非小细胞肺癌p53、FHIT、K-RAS基因突变与吸烟相关性Meta分析

目的：从循证医学的角度对非小细胞肺癌患者p53、FHIT、K-RAS基因突变异常表达与吸烟相关性进行Meta分析。方法：检索中国学术期刊网全文数据库（CNKI）、中国科技期刊数据库（维普资讯网）、美国国立图书馆PubMed数据库,美国临床肿瘤学会（ASCO）论文集,辅以手工检索;检索时间段为1990年-2010年。检索出p53、FHIT、K-RAS基因突变与吸烟关系研究的文献197篇,最终符合纳入标准的文献26篇。对纳入文献进行方法学质量评价,采用Meta分析专用软件Review Manager 5.0进行统计分析。结果：共纳入26个研究,分别对有相同统计内容且可以合并统计的p53、FHIT、K-RAS基因突变与吸烟关系合并OR值并计算95%CI。分别为：吸烟人群p53基因突变率较高,表现为低表达,[OR=3.50,95%CI（2.45-5.00）,总体效应检验Z=6.88,P〈0.0001];吸烟人群K-RAS基因突变率明显偏高,表现为高表达,[OR=4.50,95%CI（3.00-6.75）,总体效应检验Z=7.26,P〈0.0001];吸烟人群FHIT基因突变率较高,表现为低表达,[OR=2.99,95%CI（1.01-8.88）,总体效应检验Z=1.98,P=0.005]。结论：吸烟与p53、FHIT、K-RAS基因突变率呈正相关,其中p53、FHIT基因高表达为保护性因素,K-RAS基因高表达为危险因素。     

三阴性乳腺癌中p53蛋白表达的Meta分析

目的:评价三阴性乳腺癌与p53蛋白表达的相关性,为提高三阴性乳腺癌个体化治疗提供参考。方法:通过PubMed、Web of Science、CNKI、WanFang data、VIP数据库检索相关文献,检索时间为2005年至2020年。由两位研究者按照文献的纳入与排除标准进行文献筛选、资料提取、质量评价,最后采用RevMan 5.3软件进行Meta分析。结果:纳入文献36篇,其中中文文献29篇,英文文献7篇。结果显示:三阴性乳腺癌组p53的阳性表达率高于非三阴性乳腺癌组［OR=2.29,95%CI(2.06,2.55)］,p53阳性组的淋巴转移率高于p53阴性组［OR=1.96,95%CI(1.20,3.18)］,差异具有统计学意义;而p53的阳性表达与三阴性乳腺癌的TNM分期无关［OR=0.49,95%CI(0.08,2.90)］,差异没有统计学意义;三阴性乳腺癌p53阳性组的总生存率低于p53阴性组［OR=0.36,95%CI(0.23,0.56)］,差异具有统计学意义;三阴性乳腺癌p53阳性组的无病生存率低于p53阴性组［OR=0.32,95%CI(0.23,0.45)］,差异具有统计学意义;三阴性乳腺癌患者的年龄与p53的阳性表达没有相关性［OR=1.17,95%CI(0.83,1.65)］,差异没有统计学意义。结论:p53的表达与三阴性乳腺癌的发生、发展及预后密切相关,并且可能成为预测三阴性乳腺癌发生发展的独立因子。     

中国食管癌患者p53基因改变与吸烟、饮酒的Meta分析

目的 探讨吸烟、饮酒与中国人群食管癌p53基因改变的关系。方法 在Medline和CNKI数据库中系统检索相关文献,应用Meta分析的方法进行定量综合分析。结果 共纳入14篇文献,累积食管癌2 108例,p53基因改变1 142例,平均阳性率为54.2%。在中国人群中,吸烟与食管癌p53基因改变的合并OR值为1.61(95% CI:1.09-2.38),P=0.003;饮酒与食管癌p53基因改变的合并OR值为1.91(95% CI:1.44-2.53),P＜0.001。结论 中国人群中,吸烟、饮酒均与食管癌p53基因改变有显著联系。     

