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.

Decreased fragile histidine triad expression in colorectal cancer and its association with apoptosis inhibition

AIM： To detect the expression of fragile histidine triad （FHIT） in normal colorectal tissue, colorectal adenoma and colorectal cancer （CRC） tissue, and to analyze its relationship with the clinicopathological features of CRC, and apoptosis-associatecl proteins （Bcl-2, Bax, survivin） and apoptosis in colorectal cancer. METHODS： FHIT mRNA analysis was performed by nested reverse transcription-polymerase chain reaction （RT-PCR） assay. Tissue microarray （TMA） was established to detect the expression of FHIT, Bcl-2, Bax and survivin genes in 80 CRC tissue specimens, 16 colorectal adenoma tissue specimens and 16 hemorrhoid （PPH） tissue specimens during the same period of time as the control. Citrate-microwave-SP was used as immunohistochemical method. The relationship between clinicopathological factors, such as differentiation grades and 5-year survival rate was observed. TUNEL assay was used to detect the apoptosis index in 80 CRC tissue specimens. RESULTS： Ten out of 26 （38.5%） CRC tissue specimens expressed aberrant FHIT transcripts, none of the aberrant FHIT transcripts was observed in the matchednormal tissue and colorectal adenoma tissue by nested RT-PCR assay. The positive rate of FHIT gene expression in normal colorectal tissue, colorectal adenoma and carcinoma tissue was 93.75%, 68.75% and 46.25%, respectively. Clinicopathological analysis of patients showed that the decreased FHIT gene expression was not associated with age, sex, serum CEA levels, tumor site and size, histological classification. However, the expression of FHIT was correlated with differentiation grades, pathological stages, lymph node metastases and 5-year survival rate after operation. The positive rate of apoptosis-associated proteins （Bax, Bcl-2 and survivin） in CRC tissue was 72.50%, 51.25% and 77.50%, respectively. The expression of these apoptosisassociated proteins in CRC tissue was correlated with the expression of FHIT. The mean apoptosis index in FHIT negative tumors was significantly lower than that in FHIT- positive tumors （5.41 ± 0.23 vs 0.56 ± 0.10, P 〈 0.01）. CONCLUSION： The FHIT gene plays an important role in the regulation of apoptosis and decreased FHIT expression plays a key role in the initiation and progression of colorectal carcinoma.

Aberrant crypt focus and fragile histidine triad protein in sporadic colorectal carcinoma

AIM:To characterize aberrant crypt focus (ACF) in adjoining mucosa in sporadic colorectal carcinoma and to evaluate fragile histidine triad (Fhit) protein and Ki67. METHODS:ACF was identified grossly and classified histologically in 75 resected specimens. ACF was typed into hyperplastic ACF (HACF) and dysplastic ACF (DACF). Sections of ACF, carcinoma and normal colonic mucosa as control were studied for Fhit and Ki67 expressions by immunohistochemistry and were grouped according to staining intensity and the number of positive stained cells observed in different histological groups. Comparison was done between the different groups by Pearson's χ 2 test and γ test for the ordinal data. P value < 0.05 was considered as significant.RESULTS:Age range was 40 to 86 years in males (mean = 43.36) and 45 to 70 years in females (mean = 56). HACF was identified in all cases studied in the non-tumorous colonic mucosa; ACF was observed as non-contiguous scattered foci, which supports the hypothesis of acquisition of single focus monoclonality by colonic epithelial cells in tumor generation. Twenty-four (32%) had DACF and were observed as closure to carcinoma foci. Intensity of Fhit expression:(1) HACF 40% exhibited strong intensity, similar to normal, moderate in 36% and weak in 24%; (2) DACF strong in 25%, moderate in 37.5% and weak in 37.5%; and (3) carcinoma negative in 16%, strong in 43% and moderate and weak in 28.5% each. Significant difference was observed in intensity of the Fhit protein expressions by HACF and DACF (P < 0.05). Tumor in older patients showed a stronger Fhit intensity compared to younger patients (P = 0.036). Vegetarian diet intake and nonsmokers showed stronger Fhit intensities. Advanced stage tumor, non-vegetarian diet and younger age was associated with loss of Fhit protein. Ki67 positivity was an extended crypt pattern in HACF and DACF showed extension up to the neck region of the crypts and surface epithelium. Carcinomas showed a marked increase in Ki67 expression (P < 0.05). Fhit protein had an inverse association with Ki67 expression. CONCLUSION:Weaker Fhit intensity was associated with smoking, non-vegetarian diet intake and increasing Ki67 expression. Loss of Fhit protein expression is possibly influenced by environmental factors like smoking and non-vegetarian diet intake.

