hMLH1基因高甲基化在胃癌发生、发展中的作用

基因启动子区CpG岛甲基化使许多基因失活，从而导致恶性肿瘤的发生和发展。目的：检测hMLHl基因启动子区CpG岛甲基化水平，探讨其胃癌发生、发展中的作用。方法：以甲基化特异性聚合酶链反应（MSP）检测41例胃癌、40例癌前病变和38例对照组织中hMLHl基因启动子区CpG岛甲基化状态，并分析其与胃癌患者临床病理特征的关系。结果：胃癌组织中hMLHl基因启动子区CpG岛甲基化阳性率为34．1％，显著高于癌前病变组的5．0％和对照组的0％（P〈0．05）。hMLHl基因甲基化阳性率与胃癌患者的年龄和肿瘤浸润深度有关（阳性率分别为46．4％对7．7％和55．0％对14.3％，P〈0．05），与性别、肿瘤分化程度和淋巴结转移无关（阳性率分别为34．8％对33．3％、28．0％对43．8％和38．1％对30．0％）。结论：胃癌组织中存在hMLHl基因启动子区CpG岛高甲基化，可能与胃癌的发生、发展有关．且可能在老年胃癌患者的肿瘤发生过程中起重要作用。     

肝细胞肝癌谷胱甘肽硫转移酶P1甲基化研究

目的本研究探讨谷胱甘肽硫转移酶（GST）PI启动子CpG岛甲基化与肝细胞肝癌（HCC）的关系。方法用甲基化特异性PCR技术检测53例HCC肿瘤组织及其癌旁非肿瘤组织中，GSTP1基因启动子CpG岛甲基化状况。结果GSTP1基因在HCC肿瘤组织中的甲基化率显著高于癌旁非肿瘤组织（X^2=19．08，P〈0．001），在Ⅲ-Ⅳ期肿瘤中的甲基化率显著高于Ⅰ-Ⅱ期肿瘤（X^2=4．84，P=0．028），在不同大小的肿瘤之间、单个结节与多个结节的肿瘤之间以及包膜完整的肿瘤与包膜不完整的肿瘤之间甲基化率的差异均无显著性。结论GSTP1启动子CDG岛甲基化可能参与肝细胞的痛性转变。     

不同阶段结直肠肿瘤分泌型卷曲相关蛋白基因甲基化及表达

目的探讨分泌型卷曲相关蛋白（sFRP）家族基因启动子CpG岛甲基化在结直肠肿瘤发生、发展和诊断中的作用。方法分别用甲基特异性PCR和逆转录PCR检测72例结直肠腺癌、33例腺瘤、18个变性隐窝灶（ACF）中sFRP基因甲基化及mRNA表达。结果正常大肠黏膜不存在sFRP基因甲基化。sFRP1、2、4、5甲基化率在腺癌中分别为93。1％、83。3％、36．1％和52．8％；在腺瘤中分别为87．9％、81．8％、24．2％和57．6％；ACF中分别为94．4％、77．8％、27．8％和55．6％。腺癌、腺瘤和ACF间sFRP基因甲基化率差异无统计学意义（P〉0．05），肿瘤组织甲基化率均高于正常黏膜及癌旁正常组织（P〈0．05）。正常黏膜表达sFRPl～5基因mRNA。与正常黏膜相比，腺癌中sFRP1、2、4、5分别在90．3％、70．8％、26．4％和61．1％的样本中表达下调（P〈0．05）；腺瘤中sFRP1、2、5分别在75．8％、45。5％和39。4％的样本中表达下调（P〈0．01）。腺癌中sFRP2、4、5表达下调较腺瘤更常见（P〈0．05）。sFRP3基因启动子不含CpG岛，仅极少数肿瘤标本（7／105）表达下调。肿瘤组织中sFRP基因表达下调与基因启动子高甲基化相关（P〈0．05）。结论sFRP基因家族在ACF中已出现高频率甲基化，是结直肠肿瘤发生常见的早期事件，可能导致sFRP基因表达下调。sFRP1、2、5甲基化可能成为早期发现结直肠肿瘤的生物学标记。     