乳腺癌组织p53表达与新辅助化疗疗效相关性Meta分析

目的评价乳腺癌组织p53的表达与新辅助化疗疗效的相关性,为乳腺癌的规范化和个体化治疗提供依据。方法计算机检索Cochrane、PubMed、Embase、中国知网、万方和维普等数据库2000-04-2013-11乳腺癌组织p53表达与新辅助化疗的临床研究,按照一定的入排标准将研究方法相似的文献归类整理,原始数据汇总后进行Meta分析和统计处理。结果共纳入22篇相关临床研究,p53表达阳性762例,其中有效478例;p53表达阴性1 094例,其中有效762例。Meta分析结果显示,乳腺癌组织p53表达阳性组与阴性组新辅助化疗的有效率差异无统计学意义,OR=0.69,95%CI:0.44~1.09,P=0.11。亚组分析显示,在蒽环类基础化疗(OR=0.65,95%CI:0.24~1.76,P=0.40)和紫杉类联合化疗(OR=0.70,95%CI:0.40~1.25,P=0.23)中,p53表达的阳性与阴性组间乳腺癌新辅助化疗疗效的差异均无统计学意义;但统一免疫组化阳性标准p53≥10%,则发现p53表达的阳性与阴性组间乳腺癌新辅助化疗有效率差异有统计学意义,OR=0.49,95%CI:0.29~0.82,P=0.006。结论 p53作为乳腺癌新辅助化疗疗效敏感性的指标,只有统一免疫组化阳性标准p53≥10%后,对乳腺癌新辅助化疗疗效才可能有预测作用。     

乳腺癌易感基因突变对前列腺癌易感性的影响

目的:用 Meta 分析评价乳腺癌易感基因（BRCA）突变对前列腺癌易感性的影响。方法:通过计算机检索PubMed、Embase、Cochrane图书馆、Web of Science、Springer Link等数据库,对纳入的研究运用Revman 5．3软件以及stata 14.0软件进行 Meta 分析。结果:共纳入 23 篇文献, 共 47 726 例患者, 其中BRCA1基因突变人群5 745例,BRCA2基因突变人群5 127例。Meta 分析结果显示:BRCA1基因对前列腺癌易感性(OR:1.62,95%CI:0.83～3.15,P=0.16)、Gleason评分(OR:1.39,95%CI:0.89～2.15,P=0.15)、T分期(OR:0.84,95%CI:0.44～1.58,P=0.59)、总生存时间(OR:1.12,95%CI:0.64～1.95,P=0.69)无统计学差异;在BRCA2基因对前列腺癌易感性(OR:2.24,95%CI:1.70～3.44,P＜0.000 01)、Gleason评分(OR:4.34,95%CI:3.06～6.15,P＜0.000 01)、T分期( OR:2.33,95%CI:1.09～4.96,P=0.03)、总生存时间(OR:1.53,95%CI:1.37～1.71,P＜0.000 01)有显著性差异。结论:BRCA2基因突变的人群患前列腺癌的风险以及预后明显比非突变人群的要高。     

p27Val109Gly基因多态性与肿瘤易感性的Meta分析

目的:通过Meta分析系统评价p27Val109Gly基因多态性与肿瘤易感性的关系。方法:检索PubMed、Medline、Web of Science和中国知网等数据库中研究p27Val109Gly基因多态性与肿瘤易感性关系的研究。运用Rev-Man5.0软件进行异质性检验、系统性评价和分层亚组分析,计算合并OR及95%CI;应用State 11.0软件进行定量发表偏倚检验。结果:共纳入13项研究,累计病例组4 894例,对照组5 413例。G等位基因携带者肿瘤总体易感性降低,OR=0.81,95%CI=0.66～0.99,P=0.04,尤其是前列腺癌(OR=0.60,95%CI=0.36～0.98,P=0.04)和食管癌(OR=0.34,95%CI=0.22～0.55,P<0.01)。剔除不符合或不能进行HWE检验的研究后,再次行Meta分析。结果显示,G等位基因与肿瘤易感性无相关性,OR=0.82,95%CI=0.64～1.03,P=0.09。高加索人群(OR=0.97,95%CI=0.84～1.12,P=0.67)和亚洲人群(OR=0.77,95%CI=0.57～1.02,P=0.07)、基于医院(OR=0.70,95%CI=0.42～1.17,P=0.17)和社区(OR=0.86,95%CI=0.67～1.11,P=0.24)的肿瘤患者,p27Val109Gly基因多态性与肿瘤易感性无明显相关性。结论:p27Val109Gly基因多态性G等位基因与肿瘤的易感性呈负相关,尤其是前列腺癌和食管癌。这种相关性在高加索人、亚洲人及对照组来源于医院或社区的患者中不显著。     

