DAPK蛋白、Ki-67蛋白在子宫内膜癌中的表达及其与临床病理学特征的相关性

目的:探讨DAPK蛋白、Ki-67蛋白在子宫内膜癌中的表达及其与临床病理学特征的相关性。方法:选取2012年6月至2016年10月在我院及邯郸市第一医院治疗的子宫内膜癌患者150例,同时选取150例子宫内膜增生患者,采用免疫组化法检测DAPK蛋白、Ki-67蛋白表达情况,采用全自动生化法检测血清中CEA、CA19-9和CA125等的表达,分析 DAPK蛋白、Ki-67蛋白的表达与子宫内膜癌临床病理特征的关系。结果:子宫内膜癌患者组织中的DAPK蛋白低于子宫内膜增生组（P＜0.05）,Ki-67蛋白阳性表达率均高于子宫内膜增生组患者（P＜0.05）;子宫内膜癌组患者CEA、CA19-9和CA125水平均高于子宫内膜增生组（P＜0.05）;子宫内膜癌患者的DAPK阳性表达率与CEA等肿瘤标志物水平负相关（P＜0.05）,子宫内膜癌患者的Ki-67阳性表达率与CEA等肿瘤标志物水平正相关（P＜0.05）;不同年龄的患者间DAPK、Ki-67的表达无差异,高分化、无淋巴结转移、TNM分期为Ⅰ+Ⅱ期的子宫内膜癌患者的DAPK阳性表达率较高（P＜0.05）,高分化、无淋巴结转移、TNM分期为Ⅰ+Ⅱ期的子宫内膜癌患者的Ki-67阳性表达率较低（P＜0.05）。结论:DAPK蛋白、Ki-67蛋白在子宫内膜癌患者中存在异常表达,且其表达与患者的病情或者细胞分化、淋巴结转移等具有密切关系。     

错配修复蛋白在左、右半结肠癌组织中的表达差异及其临床意义

目的:探讨错配修复（mismatch repair,MMR）蛋白在左半结肠癌（left colon cancer,LCC）和右半结肠癌（right colon cancer,RCC）组织中的表达及其临床意义。方法:收集2014年01月至2017年12月间在我院接受手术治疗的368例结肠癌患者的临床病理资料，根据肿瘤原发部位分为LCC组与RCC组，分析MMR蛋白在LCC、RCC组织中的表达是否存在显著差异，同时探讨LCC、RCC的临床病理特征，并分析MMR蛋白对LCC、RCC预后的指导意义。结果:368例结肠癌组织中dMMR为25.8%。单因素分析结果显示，在不同肿瘤部位MMR蛋白的表达有显著性差异（P＜0.05），RCC组中dMMR为17.4%，明显高于LCC组的8.4%；另外LCC、RCC在肿瘤直径、分化程度、组织学类型上存在统计学差异（均P＜0.05）。进一步Logistic多因素分析发现:肿瘤直径≥5 cm（OR=1.762,95%CI:1.144～2.713，P=0.010）、dMMR（OR=2.672,95%CI:1.617～4.417，P=0.000）均为RCC的独立相关因素。Kaplan-Meier生存分析显示，dMMR组患者的OS显著高于pMMR组患者（P=0.035）；经肿瘤部位分层分析发现，RCC组中dMMR患者的OS显著高于pMMR患者（P=0.004），但在LCC组中dMMR患者与pMMR患者的OS无显著性差异（P=0.951）。结论:RCC中dMMR发生率明显高于LCC，且仅在RCC中提示着较好的预后作用，而在LCC中无预后指示作用。     

