Values of mutations of K-ras oncogene at codon 12 in detection of pancreatic cancer:15-year experience

AIM:To summarize progress in the study of K-ras gene studies in pancreatic cancer and its potential clinical significance in screening test for early detection of pancreatic cancer,and to differentiate pancreatic cancer from chronic pancreatitis in recent decade.METHODS:Literature search (MEDLINE 1986-2003) was performed using the key words K-ras gene, pancreatic cancer, chronic pancreatitis, and diagnosis. Two kind of opposite points of view on the significance of K-ras gene in detection early pancreatic cancer and differentiation pancreatic cancer from chronic pancreatitis were investigated.The presence of a K-ras gene mutation at codon 12 has been seen in 75-100% of pancreatic cancers, and is not rare in patients with chronic pancreatitis, and represents an increased risk of developing pancreatic cancer. However,the significance of the detection of this mutation in specimens obtained by needle aspiration from pure pancreatic juice and from stools for its utilization for the detection of early pancreatic cancer, and differentiation pancreatic cancer from chronic pancreatitis remains controversial.CONCLUSION:The value of K-ras gene mutation for the detection of early pancreatic cancer and differentiation pancreatic cancer from chronic pancreatitis remains uncertains in clinical pratice. Nevertheless, K-ras mutation screening may increase the sensitivity of FNA and ERP cytology and may be useful in identifying pancreatitis patients at high risk for developing cancer, and as a adjunct with cytology to differentiate pancreatic cancer from chronic pancreatitis.

Detection of point mutation in K-ras oncogene at codon 12 in pancreatic diseases

AIM:To investigate frequency and clinical significance of K-ras mutations in pancreatic diseases and to identify its diagnostic values in pancreatic carcinoma.METHODS:117 ductal lesions were identified in the available sections from pancreatic resection specimens of pancreatic ductal adenocarcinoma, comprising 24 pancreatic ductal adenocarcinoma, 19 peritumoral ductal atypical hyperplasia, 58 peritumoral ductal hyperplasia and 19 normal duct at the tumor free resection margin. 24 ductal lesions were got from 24 chronic pancreatitis. DNA was extracted.Codon 12 K-ras mutations were examined using the two-step polymerase chain reaction (PCR) combined with restriction enzyme digestion,followed by nonradioisotopic single-strand conformation polymorphism (SSCP) analysis and by means of automated DNA sequencing.RESULTS: K-ras mutation rate of the pancreatic carcinoma was 79%(19/24) which was significantly higher than that in the chronic pancreatitis 33%(8/24) (P<0.01). It was also found that K-ras mutation rate was progressively increased from normal duct at the tumor flee resectbn margin, peritumoral ductal hyperplasia, peritumoral ductal atypical hyperplasia to pancreatic ductal adenocardnoma. The mutation pattern of K-ras 12 codon of chronic pancreatitis was GGT→GAT, GGT and CGT,which is identical to that in pancreatic carcinoma.CONCLUSION:K-ras mutation may play a role in the malignant transformation of pancreatic ductal cell. K-ras mutation was not specific enough to diagnose pancreatic carcinoma.

Promoter hypermethylation of tissue specific tumor supressor genes and point mutation in K-ras, c-myc proto-oncogenes in urinary (transitional cell) bladder carcinoma

In a total of 83 UN specimens were investigated for proto-oncogene mutations, tumor supressor genes promoter methylation status and c-myc and Ki-67 expression. Point mutations in c-myc were detected in cases with high grade and proliferation index. Mutated K-ras proto-onco- gene profiles were detected in 17 (21%) tumoral spiecemens that examined. Tumor specimens were also showed hypermethylated promoter domain for the SFRP2, MGMT tumor supressor genes. These findings showed the combine effect of mutated c-myc and K-ras oncogene and epigenetic inactivation of tissue specific tumor supressor genes (TS) play a crucial role in tumor progression and recurrence in UN carcinogenesis.