XRCC1 Arg399Gln位点多态性与乳腺癌易感性的Meta分析

[目的]评估X射线交叉互补修复基因1(X-ray repair cross complementing protein 1,XRCC1)基因Arg399Gln位点单核苷酸多态性与高加索及亚洲人群乳腺癌(breast cancer,BC)易感性的关系。[方法]检索Pub Med、Embase、中国期刊全文数据库(CNKI)、万方数据库、中国生物医学文献数据库(CBM)和中文科技期刊全文数据库(VIP)等数据库,获取有关XRCC1 Arg399Gln位点多态性与高加索及亚洲人群乳腺癌易感性关系的病例对照研究的资料,以病例组及对照组XRCC1 Arg 399Gln等位基因分布的比值比(OR)为效应指标,应用Meta分析软件Review Manager(version 5.0.10)对各研究原始数据进行统计处理及异质性检验,计算合并OR值及其95%可信区间。[结果 ]共纳入24项病例对照研究,包括15151例乳腺癌患者和17179例对照。Meta分析结果显示,XRCC1 Arg399Gln位点Gln/Gln突变型可能会增加亚洲人群乳腺癌的发病风险[Gln/Gln vs.Arg/Arg亚洲组:OR=1.20(95%CI:1.03~1.39),P=0.02;Gln/Gln vs.Arg/Arg+Arg/Gln亚洲组:OR=1.20(95%CI:1.04~1.38),P=0.01。Gln/Gln vs.Arg/Arg OR=1.01(95%CI:0.94~1.09),Z=0.35,POR=0.73;Gln/Gln+Arg/Gln vs.Arg/Arg OR=1.02(95%CI:0.95~1.09,Z=0.58,POR=0.56;Gln/Gln vs.Arg/Arg+Arg/Gln OR=1.01(95%CI:0.95~1.08),Z=0.33,POR=0.74)。[结论]XRCC1 Arg399Gln位点Gln/Gln突变型可能与亚洲人群乳腺癌易感性相关。     

中国非吸烟人群被动吸烟与肺癌关系的meta分析

背景与目的 本研究旨在探讨中国非吸烟人群被动吸烟与肺癌的关系.方法 通过计算机检索Medline、PubMed、CENTRAL(theCochrane central register of controlled trials)、中国生物医学文献数据库系统(CBM)、中国期刊全文数据库(CNKI)、中文科技期刊全文数据库(VIP)等收集国内外1987年-2007年间公开发表的关于中国非吸烟人群被动吸烟与肺癌的研究文献,应用统计软件Stata 11.0进行数据分析,计算其合并优势比(odds ratio,OR)和95%置信区间(confidence interval,CI).采用Begg和Eggr法对发表偏倚进行量化检测.结果 纳入分析的文章共有16篇,合并分析结果表明:中国非吸烟人群被动吸烟与肺癌的关系有统计学意义(OR=1.13,95%CI:1.05-1.21,P=0.001).每日被动吸烟≥20支、成年时期被动吸烟、非吸烟女性被动吸烟、被动吸烟暴露于工作环境等与肺癌的发生关系具有统计学意义,P值、OR值及95%CI分别为:P=0.000 3、OR=1.78、95%CI: 1.30-2.43,P=0.000 1、OR=1.50、95%CI:1.23-1.83,P=0.000 7、OR=1.50、95%CI: 1.19-1.90,P＜0.000 1、OR=1.41、95%CI:1.19-1.66.结论 中国非吸烟人群中,被动吸烟是肺癌发生的一个重要危险因素,尤其是暴露量≥20支/日、成年时期被动吸烟、女性、工作环境的被动吸烟与肺癌的发生关系密切.     