结直肠癌组织中DDX5表达水平及其与患者预后的相关性

目的:探讨RNA解螺旋酶DDX5(p68)在结直肠癌（colorectal cancer,CRC）组织中的表达水平及其与结直肠癌患者预后的相关性。方法:选取2015年03月至2016年11月陆军军医大学第二附属医院收治的接受外科手术初治的213例结直肠癌患者,收集其临床资料、肿瘤组织石蜡标本;采用免疫组化方法检测肿瘤组织中DDX5蛋白表达情况;随访3年,分析DDX5蛋白表达水平与结直肠癌患者预后的关系。结果:截止2019年11月30日,共有202例患者完成随访;死亡23例,复发44例,共计67例,预后不良率为33.17%;预后不良组在肿瘤分化程度上低于预后良好组,淋巴结转移情况、肿瘤浸润型比例、临床分期上高于预后良好组,差异具有统计学意义（P＜0.05）;预后不良组肿瘤组织中DDX5蛋白表达水平高于预后良好组,差异具有统计学意义（P＜0.05）;以DDX5表达水平中位数为截点,DDX5高表达组3年无进展生存率为58.88%,低于DDX5低表达组的78.30%,DDX5高表达组疾病进展风险显著高于DDX5低表达组（P=0.002）;多因素Logistic分析显示,肿瘤低分化（OR=14.097）、淋巴结N1-2转移（OR=118.602）、高临床分期（OR=1 525.596）、浸润型生长（OR=2.533）及DDX5高表达（OR=8.958）是影响结直肠癌患者预后不良的独立危险因素（P＜0.05）。结论:结直肠癌组织中DDX5蛋白高表达可导致患者预后不良,可能是评估结直肠癌预后的一项生物标志物。     

肌动蛋白凝胶蛋白和肌动蛋白凝胶蛋白2在结直肠癌组织中的表达及 其临床意义

目的:探讨结直肠癌组织中肌动蛋白凝胶蛋白（transgelin,TAGLN）及肌动蛋白凝胶蛋白2（transgelin2,TAGLN2）的表达及其临床意义。方法:选取2012年至2013年在郑州大学附属肿瘤医院接受结直肠癌根治术治疗的89例结直肠癌患者病理组织标本及配对癌旁组织,采用免疫组织化学检测TAGLN和TAGLN2在结直肠癌组织中的表达情况,结合临床资料分析TAGLN、TAGLN2与结直肠癌患者临床病理特征及预后的关系。结果:TAGLN在结直肠癌组织中的阳性表达率为60.7%（54/89）,明显高于癌旁组织38.2%（34/89）,差异有统计学意义（P＜0.05）,TAGLN表达与结直肠癌患者的TNM分期、肿瘤分化程度、Ki67表达、淋巴结转移及远处转移明显相关（P均＜0.05）;TAGLN2在结直肠癌组织中的阳性表达率为69.7%（62/89）,明显高于癌旁组织31.5%（28/89）,差异有统计学意义（P＜0.01）,TAGLN2表达与结直肠癌患者的肿瘤分化程度、Ki67表达及远处转移显著相关（P均＜0.05）。相关分析显示, TAGLN蛋白表达与TAGLN2蛋白表达呈正相关（r=0.219,P=0.039）。Kaplan-Meier生存分析显示,患者生存时间与肿瘤分化程度、TNM分期、Ki67表达、远处转移、TAGLN和TAGLN2有关,差异有统计学意义（P均＜0.05）;多因素Cox回归结果显示,远处转移、TNM分期和TAGLN是影响结直肠癌患者预后的独立危险因素（P均＜0.05）。结论:对于结直肠癌患者,TAGLN的表达与TNM分期、肿瘤分化程度、Ki67表达、淋巴结转移和远处转移有关,TAGLN2的表达与肿瘤分化程度、Ki67表达和远处转移有关。TAGLN表达、TNM分期和远处转移为结直肠癌患者预后的独立影响因素。     

Survivin在结直肠癌组织中表达的病理学意义

目的研究凋亡抑制蛋白Survivin在结直肠癌组织中表达的病理学意义.方法采用免疫织织化学染色方法(SP法)检测106例结直肠癌组织中Survivin的表达,分析Survivin表达与各病理因素及Ki-67增殖指数的关系.结果Survivin在结直肠癌组织中的表达率为64.2%(68/106例),正常的结直肠粘膜未见Survivin表达;Survivin在中高分化结直肠癌组织中表达率(72.4%)明显高于低分化结直肠癌(26.3%),(P＜0.05).此外,Survivin表达与病人性别、肿瘤位置、浸润深度、淋巴结转移、远处转移以及Dukes'分期无显著相关(P＞0.05).Survivin阳性表达结直肠癌的Ki-67增殖指数(41.31%±19.83%)明显高于Survivin阴性表达者(26.21%±20.36%),差异有显著性意义(P＜0.05).结论凋亡抑制蛋白Survivin在结直肠癌组织中存在高表达,与结直肠癌细胞分化有关,可促进结直肠癌细胞的增殖.     