Tanshinone ⅡA improves Alzheimer’s disease via RNA nuclearenriched abundant transcript 1/microRNA-291a-3p/member RAS oncogene family Rab22a axis

BACKGROUND Alzheimer’s disease(AD)is a neurodegenerative condition characterized by oxidative stress and neuroinflammation.Tanshinone ⅡA(Tan-ⅡA),a bioactive compound isolated from Salvia miltiorrhiza plants,has shown potential neuroprotective effects;however,the mechanisms underlying such a function remain unclear.AIM To investigate potential Tan-ⅡA neuroprotective effects in AD and to elucidate their underlying mechanisms.METHODS Hematoxylin and eosin staining was utilized to analyze structural brain tissue morphology.To assess changes in oxidative stress and neuroinflammation,we performed enzyme-linked immunosorbent assay and western blotting.Additionally,the effect of Tan-ⅡA on AD cell models was evaluated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Genetic changes related to the long non-coding RNA(lncRNA)nuclear-enriched abundant transcript 1(NEAT1)/microRNA(miRNA,miR)-291a-3p/member RAS oncogene family Rab22a axis were assessed through reverse transcription quantitative polymerase chain reaction.RESULTS In vivo,Tan-ⅡA treatment improved neuronal morphology and attenuated oxidative stress and neuroinflammation in the brain tissue of AD mice.In vitro experiments showed that Tan-ⅡA dose-dependently ameliorated the amyloid-beta 1-42-induced reduction of neural stem cell viability,apoptosis,oxidative stress,and neuroinflammation.In this process,the lncRNA NEAT1-a potential therapeutic target-is highly expressed in AD mice and downregulated via Tan-ⅡA treatment.Mechanistically,NEAT1 promotes the transcription and translation of Rab22a via miR-291a-3p,which activates nuclear factor kappa-B(NF-κB)signaling,leading to activation of the pro-apoptotic B-cell lymphoma 2-associated X protein and inhibition of the anti-apoptotic B-cell lymphoma 2 protein,which exacerbates AD.Tan-ⅡA intervention effectively blocked this process by inhibiting the NEAT1/miR-291a-3p/Rab22a axis and NF-κB signaling.CONCLUSION This study demonstrates that Tan-ⅡA exerts neuroprotective effects in AD by modulating the NEAT1/miR-291a-3p/Rab22a/NF-κB signaling pathway,serving as a foundation for the development of innovative approaches for AD therapy.

The role of tazarotene-induced gene 1 in carcinogenesis:is it a tumor suppressor gene or an oncogene?

Tazarotene-induced gene 1(TIG1)is induced by a derivative of vitamin A and is known to regulate many important biological processes and control the development of cancer.TIG1 is widely expressed in various tissues;yet in many cancer tissues,it is not expressed because of the methylation of its promoter.Additionally,the expression of TIG1 in cancer cells inhibits their growth and invasion,suggesting that TIG1 acts as a tumor suppressor gene.However,in some cancers,poor prognosis is associated with TIG1 expression,indicating its protumor growth characteristics,especially in promoting the invasion of inflammatory breast cancer cells.This review comprehensively summarizes the roles of the TIG1 gene in cancer development and details the mechanisms through which TIG1 regulates cancer development,with the aim of understanding its various roles in cancer development.

K-ras基因突变与胃癌组织病理特征及预后的相关性分析

目的 探讨与分析K-ras基因突变与胃癌组织病理特征及预后的相关性。方法 选取100例胃癌患者作为胃癌组,选择同期在本院体检的健康人群100例作为对照组,检测所有对象的外周血K-ras基因突变情况。调查胃癌患者的组织病理特征,随访患者的预后并进行相关性分析。结果 胃癌组的K-ras基因突变率显著高于对照组,差异有统计学意义(P<0.05)。在胃癌组中,不同胃癌组织病理特征(病灶直径、组织学分化、临床分期、淋巴结转移)患者的K-ras基因突变率对比差异均有统计学意义(P<0.05)。胃癌患者平均随访时间(35.59±1.19)月,其中死亡18例,死亡患者的K-ras基因突变率显著高于生存患者,差异有统计学意义(P<0.05)。在胃癌组中,Spearman分析显示K-ras基因突变率与病灶直径、组织学分化、临床分期、淋巴结转移、预后死亡等存在正相关性(P<0.05)。结论 胃癌患者多伴随有血清K-ras基因突变,与患者的临床病理特征与预后死亡存在相关性,K-ras基因突变具有重要的临床应用价值。

Concomitant epidermal growth factor receptor mutation/c-ros oncogene 1 rearrangement in non-small cell lung cancer: A case report

