Fragile Histidine Triad Protein Expression Research Articles

Effects of FHIT gene on proliferation and apoptosis of osteosarcoma cells.

Regulatory effects of fragile histidine triad (FHIT) gene on proliferation and apoptosis of osteosarcoma cells were studied. The hFOB1.19 and Saos2 cells were routinely cultured, pcDNA3.1-FHIT overexpression vectors carrying FHIT gene fragments and blank pcDNA3.1 vectors were transfected into Saos2 cells, respectively, and the cells were divided into hFOB, Saos2, transfection and no-load transfection groups. After transfection for 48 h, the cells were collected and analyzed. The expression of FHIT messenger ribonucleic acid (mRNA) was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The expression of FHIT protein was detected by western blot analysis. Cell Counting Kit 8 (CCK8) was used to detect cell proliferation, and flow cytometry was used to detect apoptosis. The expression of FHIT mRNA was significantly decreased in Saos2 group compared with that in hFOB group, and the difference was statistically significant (P<0.05). The expression of FHIT mRNA was significantly increased in transfection group compared with that in Saos2 group, and the difference was statistically significant (P<0.05). The expression of FHIT protein was obviously decreased in Saos2 group compared with that in hFOB group, and there was a statistically significant difference (P<0.05). The expression of FHIT protein was obviously increased in transfection group compared with that in Saos2 group, and the difference was statistically significant (P<0.05). Compared with that in the hFOB group, the cell proliferation rate was remarkably increased in Saos2 group, while the apoptosis rate was remarkably decreased, showing statistically significant differences (P<0.05). Compared with those in Saos2 group, the cell proliferation rate was significantly decreased in transfection group, while the apoptosis rate was significantly increased, and the differences were statistically significant (P<0.05). In conclusion, FHIT gene regulates the proliferation and apoptosis of Saos2 osteosarcoma cells, inhibits the proliferation and promotes apoptosis of Saos2 osteosarcoma cells.

The Clinical Relevance of Fragile Histidine Triad Protein (FHIT) in Patients with Bladder Cancer.

BackgroundThe present study aimed to investigate the clinical relevance of fragile histidine triad protein (FHIT) in patients with bladder cancer (BC).Material/MethodsThree independent BC microarray studies were collected and reanalyzed. The expression of FHIT was evaluated between BC samples and normal bladder tissues. The correlation between the expression of FHIT and clinicopathological features was analyzed using the chi-square test. Log-rank based survival analysis was conducted to detect the survival significance of FHIT in patients with BC. Gene set enrichment analysis (GSEA) was performed to identify the mechanisms.ResultsFHIT was significantly downregulated in BC cells (p=0.0044). BC patients in the FHIT high expression group had better clinical characteristics (including invasiveness, tumor grade, disease progression, and T staging) than those in the FHIT low expression group (p<0.0001, p<0.0001, p=0.031, p<0.0001, and p=0.056, respectively). Patients in the FHIT high expression group had better cancer-specific survival (p<0.0001) and overall survival (p=0.0008) than those in the FHIT low expression. GSEA results indicated that BC samples in the FHIT low expression group were enriched in interferon alpha response, apoptosis, androgen response, interferon gamma response, heme metabolism, and transforming growth factor (TGF) beta signaling.ConclusionsFHIT predicts better clinical relevance for patients with BC, which may be a promising therapeutic target.