胃腺癌凝血栓蛋白1基因异常甲基化及其临床意义

目的　探讨凝血栓蛋白 1(THBS1)基因CpG岛异常甲基化与胃腺癌 (GAC)发生的关联。方法　应用甲基化特异性PCR检测技术 ,检测 82例GAC患者肿瘤组织 ,30例十二指肠球部溃疡 (对照组 )、30例慢性胃炎伴肠上皮化生或异型增生患者胃窦黏膜组织中 ,THBS1基因启动子CpG岛甲基化分布情况。结果　THBS1基因启动子CpG岛甲基化在对照组 (6 .7% )中的频率明显低于胃炎组(2 6 .7% ,χ2 =4 .32 ,P =0 .0 38)和胃癌组 (4 7.6 % ,χ2 =16 .2 ,P <0 .0 0 1) ,在胃炎组与胃癌组之间的频率差异也有显著性 (χ2 =4 .14 ,P =0 .0 4 2 ) ,老年胃癌患者 (6 3.6 % )中的频率明显高于非老年 (36 .7% ,χ2 =5 .72 ,P =0 .0 17) ,在TNMⅢ和Ⅳ期肿瘤 (6 6 .7% )组织中的频率明显高于Ⅰ期 (36 .8% )或Ⅱ期(36 .4 % ,χ2 =6 .93,v =2 ,P =0 .0 31) ,而肿瘤部位之间、Lauren分型肿瘤之间及不同分化程度肿瘤之间 ,THBS1基因甲基化率的差异无显著性。结论　THBS1基因启动子CpG岛甲基化可能与胃腺癌的发生有关 ,且以老年患者及Ⅲ和Ⅳ期肿瘤多见。     

甲状腺乳头状癌组织中TSHR基因启动子甲基化研究

目的探讨甲状腺乳头状癌组织中促甲状腺激素受体基因（Thyroid Stimulating Hormone Receptor,TSHR）基因启动子区5端CpG岛甲基化改变的特点与临床特征的关系。方法采用甲基化特异性PCR（MSP,methylation-specific PCR）方法检测TSHR基因启动子甲基化情况。结果（1）22／34例甲状腺乳头状癌组织中检测到TSHR基因启动子甲基化,9／34例甲状腺乳头状癌癌旁组织中检测到TSHR基因启动子甲基化,癌组织中TSHR基因启动子甲基化率显著增高（χ^2=10．019,P=0．002〈0．05）;（2）有淋巴结转移的甲状腺乳头状癌组织（15／18例）TSHR基因启动子的甲基化显著高于无淋巴结转移组（7／16例）（χ^2=5．812,P=0．016〈0．05）。结论TSHR基因启动子异常甲基化是甲状腺乳头状癌发展过程中的分子事件之一,可能影响了甲状腺乳头状癌细胞的摄碘的功能。     

胃癌RASSF1A基因启动子CpG岛甲基化与DNMT1表达的意义

目的探讨RAS相关区域家族1A（RASSF1A）基因启动子CpG岛甲基化和DNA甲基转移酶1（DN-MT1）的表达与胃癌发生的关系。方法运用甲基化特异性聚合酶链反应和免疫组织化学方法检测胃癌癌旁正常组织和癌组织RASSF1A基因启动子CpG岛甲基化发生率及DNMT1的表达情况。结果癌旁正常组织中RASSF1A基因启动子CpG岛甲基化发生率、DNMT1阳性表达率显著低于相应癌组织（P均〈0.01）。RASSF1A启动子CpG岛甲基化患者DNMT1阳性表达率与非甲基化患者比较无统计学差异（P〉0.05）。结论RASSF1A基因启动子区CpG岛甲基化和DNMT1的高表达可能与胃癌发生有一定关系。     

胃癌组织中E—cadherin基因启动子异常甲基化状态观察

目的观察胃癌组织中E—cadherin基因启动子异常甲基化状态。方法采用甲基化特异性聚合酶链反应（MSP）技术检测54例胃癌及其癌旁正常组织中的E—cadherin基因启动子异常甲基化状态,并分析E-cadherin基因启动子异常甲基化状态与胃癌临床病理参数的关系。结果胃癌组织中的E-cadherin基因启动子异常甲基化发生频率为48．10％（26／54）,明显高于癌旁正常组织中的11．11％（6／54）。E—cadherin基因启动子异常甲基化频率与胃癌分化程度、病理类型、浸润深度以及淋巴结转移、临床分期有关（P均〈0．05）。结论胃癌组织中E-cadherin基因启动子异常甲基化频率较高,并与胃癌浸润、转移有关。     

