结直肠癌患者肿瘤组织中KRAS、NRAS和BRAF基因突变的分子病理检测分析

目的：探讨结直肠癌患者肿瘤组织中KRAS、NRAS和BRAF基因各亚型突变状况。方法：应用Taqman-ARMS方法检测101例结直肠癌患者石蜡组织中KRAS、NRAS、BRAF基因突变情况。结果：结直肠癌患者肿瘤组织中KRAS基因总突变率为42.57%,其中30例(29.70%)检测到外显子2第12密码子突变;其中13例(12.87%)检测到KRAS基因外显子2第13密码子突变,为G13D点突变,未检测到G13C点突变;NRAS基因总突变率为3.96%,其中外显子2第12密码子突变1例(0.99%),外显子2第13密码子突变1例(0.99%),外显子3第61密码子突变2例(1.98%);BRAF基因总突变率为3.96%。结论：结直肠癌患者组织中KRAS基因突变率较高,NRAS和BRAF基因突变率虽低但不容忽视。KRAS、NRAS和BRAF基因检测人群的筛选对结直肠癌患者治疗方案的选择意义重大,能够更有效的指导精准医学个体化治疗。     

结直肠癌患者BRAF,KRAS,NRAS和PIK3CA基因突变与其病理正的关系

目的:探讨265例结直肠癌患者BRAF,KRAS,NRAS和PIK3 CA基因突变及其病理特征关系.方法:选取2014年12月至2016年12月的265例结直肠癌患者肿瘤组织标本进行回顾性分析,采用PCR扩增-直接测序法检测BRAF基因(1 5外显子600密码子),KRAS基因(12,13,61密码子突变),NRAS(2号与3号外显子的12密码子、13密码子与61密码子常见的12个突变位点)及PIK3 CA(第9,20外显子)基因的突变状态,分析其与结直肠癌临床病理特征的关系.结果:265例患者中存在BRAF基因突变率为6.8％(18/265),KRAS基因突变率为32.1％(85/265),NRAS基因突变率为5.7％(15/265),PIK3 CA基因突变率为11.3％(30/265).NRAS基因和KRAS基因突变与年龄有关(P＜0.05),与性别、原发部位、组织学类型、分化程度、TNM分期、区域淋巴结转移、远处转移、术后复发转移均无关(P＞0.05);BRAF,PIK3 CA基因在原发部位为右半结肠患者中的突变率明显升高(P＜0.05),但与年龄、性别、组织学类型、分化程度、TNM分期、区域淋巴结转移、远处转移、术后复发转移均无关(P＞0.05).结论:NRAS,PIK3 CA基因在中国结直肠癌患者中的突变率较低.KRAS,NRAS基因突变与年龄相关,BRAF,PIK3 CA基因与肿瘤原发部位相关,联合检测这些基因的突变情况可以判断疾病的发生发展.     

252例结直肠癌组织中KRAS、NRAS、BRAF、PIK3CA的基因突变分析

目的分析结直肠癌(colorectal cancer,CRC)组织中KRAS、NRAS、BRAF和PIK3CA基因的常见突变类型及其与临床病理指标的关系。方法对252例CRC石蜡包埋组织进行DNA提取,采用Sanger测序法对KRAS、NRAS、BRAF和PIK3CA基因进行检测,分析各个基因的突变率与临床病理特征的关系,并统计各个基因的突变类型。结果 252例CRC中,KRAS、BRAF、NRAS和PIK3CA突变发生率在性别、年龄、肿瘤部位、病理分期和有无淋巴结转移上差异均无统计学意义(P0.05);检测阳性突变共140例(55.5%),其中KRAS 113例(44.8%),NRAS 1例(0.4%),BRAF 19例(7.5%),PIK3CA 28例(11.1%),包括PIK3CA与KRAS、NRAS、BRAF基因发生双突变21例(8.3%);KRAS的主要突变类型包括G12A、G12C、G12D、G12R、G12S、G12V、G13D、T20M、A59T、Q61H、Q61L、Q61P;NRAS仅有1例突变为G12D;BRAF的主要突变类型为V600E、D594G、K601E;PIK3CA的主要突变类型包括E542K、E545K、Q546K、Q546P、Q546R、M1043I、H1047R。PIK3CA与KRAS、NRAS、BRAF之间会发生交叉突变,但KRAS、NRAS、BRAF三者之间基本不存在交叉突变。结论 CRC中KRAS阳性突变率居高,PIK3CA次之,BRAF、NRAS突变率最低,且PIK3CA常与KRAS、NRAS、BRAF发生交叉突变。对CRC患者行KRAS、NRAS、BRAF、PIK3CA等多基因检测,可正确指导并选择抗EGFR单抗药,从而实现真正意义上的个体化靶向治疗。     