Interaction between abnormal expression of fragile histidine triad and methyl-CpG-binding protein 2 on cervical cancerization

Objective: To explore the relationship between abnormal expression of fragile histidine triad (FHIT) gene and methyl-CpG-binding protein 2 (MeCP2) as well as their interaction on cervical cancerization. Methods: A total of 73 patients with cervical squamous cell carcinoma (SCC), 113 patients with cervical intraepithelial neoplasia (CIN Ⅰ, n=45; CINⅡ/Ⅲ, n=68) and 60 women with normal cervix (NC) were included in the study. Real time PCR and Western blot were performed to detect the expression levels of mRNA and protein about FHIT and MeCP2, respectively. The methylation status of FHIT gene CpG island was tested by methylation-specifc PCR (MSP). Kruskal-Wallis H test, χ(2) test, trend χ(2) test and Spearman correlation analysis were conducted with software SPSS 20.0. The interaction was evaluated by generalized multifactor dimensionality reduction (GMDR) model. Results: With the deterioration of cervical lesion, the methylation rates of FHIT gene CpG island (χ(2)=18.64, P<0.001; trend χ(2)=18.08, P<0.001) increased gradually, while the expression levels of FHIT mRNA (H=27.32, P<0.001; trend χ(2)=12.65, P<0.001) and protein (H=47.10, P<0.001; trend χ(2)=29.79, P<0.001) decreased gradually. There was a negative correlation between the methylation rates of FHIT gene CpG island and the expression level of FHIT protein (r=-0.226, P<0.001). The levels of MeCP2 mRNA (H=26.19, P<0.001; trend χ(2)=11.81, P=0.001) and protein (H=69.02, P<0.001; trend χ(2)=47.44, P<0.001) increased gradually with the aggravation of cervical lesions. There was a positive correlation between the expression level of MeCP2 protein and the FHIT mRNA Ct ratio (r=0.254, P<0.001). Expression of proteins were negatively correlated between MeCP2 and FHIT (r=-0.213, P=0.001). The results analyzed by GMDR model showed that there were interactions among high MeCP2 protein expression, the CpG island methylation of FHIT and mRNA and protein expression in CINⅡ/Ⅲ group, and among high MeCP2 mRNA and protein expression, the CpG island methylation of FHIT and low mRNA and protein expression in SCC group. Conclusion: High expression of MeCP2 mRNA and protein, the CpG island methylation and low mRNA and protein expression of FHIT could increase the risk of cervical carcinogenesis, and there might be a synergistic effect on cervical carcinogenesis.

Folate deficiency and aberrant DNA methylation and expression of FHIT gene were associated with cervical pathogenesis.

Aberrant DNA methylation is a recognized feature in various types of human cancer, and folate has a vital role in the epigenetics of mammalian cells by supplying methyl groups for DNA methylation reactions. Fragile histidine triad (FHIT) is a tumor suppressor gene that is frequently silenced in cervical cancer (CC) and preneoplastic lesions. Promoter hypermethylation was previously observed in CC, and its epigenetic silencing has been observed at mRNA or protein levels. Changes in folate intake to modulate DNA methylation may be a mechanistic link to cancer, but this remains to be elucidated. The aim of the present study was to evaluate the influences of folate on FHIT gene methylation and expression in the progression of cervical cancerization. In the present study, red blood cell (RBC) folate levels, FHIT gene methylation status, and mRNA and protein expression levels were detected in 254 women, including normal cervix (NC, n=80), cervical intraepithelial neoplasm grade 1 (CIN1, n=55; CIN2/3, n=55) and cervical squamous cell carcinoma (SCC, n=64) samples. The methylation status of FHIT gene and its mRNA and protein expression levels were measured in CaSki (HPV16 positive) and C33A (HPV16 negative) CC cells treated with different concentrations of folate. The results indicated that FHIT gene methylation rate increased with the severity of cervix lesions, however, RBC folate levels, FHIT mRNA and protein expression levels were reduced. The proliferation inhibition rate, apoptosis rate, and FHIT protein and mRNA expression levels increased along with rising concentrations of folate, whereas the degree of FHIT gene methylation gradually weakened in CaSki or C33A cell lines. The present findings indicated that folate deficiency, FHIT gene promoter hypermethylation and reduced expression were significantly associated with cervical carcinogenesis. The results indicated that folate was able to enhance apoptosis and inhibit the cervical cell proliferation while regulating FHIT gene methylation and expression. Adequate intake of folate to maintain normal DNA methylation status is an effective way for cervical lesions prevention, and demethylation treatment may offer a new strategy for therapy of CC.