Effect of fragile histidine triad gene transduction on proliferation and apoptosis of human hepatocellular carcinoma cells

AIM:To evaluate the inhibitory effects of human fragile histidine triad(FHIT) gene on cell proliferation and apoptosis in human hepatocellular carcinoma line Hep3B in vitro. METHODS:A recombinant pcDNA3.1(+) /FHIT including the functional region of FHIT gene was constructed and transferred into human hepatocellular carcinoma cells in vitro. mRNA and protein expression of the FHIT gene in the transfected cells was detected by RT-PCR and Western blot,respectively. The effect of FHIT on proliferation was detected by MTT assay. Changes in cell cycle and apoptosis were assayed by flow cytometry. Five mice received subcutaneous transplantation of Hep3B-FHIT;5 mice received subcutaneous transplantation of normal Hep3B and Hep3B-C as controls. The body weight of nude mice and tumor growth were measured. RESULTS:RT-PCR and Western blot analysis showed that the expression level of FHIT-mRNA and FHIT protein was higher in Hep3B cells after infection withpcDNA3.1(+) /FHIT. The growth of Hep3B cells treated with pcDNA3.1(+) /FHIT was significantly inhibited. The pcDNA3.1(+) /FHIT-transfected Hep3B cells showed a significantly higher cell rate at G0-G1 phase and increased apoptosis in comparison with controls(P < 0.05) . The growth of transplanted tumor was inhibited markedly by FHIT. Tumors arising from the Hep3B-FHIT cells occurred much later than those arising from the Hep3B and Hep3B-C cells. The growth of Hep3B-FHIT cells was slow and the tumor volume was low. CONCLUSION:Transduction of FHIT gene inhibits the growth of human hepatocellular carcinoma cells and induces cell apoptosis in vivo and in vitro.

Fragile histidine triad gene alterations are not essential for hepatocellular carcinoma development in South Korea

AIM: To establish the role of FHIT in the pathogenesis hepatocellular carcinoma (HCC). METHODS: We examined genomic alterations, as well as, mRNA and protein expression patterns from the FHIT gene, in 48 surgically resected hepatocellular carcinoma (HCC) tissues. Additionally, p53 mutations were analyzed. RESULTS: Aberrant FHIT transcripts were detected in 11 of 48 surrounding non-tumor liver tissues and 27 of 48 HCC samples (22.9% vs 56.3%, P = 0.002). No point mutations were identified within the open reading frame region of FHIT. Loss of heterozygosity (LOH) of the FHIT locus was detected in 4 of 42 informative cases for D3S1300, and 3 of 29 informative cases for D3S1313. Reduced expression of FHIT protein (Fhit) was observed in 8 (16.7%) of 48 HCC samples, with complete loss of Fhit in only 1 case. There were no associations with abnormal transcripts, LOH, and Fhit expression. p53 mutations were identified in 9 of the 48 HCC cases. However, none of the cases displayed a G to T transversion at p53 codon 249. CONCLUSION: Aberrant FHIT transcripts were more common in HCC tissues as compared to non-cancerous liver tissues. However, Fhit expression was lost or reduced in a minor fraction of HCC tissues, while it was strongly expressed in non-cancerous liver tissues.Therefore, our study suggests that FHIT plays a role in relatively few HCC cases in South Korea.

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.

Loss of fragile histidine triad and amplification of 1p36.22 and 11p15.5 in primary gastric adenocarcinomas

AIM: To investigate the genomic copy number alterations that may harbor key driver genes in gastric tumorigenesis. METHODS: Using high-resolution array comparative genomic hybridization (CGH), we investigated the genomic alterations of 20 advanced primary gastric adenocarcinomas (seventeen tubular and three mucinous) of Chinese patients from the Jilin province. Ten matching adjacent normal regions from the same patients were also studied. RESULTS: The most frequent imbalances detected in these cancer samples were gains of 3q26.31-q27.2, 5p, 8q, 11p, 18p, 19q and 20q and losses of 3p, 4p,18q and 21q. The use of high-resolution array CGH increased the resolution and sensitivity of the observed genomic changes and identified focal genetic imbalances, which included 54 gains and 16 losses that were smaller than 1 Mb in size. The most interesting focal imbalances were the intergenic loss/homozygous deletion of the fragile histidine triad gene and the amplicons 11q13, 18q11.2 and 19q12, as well as the novel amplicons 1p36.22 and 11p15.5. CONCLUSION: These regions, especially the focal amplicons, may harbor key driver genes that will serve as biomarkers for either the diagnosis or the prognosis of gastric cancer, and therefore, a large-scale investigation is recommended.