BACKGROUND Epidermal growth factor receptor(EGFR)mutation and c-ros oncogene 1(ROS1)rearrangement are key genetic alterations and predictive tumor markers for non-small cell lung cancer(NSCLC)and are typically considered to be mutually exc-lusive.EGFR/ROS1 co-mutation is a rare event,and the standard treatment appr-oach for such cases is still equivocal.CASE SUMMARY Herein,we report the case of a 64-year-old woman diagnosed with lung adenocar-cinoma,with concomitant EGFR L858R mutation and ROS1 rearrangement.The patient received two cycles of chemotherapy after surgery,but the disease prog-ressed.Following 1-month treatment with gefitinib,the disease progressed again.However,after switching to crizotinib,the lesion became stable.Currently,crizotinib has been administered for over 53 months with a remarkable treatment effect.CONCLUSION The efficacy of EGFR tyrosine kinase inhibitors and crizotinib was vastly different in this NSCLC patient with EGFR/ROS1 co-mutation.This report will aid future treatment of such patients.

结直肠癌APC、K-ras、p53基因突变检测

目的:探讨结直肠癌中APC、K-ras、p53基因突变模式。方法:应用酚/氯仿法提取48例结直肠癌组织及其相应正常黏膜组织的DNA,用聚合酶链反应(PCR)、单链构象多态性分析(SSCP)和DNA测序等方法检测APC基因第15外显子突变密集区(mutation cluster region,MCR)区段、K-ras和p53基因的突变。结果:APC、K-ras和p53基因的突变率分别为37.5%(18/48)、43.8%(21/48)和35.4%(17/48)。48例结直肠癌组织中,有42例发生APC、K-ras或p53基因突变,突变率高达87.5%(42/48),其中仅有APC、K-ras或p53 1种基因发生突变的发生率分别为16.7%(8/48)、25.0%(12/48)和20.8%(10/48)。单独1种基因发生突变的总发生率为62.5%(30/48)。APC和p53,APC和K-ras或p53和K-ras 2种基因均有突变的发生率分别为6.3%(3/48)、10.4%(5/48)和4.2%(2/48)。APC、K-ras和p53 3种基因均发生突变的发生率为4.2%(2/48)。2种和3种基因均发生突变的总发生率为25%(12/48)。结论:结直肠癌的发生、发展并不完全遵循由正常结直肠黏膜上皮细胞向腺瘤和侵袭性癌转化的过程中,及依次发生“APC→K-ras→p53→DCC”突变累积这一经典的结直肠癌发生发展模式,可能存在其他结直肠癌发病机制。

癌性胸腔积液K-ras基因突变检测及临床应用

目的：探讨Ｋ－ｒａｓ 基因突变检测用于癌性胸腔积液的诊断价值。方法：采用ＰＣＲ－ ＳＳＣＰ技术对５８ 例癌性及３０ 例结核性胸腔积液进行Ｋ－ｒａｓ 基因突变分析。结果：结核性胸液未发现突变，癌性胸液有１７ 例突变阳性，突变率２９－３ ％ ，其中腺癌所致胸腔积液突变率为３４－１％ （１４／２１），鳞癌１６－７ ％（２／１２）。１７ 例Ｋ－ｒａｓ 基因突变阳性的胸液中，１４ 例为肉眼血性，明显高于非血性胸液组，Ｐ＜ ０－０５。１８ 例未找到原发病灶的胸液中４４－４％ Ｋ－ ｒａｓ 基因突变阳性。４９ 例患者随访１０ 个月，Ｋ－ｒａｓ 基因突变阳性者死亡率高达８０－０ ％ ，而无Ｋ－ｒａｓ 基因突变者死亡率明显降低，为２６－５ ％ ，Ｐ＜ ０－０５ 。结论：Ｋ－ｒａｓ 基因突变检测是诊断癌性胸腔积液的又一有效手段，在某些情况下显示出特有的优势，并且对预后的判断有一定价值。

