FHIT expression in neoplastic, hyperplastic, and normal endometrium

Fragile histidine triad (FHIT), a candidate of tumor suppressor protein, expression was examined on paraffin-embedded specimens in proliferative, secretory, hyperplastic, and neoplastic human endometrium by immunohistochemistry. The results of FHIT immunoreactivity in endometrial carcinomas were compared with prognostic indicators as well as with p53 overexpression. Forty-four cases of endometrial carcinoma, 30 normal functional (15 proliferative, 15 secretory), and 24 hyperplastic endometrium (12 without atypia, 12 with atypia) specimens were studied using polyclonal FHIT antibody. The streptavidin-biotin-peroxidase detection system was used, and the intensity and the distribution of immunoreactivity were evaluated semiquantitatively. There were no significant differences in FHIT expression in the proliferative, secretory, hyperplastic, either with or without atypia, or carcinomatous endometria. No significant difference in FHIT expression of endometrial carcinomas was detected when prognostic parameters or p53 overexpression were considered. Loss or reduced FHIT expression was not found to predict disease-free or cumulative survivals. This study showed that loss or reduction in FHIT protein expression is present in normal functional and hyperplastic endometria as well as in neoplastic endometrium. FHIT protein seems not to be involved directly in endometrial carcinogenesis, but rather, it regulates cell proliferation both in physiologic and in pathologic conditions of endometrium.     

FHIT基因杂合性丢失及微卫星不稳定性与宫颈癌发生发展的关系

目的探讨FHIT基因杂合性丢失(LOH)及微卫星不稳定性(MI)在宫颈癌发生发展中的作用。方法选择FHIT基因的两个微卫星多态标记对60例浸润性宫颈癌及35例宫颈上皮内瘤样病变(CIN)组织进行LOH和MI检测。结果在D3S1234和D3S1300座位上,浸润性宫颈癌的LOH发生率分别为45.0%(27/60)、38.3%(23/60),MI频率分别为18.3%(11/60)、11.7%(7/60)。CIN的LOH频率分别为42.9%(15/35)、37.1%(13/35)。MI频率分别为11.4%(4/35)、8.6%(3/35)。宫颈癌及CIN在两个位点的LOH和MI无统计学差异(P>0.05);两位点的LOH阳性率在宫颈癌组织高中分化与低分化之间有统计学差异(P<0.05);双座位的LOH及MI在宫颈癌有无淋巴结转移间有统计学差异(P<0.05);高级别CIN(CIN及原位癌)患者的LOH和MI的发生率高于低级别CIN(CIN、)。结论FHIT基因的改变是CIN发生过程中的较晚期事件;FHIT基因的LOH对于宫颈癌的筛查、早期诊断及判断预后可能具有临床实用价值。     

结直肠癌中FHIT蛋白的异常表达及其临床意义

目的探讨结直肠癌中脆性组氨酸三联体(FH IT)基因蛋白表达状况与临床病理指标的关系。方法采用半定量免疫印迹(W estern b lot)检测30例结直肠癌及其癌旁正常组织(≥5 cm)FH IT蛋白表达状况。结果30例癌组织有56.7%的FH IT蛋白表达异常,FH IT蛋白表达量与患者的年龄、性别、肿瘤部位、肿瘤大小及组织学类型无关(P>0.05)而与肿瘤的组织分化程度、浸润深度、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,FH IT蛋白低表达越明显。结论FH IT蛋白表达状况可能与结直肠癌组织学分级、浸润程度、Dukes分期及淋巴结转移相关,提示FH IT蛋白表达降低可能对结直肠癌发生、发展具有重要作用。     

four weeks were examined. Results: Th

ifference between super lizer group and comparison group(P>0.05),but there was significant difference between the obove two groups and hyperthermia group or teletherapy group( P<0.01). Conclusion: VX_2 carcinoma replanted obviously changes cell's immunity.The treated effect of teletherapy is better than hyperthermia. Teletherapy can obviously change the course of immunity.Super lizer have no effect on VX_2 carcinoma.radiotherapy;teletherapy;hyperthermia;super lizer     