EXPRESSION OF FRAGILE HISTIDINE TRIAD AND P53 IN NON-SMALL CELL LUNG CANCER

Objective： To investigate the expression offragile histidine triad （FHIT） and p53 protein in non-small cell lung cancer （NSCLC） and explore the relationship between their expressions and the clinicopathological features. Methods： FHIT protein and p53 protein were detected by immunohistochemistry in 76 cases of NSCLCs and matched normal lung tissues. Results： Fifty-one cases （67.1%） showed negative expression of FHIT （apparent reduction or loss） and thirty-seven cases （48.7%） showed p53 positive expression （overexpression）. The difference was significant （P=0.04）. However, there was no significant difference in FHIT expression between the p53-positive group and the p53-negative group （64.9% versus 69.2%, P=0.686）. The negative rate of FHIT protein expression was higher in squamous cell carcinoma than in adenocarcinoma, in moderately and poorly differentiated carcinoma than in well-differentiated carcinoma, and in cases with smoking history than in cases without smoking history （P〈0.05）. There was no relationship between FHIT expression and clinical stage or lymph node metastasis. The negative FHIT expression was not an independent predictor of overall survival （P=0.338）. Conclusion： The frequency of negative expression of FHIT protein is higher than that of positive expression of p53 in NSCLCs. The negative expression of FHIT is independent of the expression of p53. The change of expression of FHIT may play a role in the smoking related lung tumorigenesis while it may have no relationship with the progress of NSCLC or prognosis of the patients.

Interaction between fragile histamine triad and protein kinase C alpha in human non-small cell lung cancer tissues

Objective To investigate the interaction between fragile histamine triad (FHIT) and protein kinase C alpha (PKCα) in human non-small cell lung cancer tissues. Methods FHIT and PKCα double positive samples were screened by immunohistochemical staining from 13 human non-small cell lung cancer tissues. Co-immunoprecipitation was performed by using anti-FHIT and anti-PKCα. The immune precipitate was analyzed by SDS-PAGE and Western blot. Results Immune precipitate staining detection showed that 3 samples out of the 13 cases were double positive for FHIT and PKCα. FHIT protein was present in the immune precipitate of anti-PKCα while there was PKCα in the immune precipitate of anti-FHITmAb. Conclusion FHIT and PKCα exist as a complex in human non-small cell lung cancer tissues, which will provide a new route for studying the pathogenesis and immunotherapy of human non-small cell lung cancer.

EGFR Mutation and FHIT Methylation: Inverse Relationship in Patients with Lung Adenocarcinoma and Tuberculosis

Objective:To investigate the genetic correlations between epithelial growth factor receptor(EGFR)mutation and FHIT methylation in patients diagnosed with lung adenocarcinoma(AC)and pulmonary tuberculosis(TB).Methods:The presence of EGFR mutations and the methylation status of the FHIT gene in patients presenting with AC and TB were analyzed.The correlation between TB status and the observed genetic and epigenetic variations was also examined.Results:Among the 90 patients included in the study,38 exhibited EGFR mutations(14 among those with TB and 24 among those without TB),while 29 exhibited FHIT myelination(19 among those with TB and 10 among those without TB).Furthermore,the protein expression levels of EGFR and FHIT were significantly higher in patients diagnosed solely with AC compared to those presenting with both AC and TB.A robust inverse correlation was identified between TB status and the frequency of EGFR mutation(P<0.001).Moreover,significant associations were observed between TB status and FHIT methylation(P<0.01).Conclusion:The findings suggest a correlation between TB and the prevalence of EGFR mutation and FHIT methylation in the pathogenesis of AC.