非小细胞肺癌中EGFR和K-ras基因突变与蛋白表达相关性的研究

背景与目的:当前表皮生长因子受体(epidermal growth factor receptor,EGFR)基因靶向治疗已成为晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)治疗的研究的热点之一。本研究旨在探讨NSCLC患者中EGFR基因和K-ras(Kirsten rat sarcoma viral oncogene)基因突变的情况,分析其与蛋白表达的相关性及对吉非替尼(gefitinib)治疗的指导意义。方法:收集200例NSCLC患者新鲜组织,采用基因测序法检测EGFR及K-ras基因突变的状态;同时采用免疫组织化学法检测EGFR和K-ras蛋白的表达。结果:200例患者中,EGFR基因突变率为33%,主要发生在19号和21号外显子;K-ras基因突变率为5.5%,主要位于第12密码子;不存在同时携带有EGFR和K-ras两种基因突变的病例。腺癌尤其是含细支气管肺泡癌(bronchioloalveolar carcinoma,BAC)病理分型的患者、非吸烟患者和女性患者EGFR突变率较高。EGFR蛋白表达阳性率为16%,与总的EGFR突变无关(P>0.05),但与19号外显子突变具有统计学意义(P<0.05)。K-ras蛋白表达阳性率为52.5%,与K-ras基因突变无关(P>0.05)。15例携带有EGFR基因突变的NSCLC患者服用吉非替尼,12例(其中8例为EGFR蛋白表达阴性)有效。结论:EGFR蛋白表达与EGFR基因19号外显子突变具有一定相关性;联合检测EGFR和K-ras基因突变可用来筛选对EGFR酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)治疗敏感的人群,并预测吉非替尼治疗晚期NSCLC的疗效及预后。

XELOX和OLF化疗方案治疗K-ras基因突变型老年晚期大肠癌的疗效分析

目的比较分析K-ras基因突变型老年晚期大肠癌患者接受奥沙利铂联合卡培他滨(XELOX)和奥沙利铂联合氟尿嘧啶(OLF)化疗方案的疗效。方法分析2009年1月-2012年8月该院收治的经基因分析确诊为K-ras基因突变型晚期大肠癌病例,共106例。其中接受XELOX化疗者56例,接受OLF化疗者50例,并比较分析两组接受化疗后发生毒副反应、客观缓解率、疾病控制率、无进展生存期、总生存期的差异。结果O LF组骨髓抑制、恶心呕吐、静脉炎、心脏毒性的发生率高于XELO X组,而腹泻的发生率XELO X组要明显高于OLF组,在口腔炎及神经毒性的发生率上,两组差异无统计学意义。两组客观缓解率、疾病控制率、无进展生存期和总生存期差异无统计学意义。结论 XELOX治疗K-ras基因突变型老年晚期结肠癌具一定疗效,相对安全,可提高患者的生存质量。

粪便中检测K-ras基因突变对老年大肠癌诊断价值的研究

探讨粪便K ras基因检测在老年大肠癌临床诊断中的价值。收集连续就诊的 2 3例老年大肠癌患者、2 0例结肠腺瘤性息肉患者及 2 0名健康老年查体者的粪便 ,并从中提取DNA ,应用等位基因特异性杂交技术检测粪便K ras基因第 12位密码子第 1、2位碱基突变情况。结果K ras基因突变率在大肠癌患者为 5 6 5 2 % (13/ 2 3) ,明显高于正常查体者的 5 % (1/ 2 0 ) (P <0 0 1) ,与结肠腺瘤性息肉组的 30 % (6 / 2 0 )比较 ,差异无显著性意义 (P >0 0 5 )。 92 31% (12 / 13)的大肠癌K ras基因突变位点发生在第 12位密码子第 2位碱基。研究表明 ,结肠癌患者组织及粪便中K ras基因突变的检出具有良好的一致性 ,提示粪便中检测K

电化学发光-聚合酶链式反应方法检测胰腺癌中K-ras基因点突变

发展了一种可用于快速检测胰腺癌中K-ras癌基因点突变的电化学发光-聚合酶链式反应(ECL-PCR)分析方法。该法采用三联吡啶钌标记的上游引物和生物素标记的下游引物对目的片段进行PCR扩增;再采用限制性内切酶MvaI对扩增产物进行酶切。由于野生型样品和突变型样品间存在酶切位点的变化,其中只有野生型样品能被切断;通过生物素与链霉亲和素包被的磁珠连接,将生物素标记的DNA片段收集到检测池中,进行电化学发光检测。采用该法对13例胰腺癌组织中的K-ras癌基因第12位密码子进行点突变分析,只需要10μL样品、20min孵育时间和30s采集时间,就可得出其中有12例存在点突变,点突变率为92.3%。本方法操作简便、安全、快速、灵敏,可用于检测任何一种导致限制性内切酶位点改变的基因点突变。

