0.019). Kaplan-Meier analysis demonstrated that the survival time of these 47 patients correlated with TNM stage, FHIT expression and metastasis. CONCLUSION: There is marked loss or absence of FHIT expression, as well as abnormal apoptosis-prdiferation balance in HCC. FHIT may play an important role in carcinogenesis and development of HCC.

MSI/LOH and extron expression of the FHIT gene in gastric carcinoma

We detected loss of heterozygosity(LOH)and microsatellite instabilities(MSI),as well as extron expression of the fragile histidine triad(FHIT)gene in gastric carcinoma(GC),in order to evaluate their association with clinicopathological processes in gastric carcinogenesis.LOH and MSI of the FHIT were detected by using PCR at 4 microsatellite loci:D3S 1300,D3S 4103,D3S 1481,D3S 1234 in cancer tissues from 50 patients with primary GC,with normal mucosa acting as matched controls.FHIT transcripts were detected by nested RT-PCR in 30 cases of GC and their products were sequenced.Results show that the average frequencies of LOH and MSI of the FHIT gene in GC were 32.4%and 26.4%,respectively.There was no correlation between LOH and MSI of the FHIT gene in GC and the histological characteristics of gastric carcinoma(Bormann’s or Lauren’s classification).LOH of the FHIT gene in GC was related to depth invasiveness,and its frequency in GC where serosa was penetrated was significantly higher than that in GC without serosa penetration(73.5%vs 37.5%,P<0.05).The frequency of MSI in GC without lymph node metastasis was significantly higher than that in GC with lymph node metastasis(66.7%vs 34.3%,P<0.05).Aberrant transcripts were found in 11/30 GC tissues.Sequencing analysis of the aberrant fragments found a RT-PCR product missing exons 5–7 in one case of GC,and another product missing exons 4–7.Four of 10(40.0%)cases of primary GC showed absent or decreased expression of the FHIT protein as compared to their matched normal tissues.The findings in this study suggest that LOH and MSI of FHIT gene may induce aberrant extron expression,which might play a role in gastric carcinogenesis.