Fragile histidine triad protein expression in colorectal adenoma and carcinoma

Fragile histidine triad protein expression in colorectal adenoma and carcinoma

Association of FHIT expression and FHIT gene hypermethylation with liver cancer risk: a PRISMA-compliant meta-analysis.

BackgroundThere have been suggestions that fragile histidine triad protein (FHIT) expression and FHIT gene hypermethylation were crucial to the pathogenesis of liver cancer. However, the conclusions remained unclear because of small sample size, disease subtype, and different detection techniques. Therefore, we performed a meta-analysis to estimate the associations of FHIT expression and FHIT gene hypermethylation with liver cancer pathogenesis.MethodsStudies that were published in electronic databases, such as PubMed, Web of Knowledge, China National Knowledge Infrastructure (CNKI), VIP, and WanFang, were retrieved and selected for the meta-analysis. Relative risk (RR) and 95% confidence interval (CI) were calculated to determine the correlations of FHIT expression and FHIT gene hyper-methylation with liver cancer pathogenesis with Stata 12.0 software.ResultsA total of 17 papers that evaluated the associations of FHIT expression (14 articles) and FHIT gene methylation (3 articles) with liver cancer pathogenesis were included in this meta-analysis. In the overall analysis, the pooled relative risk was 1.93 (95% CI =1.72–2.17), which indicated a significant association between FHIT low expression and liver cancer risk. According to the results of clinical information, there were significant associations of FHIT expression with TNM-stage (RR =2.13, 95% CI =1.72–2.64), tumor size (RR =1.67, 95% CI =1.36–2.05), and merger of cirrhosis (RR =1.34, 95% CI =1.06–1.69) of liver cancer in the Chinese population. In addition, the FHIT gene hypermethylation was significantly associated with the risk of liver cancer (RR =1.45, 95% CI =1.08–1.93).ConclusionThe FHIT expression and hypermethylation of FHIT gene were significantly associated with the risk of liver cancer, especially in the Chinese population. Furthermore, the results indicated significant associations between FHIT low expression and TNM-stage, tumor size, and merging of cirrhosis of liver cancer in the Chinese population.

Reduction in the copy number and expression level of the recurrent human papillomavirus integration gene fragile histidine triad (FHIT) predicts the transition of cervical lesions.

Cervical cancer is the second most common cancer and the third leading cause of cancer death in females worldwide, especially in developing countries. High risk human papillomavirus (HR-HPV) infection causes cervical cancer and precancerous cervical intraepithelial neoplasia (CIN). Integration of the HR-HPV genome into the host chromatin is an important step in cervical carcinogenesis. The detection of integrated papillomavirus sequences-PCR (DIPS-PCR) allowed us to explore HPV integration in the human genome and to determine the pattern of this integration. We performed DIPS-PCR for 4 cell lines including 3 cervical cancer cell lines and 40 tissue samples. Overall, 32 HR-HPV integration loci were detected in the clinical samples and the HeLa and SiHa cell lines. Among all the integration loci, we identified three recurrent integration loci: 3p14.2 (3 samples), 13q22.1 (2 samples and a SiHa cell line) and 8q24 (1 sample and a HeLa cell line). To further explore the effect of HR-HPV integration in the 3p14.2 locus, we used fluorescence in situ hybridization (FISH) to determine the copy number of the 3p14.2 locus and immunohistochemistry (IHC) to determine the protein expression levels of the related FHIT gene in the clinical samples. Both the 3p14.2 locus copy number and FHIT protein expression levels showed significant decreases when CIN transitioned to cervical cancer. HPV copy number was also evaluated in these clinical samples, and the copy number of HPV increased significantly between CIN and cervical cancer samples. Finally, we employed receiver operating characteristic curve (ROC curve) analysis to evaluate the potential of all these indexes in distinguishing CIN and cervical cancer, and the HPV copy number, FHIT copy number and FHIT protein expression levels have good diagnostic efficiencies.