错配修复基因蛋白在结直肠癌诊治中的临床应用

  目的  探讨错配修复基因（mismatch repair gene,MMR）蛋白MLH1、MSH2、MSH6、PMS2在结直肠癌中的表达及在临床中的应用。  方法  选取四川省人民医院2015年1月至2016年9月收治的607例结直肠癌患者,采用免疫组织化学法检测手术标本中MMR蛋白的表达情况,研究其与临床病理学的关系,并评价其在Lynch综合征和散发性结直肠癌筛查中的价值。  结果  607例患者中MMR表达缺失率为35.58%。MMR蛋白表达缺失的阴性组与表达正常的阳性组,在年龄、性别、肿瘤大小、P53、CD34、D2-40的比较,差异均无统计学意义（P>0.05）;两组患者在肿瘤位置、分化程度、TNM分期、淋巴结转移、VEGF、Ki-67的比较,差异均有统计学意义（P < 0.05）。联合检测MLH1、MSH2、PSM2、MSH6蛋白可以作为初步筛选Lynch综合征患者的方法。  结论  对结直肠癌患者的手术标本进行MMR检测,筛查Lynch综合征患者和家族成员,进行管理及干预,可降低部分人群患结直肠癌的风险。      

结直肠癌中 RhoGDI2的表达与肿瘤侵袭、转移及预后的关系

目的：探讨 RhoGDI2在结直肠癌中的表达与肿瘤侵袭、转移及预后的关系。方法：应用 Northern blot和 Western blot 检测具有不同侵袭、转移潜能的人结直肠癌细胞系（SW620、SW480）中 RhoGDI2 mRNA 及蛋白的表达。收集行手术切除并随访满5年的结直肠癌患者原发灶癌组织石蜡标本80例及相应的癌旁非癌组织、转移性淋巴结癌组织石蜡标本各20例。应用免疫组化法检测上述120例标本中 RhoGDI2蛋白的表达,分析其与临床病理特征及预后的关系。结果：SW620、SW480人结直肠癌细胞系中 RhoGDI2 mRNA 及蛋白的表达具有统计学差异（P <0.01）,前者表达均高于后者。结直肠癌相关组织中 RhoGDI2蛋白存在差异性表达（转移淋巴结癌组织>原发灶癌组织>癌旁非癌组织,P <0.01）。RhoGDI2蛋白在结直肠癌组织中的表达与肿瘤的浸润深度、淋巴结转移、远处转移、周围淋巴管浸润、周围神经浸润、TNM 分期显著相关（P <0.05）。RhoGDI2高表达的结直肠癌患者5年生存率显著低于低表达者（P <0.01）。高 RhoGDI2表达是结直肠癌的独立预后因素之一（P <0.05）。结论：RhoGDI2在结直肠癌中的高表达与肿瘤的侵袭、转移及预后不良密切相关,可能是一个有效的结直肠癌预后标志物。     