BRCA1基因启动子异常甲基化与散发性乳腺癌的关系

目的 探讨散发性乳腺癌BRCA1基因启动子异常甲基化状况及其与散发性乳腺癌关系。方法 用甲基化特异PCR（MSP）法对散发性乳腺癌病人癌组织、癌旁组织及乳腺纤维腺瘤组织进行BRCAl异常甲基化检测。结果 在58例散发性乳腺癌中有17例癌组织检出了BRCAl基因启动子异常甲基化，甲基化频率为29．3％（17／58），相应的癌旁组织及乳腺纤维腺瘤组织均只检出未甲基化的BRCAl。在组织分型中，浸润性导管癌与浸润性小叶癌无显著差异（P〉0．05），二者各自与髓样癌＋黏液腺癌有显著差异（P〈0．05）。有淋巴结转移的BRCA1基因启动子甲基化率高于无淋巴结转移组（P〈0．005）。BRCA1甲基化与散发性乳腺癌的肿瘤分级及病人绝经与否均无显著差异（P〉0．05）。结论 在散发性乳腺癌中，BRCA1基因启动子具有很高的甲基化率，并与散发性乳腺癌的组织分型、恶性转移等方面有一定的关系。     

散发性乳腺癌组织中EMSY基因启动子甲基化状态观察

目的观察散发性乳腺癌组织中EMSY基因启动子CpG岛甲基化的状态。方法用特异性甲基化PCR法检测66例散发性乳腺癌和32例正常乳腺组织中EMSY基因启动子区甲基化情况。结果乳腺癌组织有11例（16．7％）、正常乳腺组织有12例（37．5％）EMSY基因启动子发生甲基化,两者相比,P〈0．05。结论散发性乳腺癌组织中EMSY基因启动子区呈低甲基化状态,可能与散发性乳腺癌的发生发展有关。     

NF-kB、Ki-67和E—cad在皮肤鳞状细胞癌和基底细胞癌的表达及相关分析

目的观察NF．KB、Ki-67和E—cad在皮肤基底细胞癌（BCC）和鳞状细胞癌（SCC）的表达,并探讨其意义。方法采用免疫组化EnVision二步法检测30例皮肤BCC和50例皮肤SCC（其中Ⅰ级26例,Ⅱ～Ⅲ级24例）中的NF—KB、Ki-67和E—cad表达,并以20份正常皮肤组织作为对照组。结果NF—KB、Ki-67在皮肤BCC和SCC的阳性表达率显著高于对照组,且在皮肤SCC的阳性表达率显著高于BCC（P〈0．05）。SCCⅡ-Ⅲ级强阳性率（＋＋-＋＋＋）显著高于SCCI级（P〈0．05）。E—cad在正常皮肤中呈阳性表达,但在肿瘤组织中的表达下降,尤以SCC下降明显,其中在SCCⅡ～Ⅲ级中的表达较SCCI级下降明显（P〈0．05）。皮肤BCC和SCC组织中NF—KB和Ki-67的阳性细胞表达呈正相关（P〈0．05）,NF．KB和E—cad的表达呈负相关（P〈0．05）。结论随着肿瘤细胞分化程度的降低,NF．KB、Ki-67的表达有增高趋势,E．cad的表达有下降趋势。提示BCC和SCC侵袭性生长与NF—KB、Ki-67的表达增高有关,SCC易发生转移的特性与E—cad的低表达有关。NF—KB信号转导通路有可能通过对凋亡基因的控制来对Ki-67、E—cad进行调节,进而控制肿瘤。     

Choroidal and cutaneous metastasis from gastric adenocarcinoma

Choroidal or cutaneous metastasis of gastric cancer is rare. Gastrointestinal cancer was found in only 4% in patients with uveal metastasis. Choroidal metastasis from gastric cancer was reported in two cases in earlier literature. The frequency of gastric cancer as a primary lesion was 6% in cutaneous metastasis of men, and cutaneous metastasis occurs in 0.8% of all gastric cancers. We report a patient with gastric adenocarcinoma who presented with visual disorder in his left eye and skin pain on his head as his initial symptoms. These symptoms were diagnosed to be caused by choroidal and cutaneous metastasis of gastric adenocarcinoma. Two cycles of chemotherapy consisted of oral S-1 and intravenous cisplatin (SPIRITS regimen); this was markedly effective to reduce the primary gastric lesion and almost all the metastatic lesions.     