Prognostic value of EUS combined with MSCT in predicting the recurrence and metastasis of patients with gastric cancer.

This study aims to explore the prognostic value of endoscopic ultrasonography combined with multi-slice spiral computed tomography in predicting the recurrence and metastasis of gastric cancer, as well as investigate the correlation of fragile histidine triad protein expression with the tumor-node-metastasis stage of gastric cancer patients. A total of 81 gastric cancer patients were selected in our study. All patients were examined by endoscopic ultrasonography and multi-slice spiral computed tomography before operation, and gastric cancer tissues and adjacent normal tissues were obtained after operation. Immunohistochemistry was performed to detect fragile histidine triad expression. All patients were followed up for 3 years after operation. Univariate and multivariate analysis of risk factors were conducted for the prognosis of gastric cancer patients. Endoscopic ultrasonography combined with multi-slice spiral computed tomography could increase the accuracy of preoperative tumor-node-metastasis stage of gastric cancer patients. In gastric cancer tissues, fragile histidine triad expression was mostly weakly positive with a positive rate of 60.5%. In gastric cancer adjacent normal tissues, the positive fragile histidine triad expression was mostly moderate with a positive rate of 79.0%. The fragile histidine triad expression was negatively correlated with tumor-node-metastasis stage of gastric cancer patients. The fragile histidine triad expression decreased along with the increase of T-stage, N-stage and M-stage of gastric cancer patients. Univariate and multivariate analysis showed that T-stage and N-stage were risk factors for the recurrence/metastasis and 3-year mortality of gastric cancer patients, while fragile histidine triad expression was a protective factor. Our study demonstrated that endoscopic ultrasonography combined with multi-slice spiral computed tomography may be more accurate in assessing the preoperative tumor-node-metastasis stage of gastric cancer patients.

Interaction between fragile histidine triad methylation, protein expression and human papillomavirus 16 infection in cervical carcinogenesis

To investigate the association between fragile histidine triad (FHIT) gene methylation, abnormal protein expression and HPV16 infection as well as their interactions in cervical carcinogenesis. A total of 108 patients with normal cervical (NC), 142 cases of cervical intraepithelial neoplasia (CIN1, n=72; CIN2+, n=70), and 100 new cases of cervical squamous cell carcinoma (SCC) were chosen from the Shanxi Tumor Hospital, Second Hospital of Shanxi Medical University, Maternal and Child Health Center in Taiyuan and Jiexiu during September 2009 and March 2011. HPV16 was detected by multiple PCR. FHIT methylation and protein expression levels were detected by methylation specific PCR (MSP) and Western Blot, respectively. All the data were performed with SPSS 20.0 statistical software. Differences among groups were assessed by Chi-square and Kruskal-Wallis tests. The interaction effects were evaluated by additive model. The prevalence rates of HPV16 infection in CIN1 (45.8%), CIN2+(68.6%) and SCC (73.0%) were significantly higher than that in NC (28.7%, P<0.001). In NC, CIN1, CIN2+ and SCC groups, the FHIT gene methylation rates were 3.7%, 13.9%, 21.4% and 38.0% while the protein expression levels were 1.255±0.130, 1.184±0.172, 1.133±0.126 and 1.099±0.148, respectively. Differences among the groups were statistical significant (P<0.001). With increasing degrees of cervical lesions, the HPV16 infection rate (χ(2)=47.623, P<0.001), FHIT methylation rate (χ(2)=40.147, P<0.001) and the rate of FHIT protein low expression (χ(2)=65.098, P<0.001) were all gradually increasing. There appeared positive additive interaction between FHIT methylation, FHIT protein low expression and infection of HPV16. Hypermethylation of FHIT gene, low expression of FHIT protein and HPV16 infection could increase the risk of cervical cancer and precancerous lesions. These results suggested that there might be synergistic action between FHIT gene hypermethylation and HPV16 infection in the progression of cervical cancer and the same was true between the low expression of FHIT protein and HPV 16 infection.