Expression of Ki-67, galectin-3, fragile histidine triad, and parafibromin in malignant and benign parathyroid tumors

Background It is widely recognized that the diagnosis of parathyroid carcinoma （PC） is often difficult because of the overlap of characteristics between malignant and benign parathyroid tumors, especially at an early stage. Our study aimed to investigate the differential expression of Ki-67, galectin-3, fragile histidine triad （FHIT） gene, and parafibromin in PC, parathyroid adenoma （PA）, parathyroid hyperplasia （PH）, and normal parathyroid （NP） tissues; then to assess these expression values for use in differential diagnosis of malignant and benign parathyroid tumors. Methods Data of 15 cases with PC, 19 PAs, and 8 PHs were retrospectively analyzed for their clinical characteristics. The expression of Ki-67, galectin-3, FHIT, and parafibromin were detected via immunohistochemistry in the above-mentioned specimens and 6 NPs as control. Results Complete loss of parafibromin expression was seen in 9 of 15 （60%） carcinomas, and all normal parathyroid tissues and parathyroid benign tumors stained positive for parafibromin except for one （4%） adenoma. Galectin-3 staining was positive in 11 of 15 （73%） carcinomas, 5 of 19 （26%） adenomas, 1 of 8 （12%） hyperplasias, and 0 of 6 normal tissues. The Ki-67 proliferative index was high in 4 of 15 （27%） carcinomas, 1 of 19 （5%） adenomas, and none of the hyperplasia or normal tissues. FHIT expression did not differ appreciably among the tumor types. The combination of overexpression of galectin-3 or loss of parafibromin increased sensitivity for PC to 87%, while the specificity of both positive galectin-3 and positive Ki-67 could reach 100%. Conclusions These data suggested that loss of parafibromin and overexpression of galectin-3 and Ki-67 might help to distinguish parathyroid carcinoma from other parathyroid tumors. And the combination of two or three of these markers might produce better sensitivity and/or specificity for the diagnosis of parathyroid carcinoma.

河北省磁县食管癌高发区食管鳞状细胞癌组织HPV检测及FHIT表达的研究

背景与目的:河北省磁县是食管癌高发区,有关人乳头状瘤病毒(humanpapillomavirus,HPV)感染和当地食管癌发生的关系尚无研究报道。本研究旨在探讨HPV感染在当地食管癌发生中的病因学意义,同时分析与环境致癌物密切相关的脆性组氨酸三联体基因(fragilehistidinetriad,FHIT)表达与HPV感染的关系。方法:收集河北省磁县食管癌高发区128例和非高发区24例食管鳞状细胞癌石蜡包埋组织,用PCR进行HPV检测,用免疫组化方法分析FHIT在蛋白水平上的表达情况,同时分析HPV感染和FHIT异常表达的关系。结果:PCR检测结果表明,河北省食管癌高发区食管鳞状细胞癌组织中HPV检出率为20.3%,略高于非高发区(8.3%),但两者差别无显著性(P>0.05)。免疫组化结果显示,食管癌高发区食管鳞癌组织中FHIT基因异常表达率(75.6%)明显高于非高发区食管鳞癌组织(54.2%,P<0.05)。食管癌组织中HPV感染和FHIT的异常表达之间无明显相关性。结论:河北省食管癌高发区食管癌组织FHIT的异常表达率明显高于非高发区病例。

FHIT和MDM2在口腔黏膜下纤维性变及其癌变组织中的表达

目的:初步探讨脆性组氨酸三联体基因(fragile histidine triad,FHIT)、原癌基因MDM2在口腔黏膜下纤维性变(oral submucous fibrosis,OSF)和癌变过程中的作用。方法:采用免疫组织化学SP法检测44例OSF组织、15例OSF癌变组织及10例正常口腔黏膜组织中FHIT和MDM2蛋白的表达及分布。结果:FHIT在正常口腔黏膜中强阳性表达,在OSF及OSF癌变组织中阳性表达率逐渐减少,OSF组及OSF癌变组织组显著低于正常对照组(P<0.05);OSF癌变组织组显著低于OSF组(P<0.05)。MDM2蛋白在正常口腔黏膜中呈阴性表达,在OSF及OSF癌变组织中阳性表达率逐渐增加,OSF组及OSF癌变组织组显著高于正常对照组(P<0.05),OSF癌变组织组显著高于OSF组(P<0.05)。结论:FHIT表达下调和缺失,以及MDM2过度表达可能在OSF癌变过程中具有重要作用。