MMR蛋白在515例子宫内膜样腺癌中表达及其与临床病理学特征的相关性分析

背景与目的：林奇综合征（Lynch syndrome,LS）相关的子宫内膜癌有着独特的临床病理学特征及治疗手段。对新发子宫内膜癌患者采用免疫组织化学（immunohistochemistry,IHC）染色的方法检测错配修复（mismatch repair,MMR）蛋白表达情况,可以有效地筛查LS相关的癌症患者。本研究探讨MMR蛋白（MLH1、MSH2、MSH6及PMS2）在子宫内膜样腺癌中的表达情况及其与患者临床病理学特征的关系。方法：收集中国医科大学盛京医院2018年1月—2020年8月共515例子宫内膜样腺癌连续性病例为研究对象,年龄范围为28 ~ 81（57.73±8.41）岁。采用IHC染色的方法检测癌组织中MLH1、MSH2、MSH6和PMS2蛋白表达情况,应用聚合酶链式反应（polymerase chain reaction,PCR）方法对MLH1蛋白表达缺失的标本进行基因的甲基化检测,并且分析MMR蛋白表达缺失情况与子宫内膜样腺癌临床病理学特征的关系。只要有一种MMR蛋白表达缺失即判定为MMR蛋白错配修复缺陷（deficient mismatch repair,dMMR）,蛋白全部阳性则判定为MMR表达完整（proficient mismatch repair,pMMR）。结果：515例子宫内膜样腺癌中有138例（26.8%）发生MMR蛋白表达缺失,MLH1、PMS2、MSH2及MSH6蛋白表达缺失率分别是16.3%（84/515）、19.0%（98/515）、5.4%（28/515）、8.0%（41/515）。MMR蛋白的缺失以MLH1和PMS2联合表达缺失（60.9%,84/138）为主;其次为MSH2和MSH6联合表达缺失（18.8%,26/138）;MSH2、MSH6和PMS2联合表达缺失有2例（1.4%,2/138）;PMS2、MSH2和MSH6蛋白单独表达缺失比例分别为8.0%（11/138）、1.4%（2/138）、10.1%（14/138）。对27例MLH1蛋白表达缺失标本进行甲基化检测,结果显示,阳性率为85.2%（23/27）。515例子宫内膜样腺癌组织中的MMR蛋白表达缺失与患者发病年龄、国际妇产科联合会（The International Federation of Gynecology and Obstetrics,FIGO）分期、组织学分化程度、浸润深度、脉管转移、神经侵犯、淋巴结转移、p53异常表达、肿瘤浸润淋巴细胞（tumor infiltrating lymphocyte,TIL）及肿瘤伴瘤周淋巴细胞有相关性,而与是否累及子宫下段无关。与pMMR的患者相比,dMMR的患者发病年龄更小,FIGO临床分期多为Ⅲ ~ Ⅳ期,组织学分化程度多为低分化,肿瘤多无肌层浸润,肿瘤多出现脉管神经侵犯及淋巴结转移,肿瘤浸润淋巴细胞增多,且肿瘤伴瘤周淋巴细胞更显著,MSH6蛋白缺失患者多无p53异常表达。结论：dMMR的子宫内膜样腺癌患者具有独特的临床病理学特征。应用免疫组织化学染色方法检测MMR蛋白表达情况,并对MLH1表达缺失的标本进行基因甲基化检测,能初步筛查LS患者,对肿瘤患者免疫治疗具有一定指导意义。     

XRCC2在结直肠癌中的表达及其临床意义

摘 要：［目的］ 探讨XRCC2在结直肠癌组织中的表达及其临床意义。［方法］ 收集101例结直肠癌患者的标本及临床病理资料,通过qRT-PCR及免疫组化染色检测XRCC2在结直肠癌及癌旁组织中的表达,分析其与临床病理及预后之间的关系。［结果］ qRT-PCR结果表明癌组织中XRCC2 mRNA表达水平高于相对应的癌旁组织（P<0.001）;免疫组化结果显示67.3%(68/101)的结直肠癌组织XRCC2蛋白表达阳性。XRCC2蛋白表达与肿瘤大小、肿瘤T分期、M分期、TNM分期、Duke’s分期、淋巴结转移和肝脏转移有关（P<0.05）。Kaplan-Meier生存分析显示,高表达XRCC2的结直肠癌患者预后差,与XRCC2低表达的患者相比,XRCC2高表达的患者中位生存期及无复发中位生存时间明显缩短（P<0.05）。Cox回归分析显示XRCC2表达是影响结直肠癌患者预后的独立因素。［结论］ XRCC2在结直肠癌组织中呈高表达,其可能成为预测结直肠癌发生发展及预后的生物标志物。     