Immunohistochemical characterization of FHIT expression in normal human tissues.

Fragile histidine triad (FHIT) is a tumor suppressor gene that is commonly inactivated in human tumors. Interestingly, the normal pattern of FHIT expression is largely unknown. This study is aimed to characterize the expression of FHIT protein in normal human tissues. A total of 119 normal human tissue specimens were analyzed for the FHIT expression using immunohistochemistry technique. The inclusion criteria included: normal/inflammatory tissue with no evidence of cellular atypia. All studied specimens were stained positively with FHIT and showed either nuclear or cytoplasmic expression. Interestingly, the pattern of FHIT staining was similar among different specimens from each organ. FHIT is located predominantly in the nucleus, although cytoplasmic staining is also present in some cell types. Oral squamous epithelium, breast ductal epithelium, squamous and tubal metaplastic epithelium of the uterine cervix, esophageal squamous epithelium, salivary glands, and bronchial epithelia all strongly expressed the nuclear protein. In connective tissue, FHIT has shown strong cytoplasmic expression in histocytes including macrophages and dendritic cells, fibroblasts, and myofibroblasts. Documentation of the pattern of FHIT expression in normal tissues will contribute to our understanding of the normal function of this protein and to interpretation of potentially altered FHIT expression in human tumors.

Interaction between folate deficiency and aberrant expression related to fragile histidine triad gene in the progression of cervical cancerization

To explore the interaction between folate deficiency and aberrant expression related to fragile histidine triad (FHIT) gene in the progression of cervical cancerization. A total number of 80 patients with histological diagnosis of cervix inflammation (CI), 55 cervical intraepithelial neoplasm I (CIN I), 55 cervical intraepithelial neoplasm II/III (CIN II/III) and 64 cervical squamous cell carcinoma (SCC) were included in this study. Levels of serum folate were detected by microbiological assay method and the methylation status of FHIT gene CpG islands was tested by methylation-specific PCR (MSP). FHIT protein levels were measured by Western blot. In vitro, cervical cancer cell lines CaSki (HPV16-positive) was treated with different concentrations of folate. Proliferation and apoptosis of cells, methylation of FHIT gene and the levels of FHIT protein expression were measured in each group. All analyses were performed with SPSS (version 17.0) statistical software. Differences among groups were assessed by chi-square test, Kruskal-Wallis test. Spearman correlation, and the interaction effects were evaluated by additive model. The levels of serum folate (H = 59.08, P < 0.001) and FHIT protein expression (H = 50.93, P < 0.001) decreased gradually along with the severity of cervix lesions, while the methylation rates of FHIT gene CpG islands increased (trend χ² = 28.34, P < 0.001). Both levels of serum folate levels and FHIT protein expression were positively correlated (r = 0.213, P = 0.001), with an additive interaction seen between them in CIN I, CIN II/III, SCC groups. In vitro, both rates related to proliferation inhibition (r = 0.98, P < 0.001) and apoptosis (r = 0.99, P < 0.001) together with the levels of FHIT protein expression (r = 0.97, P < 0.001) were all increased gradually with the increase of folate concentration while the methylation status of FHIT gene CpG islands all changed from positive to negative gradually. Results from our study revealed that both folate deficiency and FHIT protein aberrant low expression might increase the risk of developing cervical cancer and cervix precancerous lesions, and thus play a synergistic action in the progression of cervical cancerization.

Abnormal FHIT protein expression may be correlated with poor prognosis in gastric cancer: a meta-analysis.