30例老年人细支气管肺泡癌的诊断与治疗

目的探讨老年人细支气管肺泡癌（ｂｒｏｎｃｈｏａｌｖｅｏｌａｒｃａｒｃｉｎｏｍａ，ＢＡＣ）的临床特点，以期提高诊治水平。方法对３０例经病理证实的老年人ＢＡＣ进行了分析。结果其主要临床症状与其之肺部疾病相似。２９例的Ｘ线表现：孤立结节型１７例，弥漫型１１例，空洞型１例。手术、痰细胞学检查、经纤维支气管镜肺活检、支气管肺泡灌洗液细胞学检查有助于ＢＡＣ的确诊。手术切除率为７０％，其中Ⅰ期和Ⅱ期患者为１００％，无因手术造成死亡者，双肺弥漫型患者预后差。结论对于老年人ＢＡＣ的手术治疗，特别是孤立结节型，应持积极态度。     

148例日本老年人口腔颌面部恶性肿瘤临床分析

目的：探讨老年人口腔颌面部恶性肿瘤的发病、治疗和预后,为临床诊治提供依据。方法：对日本九州大学齿学部第二口腔外科1987年1月至1995年12月住院治疗的老年口腔颌面部恶性肿瘤患者进行回顾性分析。结果：老年口腔颌面部恶性肿瘤患者共148例,男性77例,女性71例;年龄60－94岁,平均72．2岁。入院时发生频率最高的并存症是高血压43例,占29．1％;无任何全身并存症的患者仅占12．8％。148例恶性肿瘤中,鳞状上皮癌132例,占89．2％。其发病部位顺序为牙龈51例（34．5％）、舌32例（21．6％）、口底部24例（16．2％）、颊部17例（11．5％）、腭部10例（6．8％）。46例Stage Ⅳ期患者中,肿瘤部位有义齿者35例,占76．1％。发现重复癌10例（6．8％）,男女比为1．5：1。3年累计生存率78．2％,5年累计生存率64．6％。行放射疗法＋化学疗法＋手术的综合疗法治疗者68例,5年生存率为75．5％。结论：老年患者近90％患有全身并存症;不良义齿、金属充填物等长期局部刺激与口腔癌的发病有一定的关系;老年人重复癌发病率逐年升高,应进行长期追踪观察;综合疗法疗效较好。     

Synchronous pancreatic solid pseudopapillary neoplasm and intraductal papillary mucinous neoplasm

Solid pseudopapillary neoplasm (SPN) is a rare and low-grade malignant pancreatic neoplasm composed of poorly cohesive monomorphic neoplastic cells forming solid and pseudopapillary structures with frequent hemorrhagic-cystic degeneration. Intraductal papillary mucinous neoplasm (IPMN) is a pancreatic exocrine tumor composed of intraductal papillary growth of mucin containing neoplastic cells in the main pancreatic duct or its major branches. In the case presented here, a 53-year-old, Japanese man was found to have multiple cystic lesions and dilatation of the main pancreatic duct in the neck of the pancreas. Histological examination revealed a main-duct and branch-duct type IPMN, of the gastric-type, involving the neck of the pancreas, associated with a 0.5 cm SPN in the caudal side of the IPMN. We diagnosed this case as synchronous SPN and IPMN. As far as we know, only one other case of synchronous SPN and IPMN has been reported. Both the present case and the previously reported case showed abnormal nuclear expression of β-catenin in SPN, whereas IPMN showed no abnormal nuclear expression. These results suggest that β-catenin abnormality is not a common pathogenetic factor of synchronous SPN and IPMN.     

老年人多原发恶性肿瘤57例分析

目的总结老年人原发恶性肿瘤的临床和病理特点。方法统计本院２４年间经病理确诊的老年人多原发恶性肿瘤５７例，从检出率、发病年龄、发病部位、间隔时间、死亡原因、肿瘤组合等方面加以分析。结果５７例中，２癌４５例，３癌１０例，４场２例；死亡４３例，尸检率８８．４％；发病（或发现）年龄６０～８０岁３７例（６４．９％）；发病部位前４位依次为：肺、结肠、前列腺、胃；发生于同一或成对器官的肿瘤１６例；同时性肿瘤１５例，异时性４２例；平均肿瘤发生间隔时间７年４个月。结论（１）尸检率较高的老年人群中，多原发恶性肿瘤发生率高；（２）肺、结肠、前列腺、胃及同一或成对器官易发生多原发恶性肿瘤；（３）尽早手术在老年人多原发恶性肿瘤中不失为良策。     

Associations between serum uric acid and hepatobiliary-pancreatic cancer: A cohort study