IL-10基因-592C>A多态性与宫颈癌易感性的Meta分析

目的:系统评估IL-10基因-592C>A多态性与宫颈癌易感性。方法:计算机检索Pubmed、EBSCO、Web of Science、中国知网、万方等数据库,搜集关于IL-10基因-592C>A多态性与宫颈癌易感性的相关研究文献。遵循文献纳入和排除标准,采用RevMan5.2软件进行Meta分析,计算、合并OR值及95%CI,最后进行偏倚分析和敏感性分析。结果:共纳入9篇文献,累计病例2 913例,对照2 037例。Meta分析结果显示,IL-10基因-592C>A多态性与宫颈癌总体发病风险之间未见显著关系(AA+CA vs CC:OR=0.92,95%CI=0.68~1.26,P=0.62;A vs C:OR=1.01,95%CI=0.82~1.23,P=0.95;AA vs CC:OR=1.04,95% CI=0.65~1.64,P=0.88;AA vs CA+CC:OR=1.08,95%CI=0.82~1.43,P=0.58;CA vs CC:OR=0.9,95%CI=0.67~1.19,P=0.45)。根据人群进行亚组分析结果显示,该基因多态性与亚洲人群及西方人群宫颈癌发病风险均无明显相关性（P>0.05）。结论:IL-10基因-592C>A多态性与宫颈癌易感性可能无关。     

PD-L1表达与肝内胆管细胞癌临床病理特征关系的Meta分析

目的 探讨PD-L1表达与肝内胆管细胞癌(iCCA)临床病理特征的关系。方法 全面检索PubMed、Embase、Web Of Science、万方数据库、CNKI(中国知网)数据库，自建库以来至2022年4月有关PD-L1表达与肝内胆管细胞癌临床、病理特征(包括预后信息)的文献，并根据制定纳入、排除标准筛选文献。使用Review Manager 5.4与Stata 16.0软件进行Meta分析。结果 共纳入中英文文献9篇、总计1585例患者。Meta分析发现PD-L1表达与肝内胆管细胞癌的患者性别(OR=1.45,95%CI:1.10～1.91)、TNM分期(OR=0.48,95%CI:0.35～0.66)、淋巴结转移(Lymphatic metastasis)(OR=2.73,95%CI:1.04～7.14)、肝硬化(OR=1.39,95%CI:1.02～1.89)、乙肝抗原(OR=1.62,95%CI:1.16～2.27)有相关性。结论 PD-L1的表达与肝内胆管细胞癌的临床病理特征具有相关性。     

Primary cervical carcinomas show 2 common regions of deletion at 3P, 1 within the FHIT gene: evaluation of allelic imbalance at FHIT, RB1 and TP53 in relation to survival

Chromosome arm 3p is re-arranged in many tumor types, including cervical carcinomas. Putative tumor-suppressor genes on 3p have been proposed, including the FHIT gene, which maps to chromosome band 3p14.2. We have analyzed 79 primary cervical carcinomas for allelic imbalance (AI) at 17 chromosome 3 loci, including 3 within the FHIT gene. Expression of the FHIT gene was evaluated after immunohistochemistry with an antibody against the pFHIT protein. Previously determined human papillomavirus status, defined after in situ hybridization, showed type 16 or 18 in 56/77 tumors. Tumors were also analyzed for AI at loci within the RB1 (chromosome band 13q14.2) and the TP53 (17p13) genes for AI. AI was found at 1 or more 3p loci in 50/79 tumors, at frequencies ranging from 30% to 52% at the individual loci. Two smallest regions of overlapping deletion (SROs) were found, 1 including parts of the FHIT gene (SRO flanked by D3S1481 and D3S1313) and another more distal SRO between D3S32 and D3S1286. FHIT protein expression was reduced in 57/69 (83%) tumors but not associated with AI at FHIT loci (p = 0.56). AI was found in TP53 and RB1 in 18% and 29% of the samples, respectively. Relapse-free survival was associated with AI in the TP53 gene in both a univariate (p = 0.0003) and a multivariate (p = 0.004) analysis. This study confirms a high frequency of AI at chromosome arm 3p in primary cervical carcinomas. The AI results and the reduced FHIT protein staining indicate that FHIT alterations are important in cervical carcinogenesis.     

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.     