Our current meta-analysis is aimed to investigate the relationships between fragile histidine triad (FHIT) protein expression and prognosis in gastric cancer patients. We searched MEDLINE (1966 ~ 2013), the Cochrane Library Database (Issue 12, 2013), EMBASE (1980 ~ 2013), CINAHL (1982 ~ 2013), Web of Science (1945 ~ 2013), and the Chinese Biomedical Database (CBM) (1982 ~ 2013) without any language restrictions. The meta-analysis was conducted using the STATA 12.0 software. Crude hazard ratios (HR) with its 95 % confidence interval (95 % CI) were calculated. Eight clinical cohort studies with a total of 1,361 gastric cancer patients were involved in our meta-analysis. Our results revealed that FHIT-negative patients exhibited a shorter overall survival (OS) time than FHIT-positive patients (HR = 1.23, 95 % CI = 1.01 ~ 1.44, P < 0.001). Ethnicity-stratified analysis demonstrated that FHIT-negative patients have significantly poorer prognosis than FHIT-positive patients among both Caucasians and Asians (all P < 0.05). In conclusion, our meta-analysis provides evidences that negative expression of FHIT protein may be correlated with poor prognosis in patients with gastric cancer. Thus, FHIT expression level may be utilized as an independent prognostic marker for gastric cancer.

Reduced FHIT Expression Is Associated with Mismatch Repair Deficient and High CpG Island Methylator Phenotype Colorectal Cancer

Colorectal cancer (CRC) is a heterogeneous disease and a major contributor to world cancer mortality rates. Molecular subtypes of CRC have become standards for CRC classification and have established prognostic potential. Here, we attempt to corroborate and provide further insight pertinent to the fragile histidine triad (FHIT) gene in microsatellite instable (MSI), microsatellite stable (MSS), and CpG island methylator phenotype (CIMP) CRC subtypes. We employed array comparative genomic hybridization and multiplex ligation-dependent probe amplification (MLPA) techniques to survey genomic aberrations in FHIT gene and their effects on FHIT protein expression using immunohistochemistry (IHC) in a CRC cohort. We further studied FHIT protein expression by IHC in a larger CRC cohort defined for its mismatch repair (MMR) protein expression and genomic methylation profiles. Our results show FHIT genomic deletions centered in exons 4 and 5 in most of MSI-CRC samples. Moreover, we confirmed the significant association of FHIT protein expression diminution (p=0.035) with MSI-CRC. In the larger cohort, reduced FHIT protein expression was significantly associated with CIMP-high subtype of CRC (p=0.009) and loss of PMS2 protein expression (p=0.017). We conclude that FHIT expression may be a valuable marker for CRC subtyping, and its diagnostic, prognostic, and therapeutic potential should be perused.

Molecular and epigenetic analysis of the fragile histidine triad tumour suppressor gene in equine sarcoids

BackgroundSarcoids are peculiar equine benign tumours. Their onset is associated with Bovine Papillomavirus type -1 or -2 (BPV-1/2) infection. Little is known about the molecular interplay between viral infection and neoplastic transformation. The data regarding papillomavirus infections in human species show the inactivation of a number of tumour suppressor genes as basic mechanism of transformation. In this study the putative role of the tumour suppressor gene Fragile Histidine Triad (FHIT) in sarcoid tumour was investigated in different experimental models. The expression of the oncosuppressor protein was assessed in normal and sarcoid cells and tissue.ResultsNine paraffin embedded sarcoids and sarcoid derived cell lines were analysed for the expression of FHIT protein by immunohistochemistry, immunofluorescence techniques and western blotting. These analyses revealed the absence of signal in seven out of nine sarcoids. The two sarcoid derived cell lines too showed a reduced signal of the protein. To investigate the causes of the altered protein expression, the samples were analysed for the DNA methylation profile of the CpG island associated with the FHIT promoter. The analysis of the 32 CpGs encompassing the region of interest showed no significative differential methylation profile between pathological tissues and cell lines and their normal counterparts.ConclusionThis study represent a further evidence of the role of a tumour suppressor gene in equine sarcoids and approaches the epigenetic regulation in this well known equine neoplasm. The data obtained in sarcoid tissues and sarcoid derived cell lines suggest that also in horse, as in humans, there is a possible involvement of the tumour suppressor FHIT gene in BPV induced tumours. DNA methylation seems not to be involved in the gene expression alteration. Further studies are needed to understand the basic molecular mechanisms involved in reduced FHIT expression.