CEA和 CA19-9在结直肠癌组织中的表达及临床意义

目的：探讨CEA和CA19-9在结直肠癌中的表达及其与临床病理参数和预后的关系。方法采用免疫组织化学法,检测47例结直肠癌组织中CEA和CA19-9的表达,并分析两者表达与其临床病理参数和预后的关系。结果CEA和CA19-9蛋白在结直肠癌组织中呈高表达。 CEA表达与M分期显著相关,与其他临床参数无相关性。 CA19-9表达与性别、年龄、T期、N期、M期、Duke分期及肿瘤大小无相关性。 CEA和CA19-9蛋白在结直肠癌组织中的表达与其生存期无相关性,但CEA和CA19-9联合检测一定程度上可预测预后。结论 CEA表达与结直肠癌M分期显著相关, CEA和CA19-9联合检测有助于预测结直肠癌患者预后。     

错配修复基因联合中性粒细胞/淋巴细胞比值预测结肠癌术后复发的价值

目的 探讨不同错配修复基因(MMR)状态结肠癌临床病理特征,进一步评估MMR联合术前血中性粒细胞/淋巴细胞比值(NLR)用于预测结肠癌术后复发的价值.方法 回顾性分析125例结肠癌根治术后MMR免疫组织化学结果,分为错配修复缺陷组(dMMR)(55例),错配修复基因正常组(pMMR)(70例),并按MMR状态和NLR高...     

Deficient mismatch repair as a prognostic marker in stage II colon cancer patients

BackgroundA number of reports have evaluated the relationship between deficient DNA mismatch repair (dMMR) and colorectal cancer prognosis. Unfortunately, the exact prognostic role of dMMR has not been clearly established due to contradictory results. This study aims to determine the prognostic impact of dMRR in stage II colon cancer patients only. The appropriate identification of high-risk stage II colon cancers is of paramount importance in the selection of patients who may benefit from adjuvant treatment after surgery.MethodsFour hundred and fifty-two patients with curative resection of stage II colon cancer were included. Hospital records were used as data source, providing clinical, surgical, pathology, oncology and follow-up information for statistical analysis focusing on overall survival (OS) and time to progression (TTP). Mismatch repair status was determined by immunohistochemistry. Patient survival was followed-up for a mean of 77·35 months.ResultsdMMR was detected in 93 of 452 patients (20·6%). No impact on overall survival (Log-Rank, p = 0·583, 95% CI 0·76–1·67). However, the hazard ratio 0·50 for TTP was highly significant (Log-Rank, p = 0·012, 95% CI 0·28–0·87) in patients with dMMR compared with those with mismatch repair proficient tumours (pMMR).ConclusionsPatients with dMMR tumours have a lower risk for recurrence compared to those with pMMR tumours, but this finding did not correlate to better overall survival.     

胃癌患者错配修复缺陷和PIK3CA基因突变与临床病理特征的关系

目的:分析胃癌中错配修复缺陷(dMMR)和PIK3CA基因突变分别与临床病理特征的关联,以及两者之间的相关性。方法:选取本中心554例胃癌肿瘤组织标本,收集临床病理参数。免疫组化检测错配修复蛋白MSH2、MSH6、MLH1和PMS2,评判是否为dMMR。ARMS-PCR检测PIK3CA基因突变。应用统计学方法,分析dMMR和PIK3CA突变与临床病理特征的关系,以及dMMR与PIK3CA突变的关联。结果:554例胃癌患者中,dMMR 30例(5.4%)。其中,MLH1和PMS2双缺失27例(90.0%),MSH2和MSH6双缺失2例(6.7%),PMS2缺失1例（3.3%）。PIK3CA突变34例（6.1%）,其中15例E545 K (44.1%), 7例E542 K (20.1%),1例E545D(2.9%),6例H1047R(17.6%),4例H1047L(11.8%),1例E545K和E542K双突变（2.9%）。9号外显子突变24例（70.6%）,20号外显子突变10例（29.4%）。单因素分析发现,dMMR与女性,年龄> 65岁,肿瘤直径> 5 cm,肿瘤未侵及浆...     