肺癌前病变、肺癌中FHIT基因表达的临床研究

背景与目的FHIT基因为近年发现的新的候选抑癌基因，位于3p14．2，跨越FRA3B易脆点，在包括肺癌在内的多种人类肿瘤中均存在异常表达。本研究旨在观察FHIT基因在人肺癌前病变、肺癌中的表达情况，探讨FHIT基因在肺癌发生、发展过程中的可能作用。方法采用免疫组化方法检测298例甲醛固定、石蜡包埋的标本（包括161例肺癌、51例肺癌前病变、30例正常肺组织、23例肺良性病变和33例肺癌转移淋巴结）中FHIT蛋白表达情况。结果FHIT蛋白在正常肺组织及肺良性病变组织中均无失表达，癌前病变组织和肺癌组织中失表达率分别为54．9％（28／51）和59．0％（95／161），肺癌转移淋巴结组织中失表达率为78．8％（26／33）；肺癌前病变、肺癌及转移淋巴结组织中FHIT蛋白失表达率显著高于正常肺组织及肺良性病变组织（P〈0．001）。肺癌组织中FHIT基因表达水平与肺癌组织学类型、肿瘤细胞分化程度、患者pTNM分期、淋巴结转移有密切关系（P〈O．05）。FHIT蛋白失表达组肺癌患者的术后5年生存率显著低于表达组（P〈0．01）。吸烟组患者FHIT基因失表达率69．1％显著高于无吸烟组49．5％（P〈0．01）。结论FHIT蛋白失表达可能是肺癌发生过程中的早期分子事件，与肺癌的发生、发展及预后有关；吸烟导致FHIT蛋白表达下降可能是诱发肺癌的原因之一。     

肺癌组织中FHIT基因蛋白的表达缺失与吸烟的关系

目的；研究脆性组氨酸三联体（FHIT）基因蛋白在肺癌组织中的表达及其与吸烟的关系。方法：运用免疫组织化学SP法检测56例外科切除的肺癌组织中FHIT蛋白的表达。结果：56例肺癌组织中33例（58.9%)显示FHIT蛋白缺失。肺鳞癌（SqCCs)中FHIT蛋白缺失率明显高于非鳞癌（non-SqCCs)(72.7% vs39.1%;x^2=6.32,P=0.012)；而且吸烟患者中FHIT蛋白缺失率明显高于非吸烟者（67.5%Vs37.5%;x^2=4.25,P=0.039）。结论：FHIT蛋白的表达缺失是肺癌中的常发事件，尤其在肺鳞癌和吸烟者中。FHIT蛋白的表达可以作为肺癌诊断的一个标志物，FHIT基因可能在吸烟相关的肺癌形成过程中起一定作用。     

喉癌组织中FHIT基因蛋白表达的研究

目的:以喉鳞状细胞癌为研究对象,探讨FHIT基因蛋白表达在喉癌发生、发展中的作用及临床意义.方法:用免疫组织化学SP法检测52例喉癌组织、23例癌旁组织及10例正常组织中FHIT基因蛋白的表达,分析在不同临床病理指标下FHIT蛋白表达的情况.结果:FHIT蛋白在正常组织中的阳性表达率(90.0%)及癌旁组织中的阳性率(78.3%)均高于癌组织中的阳性率(46.2%),差异有统计学意义(均P＜0.01).癌组织FHIT蛋白阳性表达率与临床分期和颈淋巴结转移有关,与病理分级无关.结论:喉癌的发生、发展与FHIT抑癌基因的失活有密切关系,FHIT基因很可能是喉癌重要的侯选抑癌基因.     

Expression of common chromosomal fragile site genes, WWOX/FRA16D and FHIT/FRA3B is downregulated by exposure to environmental carcinogens, UV, and BPDE but not by IR

Common chromosomal fragile sites are unstable genomic loci susceptible to breakage, rearrangement, and are highly recombinogenic. Frequent alterations at these loci in tumor cells led to the hypothesis that they may contribute to cancer development. The two most common chromosomal fragile sites FRA16D and FRA3B which harbor WWOX and FHIT genes, respectively, are frequently altered in human cancers. Here we report that environmental carcinogens, ultraviolet (UV) light, and Benzo[a]pyrene diol epoxide (BPDE), significantly downregulate expression of both genes. On the other hand, we observe that ionizing radiation (IR) does not affect expression of these genes, suggesting that the effect of repression exerted by UV and BPDE is not just a consequence of DNA damage but may be a result of different signaling pathways triggered by specific DNA lesions. Such downregulation correlates with an induction of an S-phase delay in the cell cycle. Treatment of UV-irradiated cells with caffeine abrogates the S-phase delay while concomitantly overcoming the repression phenomenon. This suggests the involvement of unique cell cycle checkpoint mechanisms in the observed repression. Therefore, it is hypothesized that protracted downregulation of the putative tumor suppressor genes WWOX and FHIT by environmental carcinogens may constitute an additional mechanism of relevance in the initiation of tumorigenesis.