Clinical significance of FHIT gene and its relationship with clinicopathological feature in cervical carcinoma

：Objective To investigatethe expression fragile histidinetriad (FHIT) protein in cervical carcinoma and itsrelationship with clinicopathological feature of the disease. Methods ImmunohistochemistrySP was used to detect the expression of FHIT protein in 20 cases with chronic cervsis and95 cases with Ⅰ aⅢ b stage cervical carcinomabefore and after treatment. The association of the expression of FHIT withclinicopathological feature was analyzed by the statistical method. Results There weresignificant differences between FHIT expression and histological grades and types oftissue, lymph node metastasis and invade depth (P ＜0.05). FHIT expression wasnot correlated with age and clinical stage (P ＞0.05). There were significantdifferences in FHIT protein expression levels in the patients with cervial cancer betweenbefore-after radiotherapy and the levels before radiotherapy was lower then those afterradiotherapy (P ＜0.05). There was positively correlated in FHITprotein expression rates before and after radiotherapy (P ＜0.05). There were significantcorrelation between FHIT expression and 3-year survival rate, the positive rates of theexpression FHIT protein higher then negative ones (P ＜0.05). Conclusion FHIT protein has great reference valuethat could be as a parameter for evaluating biological action and predicting the prognosisof cervical cancer. Key words: Uterine cervical neoplasms; Genes, tumor suppressor; ,Pathology, clinical

Expression and clinical significance of fragile histidine triad gene and inhibitor of apoptosis protein in cervical tissue

Objective To study the expression of fragile histidine triad (FHIT)and.survivin in normal cervix, cervical intraepithelial neoplasia(CIN) and cervical cancer. To discuss the potential involvement of FHIT and survivin in tumorigenesis, metastasis in cervical cancer; to discuss the significance of FHIT and survivin in early diagnosis of cervical cancer. Methods The expressions of FHIT protein and survivin were detected by immunohistochemistry in 20 cases of normal cervix, 20 cases of CIN Ⅰ ,25 cases of CIN Ⅱ/Ⅲ ,60 cases of cervical cancer. Results The percentages of negative expression of FHIT protein in normal tissues were 0% (0/20),24.4% ( 11/45 ) in CIN group, 10.0% (2/20) in CIN Ⅰ group, 36.0% ( 9/25 ) in CIN Ⅱ / Ⅲ group and 66.7%(40/60) in cervical cancer group. There were significant differences between groups (Chi-square test, P ＜0.05 ). The positive expression rate of survivin wase 20.0% ( 4/20 ) in normal group, 31.1% ( 14/45 ) in CIN group,and 95.0% (57/60)in cervical cancer group. There was significant difference between groups (Chisquare test, P ＜ 0.05 ). FHIT protein expression and survivin expression were negatively related ( P＜ 0.05 ) in CIN and cervical cancer. Conclusion Since the expression level of FHIT is associated with the grade of CIN, it can be used to screen or forecasting higher-grade-group of CIN. FHIT and survivin has clinical reference value for screening and early diagnosis of cervical lesions and cervical cancer. Key words: Cervical intraepithelial neoplasia (CIN)Cervical carcinoma; Fragile histidine triad (FHIT); Survivin; Immunohistochemistry; Early diagnosis

Fragile histidine triad (FHIT) gene promoter methylation and protein expression in mycosis fungoides.