结直肠癌前病变与结直肠腺癌免疫表型及基因突变分析

目的 分析结直肠癌前病变与结直肠腺癌免疫表型及基因突变特征,比较两种结直肠癌前病变癌变机制的差异.方法 收集2006年1月至2012年6月间诊断的53例结直肠锯齿状病变,包括30例增生性息肉、20例广基锯齿状腺瘤(SSA)及3例混合性息肉;同时选取45例传统腺瘤、50例结直肠腺癌.采用免疫组织化学EnVision法检测30例增生性息肉、20例SSA、3例混合性息肉以及45例传统腺瘤DNA错配修复(MMR)蛋白MLH1、MSH2、MSH6及甲基转移酶MGMT蛋白的表达情况;采用Sanger直接测序法检测10例SSA、10例传统腺瘤、l例混合性息肉及50例结直肠腺癌中KRAS、BRAF及PIK3CA基因的突变情况.结果 (1)MLH1蛋白在增生性息肉中仅3例阴性(10％),在SSA、传统腺瘤中均呈阳性.MSH2、MSH6及MGMT蛋白在增生性息肉及SSA中的阴性率明显高于传统腺瘤,差异均具有统计学意义(P＜O.01).(2)结直肠SSA和传统腺瘤中KRAS基因突变比例为5/10,5/10;1例混合性息肉存在KRAS基因突变.(3)结直肠腺癌中,KRAS、BRAF及PIK3CA基因突变率分别为48％ (24/50)、6％ (3/50)及4％(2/50).结论 结直肠锯齿状病变与传统腺瘤在免疫表型及基因突变等方面存在着一定的差异,MMR与MGMT在“锯齿状肿瘤”癌变通路中起着重要的作用.KRAS基因突变是结直肠腺癌癌变过程中发生较早的重要遗传学改变.     

中国结直肠癌、肺癌和胃癌患者KRAS基因突变情况分析

目的探讨中国结直肠癌、肺癌和胃癌中KRAS基因的突变特征及其与临床病理特征的关系,并比较基因突变在三种癌症间的异同。方法采用直接测序法检测860例结直肠癌、101例肺癌和96例胃癌组织中KRAS基因第2号外显子的突变。结果 KRAS基因突变率在肺癌、胃癌、结直肠癌中的差异均有显著性(5.9%vs 4.2%vs 35.1%,P0.05)。三种肿瘤中,KRAS基因突变均以第12密码子为主。KRAS突变与患者年龄、性别无明显相关性。肺腺癌患者KRAS基因突变高于非腺癌包括鳞癌等(10.2%vs 0,P0.05)。肠腺癌和黏液腺癌中KRAS基因突变率显著高于其它类型结直肠癌(35.7%vs 37.6%vs 8%,P0.05)。结论结直肠癌患者的KRAS基因突变率显著高于肺癌和胃癌。因此,KRAS基因突变检测可能对结直肠癌患者的个体化靶向治疗具有更为重要的指导意义。     