非小细胞肺癌中EGFR和K-ras基因突变检测分析与病理特征的关系

目的探讨不同分型非小细胞肺癌的EGFR与K-ras基因突变及其相关病理特征的关系。方法基因测序方法检测260例非小细胞肺肿瘤患者肿瘤组织中的EGFR(18,19,20,21外显子)和K-ras(12,13,61密码子)基因的突变。结果 260例样本中,EGFR基因突变检出率为48.8%(127/260),突变主要集中在19号外显子的缺失和21号外显子的点突变。K-ras基因突变检出率为10%(26/260),其中12、13和61密码子均发现突变。受检的所有样本中没有发现EGFR与K-ras基因同时出现突变的情况。腺癌的EGFR突变检出率明显高于鳞状细胞癌等其他组织类型。在分化程度上,高分化与中分化癌基因突变检出率和中分化与低分化突变检出率比较差异显著(P<0.01)。EGFR突变与有无淋巴结转移无关(P>0.05)。K-ras基因突变与组织类型、患者性别、分化程度、有无淋巴结转移间无相关性。结论非小细胞肺癌EGFR基因突变检出率较高,K-ras基因突变检出率较低,且两种突变并不同时出现。EGFR基因突变与性别、肺癌组织类型、分化程度有关,存在多种突变。

肺癌K-ras基因突变的二步PCR检测及其临床应用

目的 探讨高敏感性Kras基因点突变检测方法在肺癌临床的应用价值。方法 应用二步(巢式)聚合酶链反应结合限制性片断多态性分析方法(PCRRFLP)检测临床肺癌标本Kras基因第12密码子点突变。结果 二步PCRRFLP法检测Kras点突变的敏感性较一步法提高约64倍。55例肺癌石蜡包埋标本中,Kras点突变检出率为47.3%;对另67例纤支镜标本进行基因检测,以Kras突变进行基因诊断的敏感性为70.9%,特异性为91.7%。结论 二步PCRRFLP法对临床肺癌标本Kras点突变检出率较高。

含奥沙利铂方案与FOLFIRI方案一线化疗对K-ras基因不同状态晚期大肠癌患者的疗效及预后影响比较

目的探究含奥沙利铂方案与FOLFIRI方案对Ⅳ期结直肠癌化疗疗效及预后影响的差别与K-ras基因状态的关系。方法收集2010年1月至2012年1月的118例接受含奥沙利铂方案或FOLFIRI方案化疗的Ⅳ期结直肠癌患者临床资料,统计患者的治疗有效率(ORR)、疾病控制率(DCR)、无进展生存时间(PFS)和总生存期(OS)。采用χ2检验比较各组临床因素差别和两种治疗方案的有效率及疾病控制率,采用Kaplan-Meier法比较无进展生存时间以及总生存期。结果 118例患者中,接受含奥沙利铂方案化疗的K-ras突变型患者PFS及OS较接受FOLFIRI方案化疗患者延长(P=0.048;P=0.037),ORR及DCR较接受FOLFIRI方案化疗患者无明显差别(P=0.961;P=0.931)。接受含奥沙利铂方案化疗的K-ras野生型患者ORR、DCR、PFS及OS较接受FOLFIRI方案化疗患者无明显差别(P=0.900;P=0.802;P=0.738;P=0.904)。结论采用含奥沙利铂方案一线化疗较FOLFIRI方案对K-ras突变型Ⅳ期结直肠癌患者更有优势,而对于K-ras野生型Ⅳ期结直肠癌患者,含奥沙利铂方案与FOLFIRI方案疗效及预后情况相当。

结直肠癌中K-ras基因突变的检测及其临床病理学意义

目的 K-ras基因在结直肠癌发生、发展中均有重要作用。K-ras野生型的患者对西妥昔单抗(Cetuximab,C225)敏感,而突变型者不敏感。文中探讨结直肠癌中K-ras基因突变情况及其临床病理学意义。方法从结直肠癌石蜡标本中提取基因组DNA,采用焦磷酸测序(pyrosequencing)法检测67例结直肠癌中K-ras基因的突变情况。结果 K-ras基因突变率为38.8%(26/67),发现6种突变类型,即第12密码子(GGT→GAT、GGT→GTT、GGT→TGT、GGT→AGT、GGT→GCT)突变和第13密码子(GGC→GAC)突变。K-ras基因突变57.7%发生在第12密码子的第2位碱基,最多见突变类型为(GGT→GAT)。女性患者K-ras基因突变率(57.7%)高于男性患者(26.8%),差异有统计学意义(P<0.05)。有淋巴结转移组K-ras基因突变率(58.8%)高于无淋巴结转移组(32.0%),差异有统计学意义(P<0.05)。K-ras基因突变与患者年龄、肿瘤位置、浸润深度、组织学类型及Dukes'分期无显著相关性(P>0.05)。结论焦磷酸测序可用于K-ras基因突变的快速检测;K-ras基因突变在女性结直肠癌患者及有淋巴结转移的患者中多见,可望成为判断结直肠癌预后的重要指标。