宫颈癌组织中FHIT基因5'端CpG岛甲基化及其与基因失活的关系

背景与目的:脆性组氨酸三联基因(fragile histidine triad gene,FHIT)作为抑癌基因与多种实体瘤的发生有关,并在多种肿瘤中因甲基化而失活。本研究拟探讨宫颈癌组织中FHIT基因5'端CpG岛甲基化状况及其与基因失活的关系。方法:采用甲基化特异性聚合酶链反应(methylation鄄specificPCR,MSP)和免疫组织化学法分别检测10例正常宫颈鳞状上皮、40例宫颈癌组织中FHIT基因5'端CpG岛的甲基化发生状况和FHIT蛋白表达情况。结果:(1)正常宫颈鳞状上皮组织中未发现存在FHIT基因甲基化状态,而宫颈癌组织中FHIT基因5'端CpG岛的甲基化率为40.0%(16/40);(2)临床Ⅱ期宫颈癌病例中FHIT基因甲基化的发生率为56.5%(13/23),明显高于Ⅰ期的14.3%(2/14)(P<0.05);(3)宫颈癌组织中存在FHIT蛋白表达降低或缺失,阳性率仅为30.0%(12/40),显著低于正常宫颈组织的100.0%(10/10)(P<0.05)。结论:FHIT基因5'端CpG岛甲基化是宫颈癌中该基因失活的机制之一,可能与宫颈癌的发生发展有关。

喉鳞癌组织中FHIT表达与细胞增殖、转移的关系

背景与目的:脆性组氨酸三联体(fragilehistidinetriad,FHIT)基因定位于染色体3pl4.2,跨越大多数人类基因组的共同脆性部位FRA3B,为一候选的抑癌基因,在包括头颈部鳞状细胞癌在内的许多人类恶性肿瘤中都存在FHIT基因的异常。本研究的目的为探讨喉鳞癌(laryngealsquamouscellcarcinoma,LSCC)组织中FHIT基因蛋白的表达及其与肿瘤细胞增殖与转移的关系。方法:采用免疫组化S法,检测41例喉鳞癌组织及其相对应的喉切缘非癌组织中FHIT、PCNA的表达。结果:非癌组织和喉鳞癌组织中,FHIT阳性率分别为100%(41/41)和46.3%(1941)(P<0.01)。喉鳞癌中,在TNM分期Ⅰ～Ⅱ期和Ⅲ～Ⅳ期组,FHIT阳性率分别为69.6%和16.7%;淋巴结转移阳性和阴性组分别为20.0%和61.5%。以上两组比较均有显著性差异(P<0.05)。非癌和喉鳞癌组织中,PCNA标记指数分别为(9.98±2.34)%和(50.71±13.64)%,两者有极显著性差异(P<0.01)。喉鳞癌中,FHIT与PCNA表达有明显的负相关关系(P<0.05)。结论:FHIT低表达与喉鳞癌细胞增殖及淋巴结转移有关。

散发性结直肠癌组织中FHIT、MSH2蛋白的异常表达及其临床意义

背景与目的:脆性组氨酸三联体(fragilehistidinetriad,FHIT)蛋白表达缺失是胃肠道肿瘤的频发事件,但在大肠癌却有争议;最近研究表明FHIT蛋白表达失活可能是错配修复蛋白,尤其是mutS同种组织蛋白2(mutShomolog2,MSH2)改变的结果。本研究旨在探讨FHIT、MSH2蛋白在散发性结直肠癌(sporadiccolorectalcarcinoma,SCC)组织中的表达情况及其临床意义。方法:采用免疫组化SP法检测手术切除的84例SCC及其对应癌旁正常结直肠组织和23例肠腺瘤组织标本中FHIT、MSH2蛋白的表达。结果:FHIT蛋白在SCC组织、结直肠腺瘤组织、癌旁正常结直肠组织中阳性率分别为48.81%、73.91%和100%,三者的阳性率差异有显著性(P<0.05)。FHIT蛋白表达水平与SCC患者的年龄、性别及肿瘤部位、组织学类型无关(P>0.05),而与肿瘤浸润深度、分化程度、Dukes分期和淋巴结转移有关(P<0.05),在浸润深度越深、分化程度越低、Dukes分期越晚和有淋巴结转移的癌组织中,FHIT蛋白低表达就越明显;而MSH2蛋白表达水平仅与Dukes分期有关(P<0.05)。SCC中FHIT蛋白表达与MSH2蛋白表达呈正相关(r=0.3728,P<0.01)。结论:(1)FHIT蛋白表达水平与SCC的恶性程度有关,可作为预测SCC浸润转移潜能的一项有意义的生物学指标;(2)SCC中FHIT、MSH2蛋白表达二者之间呈正相关。