2771例肺肿瘤临床病理特征分析

目的：根据WHO(2015版)肺肿瘤组织学分类标准,探讨军事医学科学院附属医院肺肿瘤的病理类型及分布特点。方法：收集2010年11月1日至2015年3月31日病理诊断2771例肺肿瘤,复习其临床资料、HE切片及免疫组织化学切片。按WHO(2015版)分类标准进行病理诊断及分类。结果：2771例肺肿瘤中多数为男性1671例(60.30%),少数为女性1100例(39.70%);左肺1286例(46.41%)、右肺1456例(52.54%)、双肺29例(1.05%);年龄16~91岁。腺癌1622例(58.53%)、鳞癌424例(15.30%)、腺鳞癌32例(1.15%)、神经内分泌肿瘤465例(16.78%)、大细胞癌19例(0.69%)、梭形细胞癌1例(0.04%)、巨细胞癌1例(0.04%)、癌肉瘤17例(0.61%)、淋巴上皮样癌1例(0.04%)、唾液腺型肿瘤4例(0.14%)、腺瘤11例(0.40%)、间叶性肿瘤55例(1.98%)、淋巴瘤7例(0.25%)、异位起源性肿瘤13例(0.47%)、转移性肿瘤99例(3.57%)。非小细胞肺癌-非特指型,倾向于腺癌小活检中TTF-1抗体阳性率为92.60%(1263/1364)、NapsinA抗体阳性率为97.07%(1324/1364);非小细胞肺癌-非特指型,倾向于鳞癌小活检中CK5/6阳性率为96.99%(290/299)、P40阳性率为98.51%(66/67)、P63阳性率为93.72%(343/366)。非小细胞肺癌分子亚型首次活检中EGFR基因突变率34.77%(378/1087),KRAS基因突变率2.92%(24/823),BRAF基因突变率0.87%(5/572),ALK融合基因阳性率11.99%(41/342),ALK-D5F3抗体阳性率22.23%(66/296),ROS1融合基因阳性率2.56%(7/273),c-Met基因扩增率4.40%(12/273),c-Met基因突变率6.67%(1/15),Her-2基因突变率0.73%(2/273),PIK3CA基因突变率13.33%(2/15),PTEN基因突变率6.67%(1/15),RET融合基因阳性率0(0/15)和NTRK1融合基因阳性率0(0/15)。二次活检率EGFR基因4.76%(18/378),ALK融合基因2.44%(1/41)。结论：肺肿瘤在男性患者中高发,病变部位最常见于右肺,腺癌已经成为最常见的病理类型。首次活检中非小细胞肺癌驱动基因中EGFR基因、ALK融合基因存在较高的突变率,其他基因突变率虽低但不容忽视。二次活检率较低,需引起重视。     

RAS突变和微卫星不稳定与Ⅲ期结直肠癌患者临床病理特征及预后的相关性分析

目的:检测Ⅲ期结直肠癌患者中RAS和BRAF基因突变以及微卫星不稳定(microsatellite instability,MSI)状态,并分析其临床病理关系及预后。方法:收集2010~2015年广东省人民医院共281例经病理学证实的Ⅲ期结直肠癌组织标本,采用PCR-Sanger测序法和免疫组织化学法对石蜡切片进行分析,检测RAS/BRAF基因突变和MSI状态,并探讨其与结直肠癌临床病理特征和预后的关系。结果:281例患者中,RAS/BRAF突变率为48.4%(136/281),其中KRAS突变率最高(116/281,41.3%)。RAS/BRAF基因突变与癌胚抗原水平密切相关(P0.05)。免疫组织化学法检测到高度MSI(MSI-H)患者18例(6.4%),MSI-H状态在淋巴结转移N2b期患者中更为常见(P0.05)。BRAF基因在MSI-H肿瘤中的突变率较高(P0.01)。RAS/BRAF野生型或者MSI-H患者的总生存期和无进展生存期均明显高于突变型或低度MSI/微卫星稳定患者。结论:RAS/BRAF突变和MSI检测有助于结直肠癌生物学行为分析和患者预后判断。     