Association between deficient mismatch repair system and efficacy to irinotecan-containing chemotherapy in metastatic colon cancer

The present study investigated the association between deficient mismatch repair (dMMR) and efficacy outcomes of irinotecan-based first-line chemotherapy in patients with metastatic colorectal cancer (mCRC). Among 297 patients with sporadic mCRC receiving an irinotecan-containing regimen as first-line chemotherapy, 197 with available paraffin-embedded tissues were included in the current analysis. Tumors displaying loss of MMR protein (MLH1 or MSH2) and/or a microsatellite instability-high (MSI-H) genotype by PCR were classified as dMMR. Deficient mismatch repair was found in 23 evaluable tumors, among which eight displayed negativity for MLH1 expression, 11 for MSH2 expression, and four for both. The overall response rate was 47.2% (46.0% in proficient MMR (pMMR) and 56.5% in dMMR), with no significant difference between the two groups (P = 0.569). Median progression-free survival was 8.85 months in patients with dMMR tumors and 6.82 months in patients with pMMR tumors, but this difference did not reach statistical significance (P = 0.089). Median overall survival was not different between the two groups (P = 0.413). Efficacy outcomes of first-line irinotecan-based chemotherapy did not differ significantly between mCRC patients with pMMR and those with dMMR. Our data collectively indicate that MMR status is not effective as a single predictive marker for response to irinotecan-based chemotherapy in mCRC patients.     

Molecular patterns in deficient mismatch repair colorectal tumours: results from a French prospective multicentric biological and genetic study

Background:

To test the prognostic value of tumour protein and genetic markers in colorectal cancer (CRC) and examine whether deficient mismatch repair (dMMR) tumours had a distinct profile relative to proficient mismatch repair (pMMR) tumours.

Methods:

This prospective multicentric study involved 251 stage I–III CRC patients. Analysed biomarkers were EGFR (binding assay), VEGFA, thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) expressions, MMR status, mutations of KRAS (codons 12–13), BRAF (V600E), PIK3CA (exons 9 and 20), APC (exon 15) and P53 (exons 4–9), CpG island methylation phenotype status, ploidy, S-phase, LOH.

Results:

The only significant predictor of relapse-free survival (RFS) was tumour staging. Analyses restricted to stage III showed a trend towards a shorter RFS in KRAS-mutated (P=0.005), BRAF wt (P=0.009) and pMMR tumours (P=0.036). Deficient mismatch repair tumours significantly demonstrated higher TS (median 3.1 vs 1.4) and TP (median 5.8 vs 3.5) expression relative to pMMR (P<0.001) and show higher DPD expression (median 14.9 vs 7.9, P=0.027) and EGFR content (median 69 vs 38, P=0.037) relative to pMMR.

Conclusions:

Present data suggesting that both TS and DPD are overexpressed in dMMR tumours as compared with pMMR tumours provide a strong rationale that may explain the resistance of dMMR tumours to 5FU-based therapy.     

Serum HCG beta,CA 72-4 and CEA are independent prognostic factors in colorectal cancer