FHIT基因在胃癌中的甲基化表达及其与胃癌临床病理特征的关系

目的探讨胃癌(GC)组织中脆性组氨酸三联体(FHIT)基因的甲基化表达及其与胃癌临床病理特征的关系。方法选取我院胃镜检查诊断为胃癌的74例患者及36例慢性胃炎患者为研究对象。应用甲基化特异性PCR(MSP)检测两组胃黏膜中FHIT基因的甲基化状态,对比相应的病理特征并进行分析。结果胃癌组与对照组组织中FHIT基因甲基化阳性率分别为51.4%及5.6%,胃癌组FHIT基因甲基化阳性率显著高于对照组(P<0.05),且甲基化表达与GC患者的年龄、性别、肿瘤大小、部位及组织学类型无关(P>0.05),与病变的浸润深度、淋巴结转移和远处转移有关(P<0.05)。结论 FHIT基因甲基化修饰参与胃癌的发生发展过程,可反映胃癌侵袭转移的程度。

宫颈癌中抑癌基因FHIT表达与HPV16基因状态

目的：探讨抑癌基因FHIT表达及人乳头瘤病毒16（HPV16）的基因型整合状态在宫颈癌发生发展中的作用及相关性。方法：选取柳州市人民医院2013年6月至2014年12月收治的42例宫颈癌、55例宫颈上皮内瘤样病变（CIN）和20例宫颈正常组织的患者,免疫组化法检测宫颈组织中FHIT蛋白表达;多重PCR法检测HPV16 E2/E7表达。结果：FHIT蛋白的总阳性表达率为57.26%（67/117）,正常宫颈组织、CINⅠ、CINⅡ、CINⅢ和宫颈癌中FHIT蛋白阳性率分别为85.00%、80.00%、75.00%、60.00%和26.19%。随着宫颈病变加重,FHIT蛋白阳性表达率下降,组间差异有统计学意义（χ^2=7.335;P=0.003）。117例单纯HPV16阳性标本HPV16总整合率为81.20%,正常宫颈组织、CINⅠ、CINⅡ、CINⅢ和宫颈癌中整合率分别为60.00%、66.67%、75.00%、95.00%和92.86%;随病变加重,整合率增强,组间差异有统计学意义（χ^2=5.713,P=0.003）;FHIT蛋白阳性表达在不同HPV16整合时不同,差异有统计学意义（χ^2=11.989,P=0.000）。结论：HPV16基因整合可能通过诱导FHIT基因低表达从而促使宫颈癌发生发展。

FHIT和Ki-67在CIN、宫颈癌中的表达及意义

目的:探讨脆性组氨酸三联体(FHIT)和Ki67在宫颈上皮内瘤样病变(CIN)和宫颈癌中的表达情况。方法:采用免疫组化检测二者在正常和病变宫颈组织中的表达。结果:①FHIT的异常表达率和Ki67LI随着宫颈肿瘤的进展逐渐增加。②Ki67与宫颈癌的组织学级别、肌层浸润和淋巴结转移有关。③FHIT在宫颈癌中的表达与Ki67不相关。结论:①FHIT和Ki67与宫颈癌的发生发展有关。②FHIT可能不参与细胞周期的调控。

Survivin、Fhit蛋白在喉癌组织中的表达及临床意义

目的观察喉癌组织中存活素(Survivin)、脆性组氨酸三联体基因(fragile histidine traid,Fhit)的表达,探讨Fhit与Survivin在喉癌组织中的相关性。方法 2006年10月—2007年8月、2008年7月—2013年12月手术治疗并病理证实的92例喉鳞癌标本及相应癌旁组织(距离癌边缘10 mm),25例喉正常黏膜,采用免疫组化链霉卵白素-生物素复合体(SABC法)检测Survivin、Fhit蛋白的表达。结果 Survivin在喉癌组织中的阳性率明显高于癌旁及喉正常黏膜组织(P<0.05),与临床分期有关(P<0.05),与年龄、淋巴结转移、分化程度无关(P>0.05)。Fhit蛋白在喉癌组织中的阳性率明显低于癌旁及喉正常黏膜组织,差异有统计学意义(P<0.05),与临床分期和淋巴结转移有关(P<0.05),与年龄、分化程度无关(P>0.05)。Fhit与Survivin呈负相关(P<0.05)。结论 Survivin蛋白高表达和Fhit蛋白低表达在喉癌的发生、发展上可能有协同作用。联合检测可能成为喉癌新的分子指标。