粪、血APC及K-ras基因突变联合检测在大肠癌筛查中的作用

目的通过联合检测粪、血浆中APC和K-ras两种基因的突变,探讨其在大肠癌筛查中的作用。方法收集本院2003年10月～2004年3月行肠镜检查患者的肝素抗凝血5ml,大便3～5g。提取粪便及血浆DNA,采用PCR-SSCP法检测APC和K-ras突变。结果和结论(1)大肠癌和腺瘤患者血浆APC基因突变分别为41.9%和57.7%(P>0.05),高于正常对照组(P<0.05)。粪便APC基因突变分别为51.6%和42.3%(P>0.05),高于正常对照组(P<0.05)。两种检测方法具有高度的吻合度(kappa值为0.811,P<0.001)。(2)血浆K-ras基因突变在大肠癌、腺瘤和正常对照分别为48.4%、3.8%和0%,粪便K-ras基因突变在3组中分别为54.8%、7.7%和11.1%,大肠癌组高于腺瘤组和正常组(P<0.05),腺瘤组和正常组间无差异(P>0.05)。两种方法检测的吻合度一般(kappa值为0.662,P=0.000)。(3)联合检测APC及K-ras基因突变可以提高诊断大肠癌的灵敏度。血、粪联合检测检测APC和K-ras基因突变较粪便检测无明显优势。(4)APC基因突变与是否发生肿瘤区域淋巴结转移有关,K-ras基因突变与病变分化程度有关。

应用肽核酸钳制PCR技术检测胰腺癌K-ras基因突变

目的:应用肽核酸钳制PCR技术检测胰腺癌K-ras基因突变,探讨其诊断价值。方法:结合特异性肽核酸(针对野生型序列)与实时定量PCR技术建立一步K-ras基因检测法,与传统限制性片段长度多态性PCR法检测结果进行比较,评价新方法的诊断价值。结果:肽核酸钳制PCR法可同时对胰腺癌标本中K-ras基因的第12、13密码子突变情况进行检测,操作简便;可在105倍的野生型K-ras基因背景下检测出突变,灵敏度为0.001%,可检测突变基因最低限为102拷贝;该方法可同时进行较大规模的样品检测,单次检测时间仅需1h。而传统方法可检测的突变基因最低限为103拷贝,检测灵敏度为0.01%;需花费约2d完成同样数量的样本检测。结论:肽核酸钳制实时定量PCR法较限制性片段长度多态性PCR法有明显优势,适用于胰腺癌大规模临床样本的K-ras基因突变检测,可作为胰腺癌筛查的有效手段。

胃粘膜肠化生组织中p53、APC、K-ras基因突变的研究

目的:探讨p53、APC及K-ras基因突变在不同类型肠化生癌变中的作用。方法:用PCR-SSCP及PCR-RFLP技术检测了47例肠化生组织中p53基因5-8外显子及APC基因15-6外星子、K-ras基因第12位点突变。结果:47例杨化生组织中p53突变14例，占29.8％，APC及K-ras基因突变各3例，分别占68％。场化生中Ⅰ、Ⅱ型肺化33例，Ⅲ型肠化14例（其中3例与Ⅱ型历化并存），Ⅲ型历化中p53突变率为57.1％（8／14），显著高于Ⅰ、Ⅱ型场化（18.2％，6／33，P＜0.05），而APC，K-ras基因在Ⅲ型肠化中的突变率（均为14.3％）虽也高于Ⅰ、Ⅱ型肠化（均为3.0％），但统计学检验无显著意义（P＞0.05）。1例Ⅲ型场化同时检出p53及K-ras突变.结论:不同类型历化生共分子改变机制有所不同，p53基因与Ⅲ型场化生的发生及癌变可能密切相关，并可能成为胃癌早期诊断的分子标志。