BACKGROUNDUric acid is the end product of purine metabolism. Previous studies have found that serum uric acid (SUA) levels are associated with the total cancer risk. However, due to the dual effect of uric acid on cancer, the relationship between the SUA levels and most specific-site cancer remains unclear.AIMTo investigate the associations between the SUA levels and incidence of hepatobiliary-pancreatic cancer.METHODSIn this prospective cohort study, 444462 participants free of cancer from the UK Biobank were included. The SUA levels were measured at baseline, and the incidence of hepatobiliary-pancreatic cancer was determined by contacting the cancer registry. The hazard ratios (HRs) and 95% confidence intervals (CIs) between the SUA levels and hepatobiliary-pancreatic cancer were investigated using multiple adjusted Cox regression models adjusted for potential confounders.RESULTSIn total, 920 participants developed liver, gallbladder, biliary tract or pancreatic cancer during a median of 6.6 yrs of follow-up. We found that the HR of pancreatic cancer in the highest SUA group was 1.77 (95%CI: 1.29-2.42) compared with that in the lowest group. After stratifying by gender, we further found that SUA was associated with an increased risk of pancreatic cancer only among the females (highest quartile vs lowest quartile HR 2.04, 95%CI: 1.35-3.08). Among the males, the SUA levels were positively associated with the gallbladder cancer risk (highest quartile vs lowest quartile HR 3.09, 95%CI: 1.28-7.46), but a U-shaped association with the liver cancer risk was observed (P-nonlinear = 0.03).CONCLUSIONSUA is likely to have gender-specific effects on hepatobiliary-pancreatic cancer. High SUA levels are a risk factor for pancreatic cancer in females and gallbladder cancer in males. A U-shaped association with the liver cancer risk was identified.     

Two synchronous somatostatinomas of the duodenum and pancreatic head in one patient

Somatostatinomas are extremely rare neuroendocrine tumors of the gastrointestinal tract, first described in the pancreas in 1977 and in the duodenum in 1979. They may be functional and cause somatostatinoma or inhibitory syndrome, but more frequently are non-functioning pancreatic endocrine tumors that produce somatostatin alone. They are usually single, malignant, large lesions, frequently associated with metastases, and generally with poor prognosis. We present the unique case of a 57-year-old woman with two synchronous non-functioning somatostatinomas, one solid duodenal lesion and one cystic lesion within the head of the pancreas, that were successfully resected with a pylorus-preserving Whipple's procedure. No secondaries were found in the liver, or in any of the removed regional lymph nodes. The patient had an uneventful recovery, and remains well and symptom-free at 18 mo postoperatively. This is an extremely rare case of a patient with two synchronous somatostatinomas of the duodenum and the pancreas. The condition is discussed with reference to the literature.     

循环 microRNAs 在肝胆胰肿瘤发生发展中的作用

微小 RNA（miRNAs）参与机体的生长发育及疾病的病理生理过程,尤其在肿瘤性疾病的发生发展过程中起到致瘤基因或抑瘤基因的作用,另外全身血液循环中存在与特定肿瘤组织相应的循环 miRNAs。总结了近年来国内外研究发现的与肝胆胰肿瘤相关的循环 miRNAs,并分别阐述了 miRNAs 在肝胆胰肿瘤的诊断、临床病理分型、治疗及预后方面的应用价值。提出循环 miRNAs有望成为临床肿瘤筛查、诊断、治疗以及预后评价的新的生物标志物。     

A case of synchronous squamous cell carcinoma in the esophagus and stomach

Synchronous esophageal and gastric cancers with the pathologic features of a squamous cell carcinoma are extremely rare. A 57-year-old male visited our hospital with a history of hematemesis and was diagnosed with a synchronous cancer. He underwent a staging work-up, and the resectable lesion in the stomach was operated on following radiologic and endoscopic evaluations. The pathologic examination revealed a synchronous cancer consisting of squamous cell carcinoma in the distal esophagus and the cardia of the stomach. We report a case of a synchronous cancer that was successfully treated by surgical resection followed by concurrent chemoradiotherapy. We also discuss the hypothesis regarding the origin and presentation of the synchronous cancer and highlight the importance of careful surveillance by physicians at the time of diagnosis.     

胃肠神经内分泌肿瘤和胰腺神经内分泌肿瘤的区别

胃肠胰神经内分泌肿瘤（GEP-NETs）主要来源于胃肠胰系统的神经内分泌细胞,这一细胞系统和肿瘤是以表达细胞类型特异的肽激素和普通标记物（突触囊泡蛋白、铬粒素A）为特征。其特点为：临床上少见;肿瘤通常较小（〈1 cm）;生长速度较慢（数月或数年）,呈阶段性表达,可能数年无症状;通常在出现症状前即有转移,转移部位多为肝脏和骨,而此时肿瘤的体积通常〉2cm。因此这类肿瘤经常被误诊,诊断过程较复杂,不单单依靠临床,往往需要高端的实验室和扫描手段支持。而GEP-NETs中胃肠神经内分泌肿瘤（NET）和胰腺NET,两者在临床表现、诊断和治疗方面也有不同,需要临床医生重视和加以区分。