脆性组氨酸三联体基因在宫颈癌前病变和宫颈癌中的表达及其与p53和HPV16/18的关系

目的 探讨脆性组氨酸三联体（FHIT）基因缺失与p53的过度表达和人乳头状瘤病毒16和（或）18（HPV16／18）感染在宫颈癌前病变（CIN）和宫颈癌（CC）发生发展中的作用和意义。方法 采用免疫组化SP法检测52例CIN和69例CC中的FHIT基因和p53的表达,以原位杂交方法检测HPV16／18感染情况,并以18例正常宫颈组织作为对照。结果 FHIT在正常宫颈组织（正常组）中呈阳性表达;FHIT在宫颈CIN组中的阴性率为30．8％,在CINⅢ期的表达,明显高于正常组和CINⅠ、Ⅱ期（P〈0．01）;在CC组中阴性率为66．7％（46／69）,明显高于正常组和CIN组（P〈0．01）,且随细胞分化的降低,FHIT阴性率上升。p53和HPV16／18在CC组的阳性率分别达56．5％（39／69）和84．1％（58／69）,均高于CIN和正常组（P〈0．05）,且CC组的p53阳性率随细胞分化的降低而升高（P〈0．01）。CIN和CC组的FHIT阳性和阴性者,p53阳性率差异均无统计学意义（P〉0．05）,相关性分析也显示无相关关系;但两组FHIT阴性者的HPV16／18感染率明显高于FHIT正常表达者（P〈0．01）,FHIT与HPV呈负相关关系。结论 FHIT基因缺失与宫颈癌发生有关,它在CIN中的缺失可能可作为高危型CIN人群的筛选和宫颈癌早期诊断指标。CIN和CC中的FHIT缺失常与p53过度表达同时存在,但两者间无相关性。HPV16／18可能是引起FHIT和p53异常的共同原因。     

Genetic alterations in poorly differentiated endocrine carcinomas of the gastrointestinal tract

BACKGROUND: The molecular pathogenesis of poorly differentiated endocrine carcinomas of the gastrointestinal tract (GI PDECs) remains unclear. It has been suggested that these lesions either originate from multipotent stem cells that also can serve as the origin of nonendocrine adenocarcinomas or arise due to the dedifferentiation of well-differentiated endocrine carcinomas (WDECs). METHODS: Ten gastric and 9 colorectal PDECs, 9 gastric WDECs, and 12 colorectal carcinomas (CRCs) were analyzed for loss of heterozygosity (LOH) at 11q13 (MEN1), 17p13.1 (p53), 3p14.2 (FHIT), 3p21.3 (RASSF1A), and 18q23 (DCC/DPC4/Smad2), and for immunohistochemical expression of p53, FHIT, Rb, and p16. RESULTS: PDECs exhibited high fractional allelic loss (FAL; 0.49), with frequent (> 40%) alterations in p53, Rb, MEN1, FHIT, and 18q. No significant differences were found between gastric and colorectal PDECs. Gastric WDECs also exhibited high FAL (0.44), with frequent alterations in Rb and/or p16, MEN1, and 3p21. CRCs exhibited a low level of FAL (0.23), with frequent (> 50%) p16 and p53 alterations. When gastric PDECs and WDECs were compared, substantial similarities were found with respect to FAL (0.42 vs. 0.44) and with respect to individual gene alterations, except in p53, which was consistently altered only in PDECs. CRCs, which were characterized by a lower FAL (0.56 vs. 0.23) and which lacked alterations in both 3p and Rb, were found to be significantly different from colorectal PDECs. CONCLUSIONS: GI PDECs demonstrated a high level of chromosomal instability; consistent inactivation of both the p53 and p16/Rb pathways; and frequent LOH at 3p (possibly involving FHIT), the MEN1 locus, and 18q. The profile of genetic alterations in PDECs was more consistent with the profile in WDECs than with the profile in CRCs.     