非小细胞肺癌中九基因联合检测突变分析

目的通过ARMS-PCR法联合检测非小细胞肺癌(non-small cell lung cancers, NSCLC)中9个驱动基因(ALK、ROS1、RET、EGFR、KRAS、HER-2、PIK3CA、NRAS和BRAF)的突变情况,分析其突变状态及临床意义。方法采用ARMS-PCR技术检测2018年2月～2019年2月陆军军医大学第一附属医院病理科存档的522例NSCLC肿瘤组织中的9个驱动基因的突变情况。结果 522例NSCLC中ALK、ROS1和RET的融合突变率分别为5.17%、1.34%、1.34%,EGFR、KRAS、HER-2、PIK3CA、NRAS和BRAF的突变率分别为47.32%、7.28%、1.72%、1.72%、0.95%和0.57%。女性患者中EGFR突变和ALK融合突变率明显高于男性患者(P0.001),而KRAS突变率低于男性患者(P0.001)。EFGR和KRAS突变在肺腺癌中显著高于肺鳞癌(P0.001)。无吸烟史患者中EGFR突变和ALK融合发生率均高于吸烟患者(P0.001),KRAS突变在吸烟患者的发生率显著高于无吸烟史患者。利用ARMS法联合检测9个基因在单点检测EGFR基础上增加了10.15%的患者可使用靶向药物(P0.01)。结论在9个驱动基因突变中,EGFR突变、ALK融合、KRAS突变与患者性别、吸烟以及组织学类型密切相关,其它较为罕见驱动基因突变并未发现与组织学类型、患者性别及吸烟与否相关。九基因联合检测可作为NSCLC更简便适用的药物靶向检测方法。     

结直肠癌原发灶与肝转移灶中KRAS、PIK3CA基因突变的一致性分析

目的探讨结直肠癌原发灶及相应肝转移灶中KRAS、PIK3CA基因突变及临床意义。方法采用实时荧光定量PCR法检测58例结直肠癌原发灶癌组织及相应肝转移灶组织中KRAS、PIK3CA基因突变情况。结果结直肠癌原发灶与肝转移灶中KRAS基因的突变率分别为31.03%(18/58)、25.86%(15/58),最常见的突变位点为G12D;PIK3CA基因的突变率分别为8.62%(5/58)、10.34%(6/58),最常见的突变位点为E545K。有1例同时发生KRAS(G12D)、PIK3CA(E545K)基因突变。结直肠癌原发灶与肝转移灶中KRAS、PIK3CA基因突变的一致性较好。单因素分析显示:KRAS突变与结直肠癌原发灶肿瘤部位、转移灶多少、大体类型相关(P0.05),PIK3CA突变与同时性/异时性肝转移、转移灶多少相关(P0.05)。多因素Cox回归模型显示:同时性/异时性肝转移、KRAS突变状态是影响结直肠癌预后的危险因素。结直肠癌同时性肝转移比异时性肝转移患者的总生存期延长,KRAS野生型比突变型患者总生存期延长(P0.05)。结论结直肠癌中KRAS基因G12D位点突变率最高,原发灶与肝转移灶中KRAS、PIK3CA基因突变一致性较好。原发灶可以作为分子检测的标本来源,基于精准医疗对于靶向治疗的选择,则需再次评估肝转移灶中的基因状态,以达到个体化治疗。     

结直肠癌中的BRAF基因突变

约15%结直肠癌患者有BRAF基因突变。BRAF通过激活MAPK通路和抑制促凋亡因子BIM,导致细胞异常增殖和分化。结直肠癌的"锯齿状"成瘤途径,即"畸形隐窝灶-增生性息肉-锯齿状腺瘤-癌"途径。BRAF基因突变参与这条途径并与CpG岛甲基化和微卫星不稳定性均有密切关系。KRAS基因状态为预测抑制表皮生长因子受体的单克隆抗体临床疗效的分子标记物,有研究发现一部分KRAS未发现突变而存在BRAFV600E基因突变的患者对爱必妥等药物也无效,故野生型BRAF基因对爱必妥等药物的有效性也是必需的。近年来也出现针对突变型KRAS和BRAF的分子靶向抑制剂,除了表皮生长因子受体抑制剂,分子靶向药物使有BRAF/KRAS突变的患者有了更多的选择。     