In colorectal cancer, stage is considered to be the strongest prognostic factor, but also serum tumour markers have been reported to be of prognostic value. The aim of our study was to investigate the prognostic value of serum carcinoembryonic antigen (CEA), CA 19-9, CA 242, CA 72-4 and free beta subunit of human chorionic gonadotropin (hCG beta) in colorectal cancer. Preoperative serum samples were obtained from 204 colorectal cancer patients, including 31 patients with Dukes' A, 70 with Dukes' B, 49 with Dukes' C and 54 with Dukes' D cancer. The serum levels of CEA, CA 19-9, CA 242 and CA 72-4 were measured with commercial kits with cut-off values of 5 microg/L for CEA, 37 kU/L for CA 19-9, 20 kU/L for CA 242 and 6 kU/L for CA 72-4. The serum hCG beta was quantitated by an immunofluorometric assay (IFMA) with 2 pmol/L as a cut-off value. Survival analyses were performed with Kaplan-Meier life tables, log-rank test and Cox proportional hazards model. The sensitivity was 44% for CEA, 26% for CA 19-9, 36% for CA 242, 27% for CA 72-4 and 16% for hCG beta. The overall 5-year survival was 55%, and in Dukes' A, B, C and D cancers the survival was 89%, 77%, 52% and 3%, respectively. Elevated serum values of all markers correlated with worse survival (p < 0.001). In Cox multivariate analysis, the strongest prognostic factor was Dukes' stage (p < 0.001), followed by tumour location (p = 0.002) and preoperative serum markers hCG beta (p = 0.002), CA 72-4 (p = 0.003) and CEA (p = 0.005). In conclusion, elevated CEA, CA 19-9, CA 242, CA 72-4 and hCG beta relate to poor outcome in colorectal cancer. In multivariate analysis, independent prognostic significance was observed with hCG beta, CA 72-4 and CEA.     

Prognostic significance of defective mismatch repair and BRAF V600E in patients with colon cancer

PURPOSE: Colon tumors with defective DNA mismatch repair (dMMR) have a well-characterized phenotype and accounts for approximately 15% to 20% of sporadic colon cancer as well as those colon cancer patients with Lynch syndrome. Although the presence of dMMR seems to be a favorable prognostic marker, data suggest that these patients do not respond as well to adjuvant chemotherapy. EXPERIMENTAL DESIGN: In this study, we examined the prognostic significance of tumor MMR deficiency and the presence of a specific mutation in BRAF (V600E) in a group of patients (n = 533) who participated in a randomized prospective clinical trial through the North Central Cancer Treatment Group. RESULTS: Tumors with dMMR were found to be associated with higher tumor grade (P = 0.001), proximal location (P < 0.0001), and improved overall and disease-free survival (P = 0.05 and 0.04, respectively). Among all cases examined, evaluation of the BRAF V600E mutation status revealed no statistically significant differences in either disease-free or overall survival. Patients were then grouped into four categories for further analysis: dMMR/BRAF(-), dMMR/BRAF(+), pMMR/BRAF(-), and pMMR/BRAF(+). The dMMR/BRAF(-) group had a significantly improved overall survival (5-year overall survival of 100% versus 73%, P = 0.002) compared with all others. The remaining three groups had very similar survival outcomes. An additional cohort of tumors previously classified as having dMMR were also tested for the BRAF V600E alteration. Results remained significant (P = 0.006) when the two groups were combined for analysis. CONCLUSIONS: Overall, these data suggest that the underlying molecular etiology of those tumors having dMMR may influence the disease outcome in these patients.     

胃癌患者CEA与Ki-67的表达及意义

目的研究胃癌患者血清CEA水平及肿瘤组织中Ki-67的表达情况及与生物学行为和预后的关系。方法回顾性分析110例胃癌患者的血清CEA水平与肿瘤组织Ki-67表达情况,并分析两者与临床病理特征及预后的关系。结果血清CEA及胃癌组织Ki-67阳性率分别为37．27％、75．45％。血清CEA水平与胃癌浸润深度、淋巴结转移及TNM分期有关（P〈0．05）,浸润至肌层以上、淋巴结阳性、TNM分期越高其阳性率越高。而Ki-67表达只与胃癌浸润深度有关（P〈0．05）,随着浸润深度增加,Ki-67阳性率增高。两者在胃癌患者中的表达呈正相关（r=0．265,P〈0．05）。两者联合检测与胃癌浸润深度、淋巴结转移和TNM分期关系密切（P〈0．05）,随着浸润深度、淋巴结转移数、TNM分期的增加,两者双阳性率增高。CEA阳性组、Ki-67阳性组的复发风险明显较高（P〈0．05）。CEA及Ki-67双阳性组患者的复发风险明显高于非双阳性组（P〈0．05）。结论联合检测血清CEA及肿瘤组织Ki-67可作为临床评价胃癌患者预后的指标。