Loss of heterozygosity at loci of candidate tumor suppressor genes in microdissected primary non-small cell lung cancer

To investigate the etiological association of allelic loss at chromosomal regions containing tumor suppressor genes (TSGs) in non-small cell lung cancer (NSCLC) in Taiwan, we examined 48 microdissected NSCLC samples for loss of heterozygosity (LOH) at nine loci where TSGs are localized nearby. The associations of LOH at each locus with clinicoparameters and prognosis were also examined. The frequent LOH was observed using markers, D3S1285 near the FHIT gene (58.3%), D17S938 near the p53 gene (56.7%), D9S925 near the p16 gene (54.5%), and D13S153 near the RB gene (47.6%). The occurrence of LOH at each TSG locus was compared with the patients' clinicoparameters. The incidence of LOH at D17S938 (p53 gene) and D3S4545 (VHL gene) was significantly higher in squamous carcinoma tumors than in adenocarcinoma tumors (P = 0.003 and 0.024, respectively). LOH of these two loci also occurred frequently in tumors from smoker patients compared to that from nonsmoker patients (P = 0.013 and 0.025, respectively). LOH at D13S153 (RB gene) was also associated with smoking (P = 0.008). In addition, the prognostic analyses indicated that the patients with LOH at D18S535 (18q21, near the SMAD2/4 gene) had significantly longer post-operative survival time compared to those without LOH (P = 0.03). Our results suggested that LOH at FHIT, p53, and p16 genes may occur frequently in NSCLC patients in Taiwan. In addition, LOH at p53, RB, and VHL may associate with smoking or squamous carcinoma patients and LOH at SMAD2/4 may be correlated with better prognosis.     

Frequent polymorphic variations but rare tumour specific mutations of the S100A2 on 1q21 in non-small cell lung cancer

Contrary to the recent hypothesis that S100A2 is a tumour suppressor, no somatic mutations have yet been identified. We therefore screened 90 non-small cell lung carcinoma (NSCLC) samples, initially for mutations in S100A2 and then also for mutations in P53 and K-RAS genes. Alterations were detected in 46.7% of squamous lung cancer (SCC) samples, but we detected only one novel tumour specific mutation, Q23X in squamous carcinoma. We detected four polymorphisms, two of them published for the first time (144+109 C/G and 297+75A/G) and two already published: S62N, in the coding region and related to squamous cell carcinoma (SCC), and 297+17T/C. Analysis of S100A2 expression revealed that expression in adenocarcinomas and squamous cell carcinomas is significantly different, but not related to any of the found alterations. In one tumour with S62N polymorphism, P53 and K-RAS genes were also mutated, while two tumours with the Q23X mutation have a P53 but no K-RAS mutation. To the best of our knowledge, this is the first report describing alterations in the S100A2 gene proving a relation between changes in predominantly squamous lung cancer.     

Clinicopathological significance of the fragile histidine triad transcription protein expression in laryngeal carcinogenesis

The fragile histidine triad (FHIT), frequently lost in many cancers, was identified as a candidate tumor suppressor gene at chromosome 3p locus 14.2. Loss of the FHIT protein because of the alteration or loss of heterozygosity by genetic deletion occurs in a variety of epithelial tumors including head and neck cancer. However, the biological function of the FHIT protein is still unknown and its role in intrinsic cellular proliferation remains particularly controversial in preinvasive lesions and invasive tumors of the head and neck. To clarify the role of the FHIT protein in laryngeal squamous cell carcinoma (LSCC) and to examine whether the expression of FHIT could be a prognostic parameter for laryngeal carcinogenesis, we investigated the relationship between the expression of the FHIT protein, other tumor suppressor gene products (p53 and p16), the cellular proliferation marker (Ki-67) and the survival time of patients with LSCC. In our study, there were significant differences (p<0.05) in the expression of FHIT between low grade dysplasia and LSCC. Additionally, survival time analysis showed a significant correlation between the reduction of FHIT expression and the length of disease-free survival (p<0.05) in patients with T1-T2 N0 laryngeal carcinoma. However, we did not confirm a relationship between the expression of FHIT, the other tumor suppressor gene products (p53 and p16) or the cellular proliferation marker (Ki-67). In conclusion, we provided evidence that the reduction of FHIT levels may be a useful prognostic indicator for the clinical outcome of laryngeal SCC. Our findings indicated that FHIT utilizes a pathway independent of p53 and is involved in abnormal cell proliferation via the breakdown of G0-G1 arrest in the larynx and apoptosis during multistep carcinogenesis of the larynx.