Frequent activating GNAS mutations in villous adenoma of the colorectum

To elucidate the role of GNAS mutations in colorectal tumourigenesis, we performed a mutation analysis in a total of 234 colorectal tumours, including adenomas, serrated lesions and adenocarcinomas. Activating GNAS mutations were found in 20 of the 24 villous adenomas (83%) but were absent in all the other tumours, except for one tubulovillous adenoma (3%) and two adenocarcinomas (3%). KRAS and BRAF mutations were always mutually exclusive. KRAS mutations were frequent in villous (67%) and tubulovillous (60%) adenomas but were rare or absent in tubular adenomas (6%) and serrated lesions, including hyperplastic polyps, sessile serrated polyps/sessile serrated lesions and traditional serrated adenomas (0-9%). BRAF mutations were found in four villous adenomas (17%) and in the large majority of serrated lesions (81-92%), but were absent in tubular and tubulovillous adenomas. Seventeen villous adenomas (71%) harboured GNAS mutations concomitantly with KRAS or BRAF mutations. Immunohistochemically, all the villous adenomas retained mismatch repair protein expression, suggesting that they are microsatellite-stable. The current study showed that the presence of activating GNAS mutations, in association with KRAS or BRAF mutations, is a characteristic genetic feature of colorectal villous adenoma.     

Colorectal polyps in autopsy material. Part I. Adenomatous polyps.

In prospective studies specimens of the large bowel were obtained from 733 autopsy cases. After fixing they were examined under illuminated magnifying lens and all polypous lesions were excised for histological analysis and classified according to Correa's criteria (8). Adenomatous polyps were found in 280 cases (38.2%) and their prevalence increased with age in both sexes. Adenomatous polyps, also multiple were found most frequently in the transverse colon, and then ascending colon, sigmoid, descending colon and rectum. The mean number of adenomatous polyps per positive specimen was 2.33 for men and 2.60 for women. In 6.8% their diameter was > or = 10 mm. The prevalence of polyps with severe degree of dysplasia (III degree) increased from proximal to distal segments of the colon in both sexes and their prevalence is significantly higher in the ascending colon in women. In the whole series there were 6 adenocarcinomas of 5-18 mm in size, all in women over 80 years of age. The results of the present study were compared with the data concerning other populations of the world. In the light of a repeatedly confirmed a generally accepted relationship between adenoma and adenocarcinoma of the large intestine the results of our study seem to underestimate the prevalence of colon adenocarcinoma in the population of Cracow and Cracow district.     

甲状腺乳头状癌中TROP-2表达的临床意义及其诊断价值

目的观察人类滋养层细胞表面抗原2(TROP-2)在甲状腺乳头状癌(papillary thyroid carcinoma,PTC)中的表达,探讨TROP-2在PTC中表达的临床意义及其诊断价值。方法采用免疫组化EnVision法检测100例甲状腺恶性病变(PTC 75例、滤泡性癌10例、髓样癌10例、差分化癌5例)、45例良性病变(正常甲状腺10例、结节性甲状腺肿10例、桥本甲状腺炎15例、滤泡性腺瘤10例),5例具有乳头样核特征的非浸润性甲状腺滤泡性肿瘤(non-invasive folliculaRthyroid neoplasms with papillary-like nucleaRfeatures,NIFTP)中TROP-2的表达;ARMS法检测PTC中BRAF V600E基因突变。分析TROP-2对PTC诊断的敏感性和特异性,及其与PTC临床病理特征以及BRAF V600E基因突变的关系。结果TROP-2在PTC中的阳性率为81.3%(61/75),在其他甲状腺恶性肿瘤和良性病变中均阴性,TROP-2对PTC诊断的敏感性为81.3%,特异性为100%。TROP-2表达与PTC淋巴结转移有关(P<0.05),与患者年龄、性别、肿瘤部位及临床分期无关(P>0.05),经典型PTC中TROP-2表达高于滤泡亚型PTC(P<0.05)。PTC中TROP-2表达与BRAF V600E基因突变呈正相关(P<0.05)。结论TROP-2是一种具有高度特异性和敏感性的诊断PTC的标志物,TROP-2检测可预测PTC的临床生物学行为和BRAF V600E基因突变状态,并对于形态学变形的PTC、微小型PTC和PTC的甲状腺内扩散的诊断和识别具有重要价值。     