Objective To detect the FHIT gene promoter methylation and protein expression in mycosis fungoides(MF).Methods Tissue specimens were collected from 48 patients with MF and 18 normal human controls.FHIT protein expression was determined by immunohistochemistry,and methylation status of FHIT gene by methylation-specific PCR.Results Abnormal methylation of FHIT gene was found in 26(54.2%)out of the 48 specimens.Thirty(63.5%)specimens of MF were negative for FHIT protein,which was observed in all the control specimens.The promoter methylation of FHIT was closely correlated with the protein expression of FHIT,but unrelated to the sex of,tumor staging or lymph node metastasis in patients with MF.Conclusion The FHIT gene promoter methylation may contribute to the inactivation and abnormal expression of FHIT protein in MF. Key words: Lymphoma,T-cell; Methylation; Promoter regions(genetics); Genes

Expression of FHIT Protein in Lung Cancer by Cell Array.

Fragile histidine triad (FHIT) is a candidate tumor suppressor gene. Aberrance of FHIT has been observed in multiple carcinomas induced by environmental carcinogens, especially in lung cancer. In this study, the expression of FHIT protein in cell array was detected to further development of cell array and for a rapid, simple, and economical method. The lung cancer samples were collected from the Tianjin Medical University General Hospital, the First Central Hospital and the Tianjin Chest Hospital from May to August in 2005. A total of 112 dots cell array were constructed in this study including the pleural fluid of 50 cases of lung cancer and 6 cases of normal, the cell array was done with the home-made cell array survey setting. Immunohistochemical stains were performed. All points rank in a good order without distortion in cell array. After IHC stains of FHIT, the number of cells did not decrease. The positive expression was totally the same to that from the tissue microarry. Cell array is a rapid and high-throughput technique with high specificity, which could be broadly used in the clinical diagnosis and the screen of epidemilology.

Expression of FHIT gene in cervical carcinoma

Objective To investigate the expression of fragile histidine triad (FHIT) gene in cervical carci-noma and relationship with its clinical-pathological implication. Methods The expression of FHIT was detected by immunohistochemistry SP method in 42 cases of cervical carcinoma and 13 cases of adjacent tissue. Results 47.6% (20 of 42) of cases expressed FttIT in the tumor cells,and 92.3% (12 of 13) of cases of the adjacent tissue were present. There was a significant positive correlation between cervical carcinoma and adjacent tissue(P <0.01). The positive rates of FHIT in high and middle desrees of differentiation were significantly higher than that in low degree of differentiation(54.2% vs 38.9%). Tumors with lymph node metastases(45.9%) had loss FHIT protein expression than those without metastasis(60.0%) (P <0.05). The FHIT expression between Ⅰ and Ⅱ stage,the difference was significant(55.0% vs 45.5%) (P < 0.05). Conclusion FHIT gene plays an improtant role in the occurrence and development of cervical carcinoma. It is suggested that FHIT can be a useful marker for predicting invasion and metas-tasis ability of cervical carcinoma. Key words: Cervical neoplasms; Immunohistochemistry; Fragila histidlne triad

Aberrations of the FHIT Gene and Fhit Protein in Canine Lymphoma Cell Lines

The fragile histidine triad (FHIT) gene is a tumor-associated gene, and aberrant FHIT gene and protein expression have been described in many types of human tumors. Furthermore, it has been reported that FHIT gene inactivation is induced by hypermethylation of 5' CpG islands in the gene or by genomic deletion around the open reading frame (ORF). In this study, we explored the aberrations in the canine FHIT gene and Fhit protein expression and assessed the methylation status and genomic deletions by using 5 canine lymphoma cell lines. We found that the decrease in the expression of the Fhit protein in canine lymphoma cell lines was similar to that in human tumors. The expression of the wild-type FHIT transcript was reduced in all 5 cell lines. However, we could not confirm the involvement of aberrant methylation events in the 5' CpG islands of the canine FHIT gene. We were able to identify homozygous or heterozygous deletions in the canine FHIT genes in all 5 cell lines. Moreover, a widespread genomic deletion of the FHIT gene, which included the ORF region, was detected in 1 cell line. In the present study, we detected aberrations in the FHIT gene and Fhit protein expression in all 5 canine lymphoma cell lines, and this phenomenon might be an important factor in promoting canine lymphoma.