Serrated polyps of the large intestine: a molecular study comparing sessile serrated adenomas and hyperplastic polyps

Aims:  To compare the molecular profile of a series of sessile serrated adenomas (SSAs) and hyperplastic polyps (HPs), in order to distinguish these lesions, SSAs having a potential role in the genesis of serrated adenocarcinomas through a serrated pathway in which methylation plays a key role.
Methods and results:  Twelve HPs and sixteen SSAs of the right and left colon were investigated for microsatellite instability, DNA mismatch repair genes, p53, p16, and β-catenin expression, MLH1 and p16 ( CDKN2A ) gene methylation, and KRAS and BRAF mutations. Both SSAs and HPs were microsatellite stable. MLH1 and MSH2 protein silencing , aberrant cytoplasmic expression and methylation of p16 were found to be exclusive to right-sided SSAs. The MLH1 promoter gene was frequently methylated in right-sided SSAs in contrast with HPs. Abnormal p53 and β-catenin expression was present in both SSAs and HPs. BRAF and KRAS mutation were mutually exclusive, but KRAS mutation was present only in left-sided SSAs and HPs.
Conclusions:  HPs and SSAs may be related lesions. However, at least right-sided SSAs differ from left-sided SSAs and HPs in the occurrence of MLH1 and p16 methylation, supporting the hypothesis that SSAs could be precursors of serrated adenocarcinomas.     

Deletion mutation of BRAF in a serrated adenoma from a patient with familial adenomatous polyposis

BRAF gene mutations in the colorectum have been associated with serrated adenomas and less frequently with hyperplastic polyps, villous adenomas, tubular adenomas, and carcinomas. Most BRAF mutations in the colon have been reported as a V600E substitution. We report a case with a very rare deletion mutation of BRAF (c.1799-1801delTGA, p.Val600_Lys601delinsGlu) in a serrated adenoma; the patient has familial adenomatous polyposis with a germline mutation of the APC gene (c.3578delA, p.Gln1193ArgfsX1264). Genetic studies on fundic gland polyps and tubular adenomas from the same patient failed to demonstrate BRAF mutation. This case is the first reported with a deletion mutation of BRAF found in the colon.     

Monoclonal antibody to a human pancreatic carcinoma cell line recognizes gastrointestinal neoplasms.

A monoclonal antibody designated RWP1.1 was produced against a human pancreatic carcinoma cell line RWP1. This antibody was shown to recognize an epitope of carcinoembryonic antigen. The reactivity of the antibody was evaluated on formalin-fixed normal tissues, 86 malignant neoplasms, 10 colonic polyps, and 6 cases of chronic pancreatitis using the peroxidase anti-peroxidase technique. RWP1.1 did not react with normal tissues apart from weak staining of fetal pancreatic ducts. This antibody preferentially reacted with primary and metastatic adenocarcinomas of the colon, stomach, pancreas, and colonic polyps but not with most adenocarcinomas from other sites nor with other types of tumors or cases of chronic pancreatitis. It also reacted with colon adenocarcinomas on frozen sections. The restricted specificity of this antibody could be used in differentiating gastrointestinal adenocarcinomas from other types of tumors including adenocarcinomas from other sites and most pancreatic adenocarcinomas from chronic pancreatitis.     

Morphological characteristics of stromal gastrointestinal tumors

Stromal tumors are singled out from smooth muscle and neurogenic neoplasms into a special group due to differences in CD117 expression caused by mutation of c-kit gene. Out of 57 stromal tumors, 37 (64,9%) located in the stomach, 17 (29,8%) in the small intestine and 3 (5,3%) in the colon. Immunohistochemically, all the tumors expressed CD117 and vimentine. Smooth muscle actin was found in 82% tumors, S-100 protein in 75%, neuron-specific enolase in 66% cases. Malignant tumors were in 93% cases, and in 7% benign. Metastases were observed in 47.7% cases, recurrences in 14%. The liver was most frequent site of metastases (88.9%), peritoneum (51.9%). 21% patients died of progression of the underlying disease during the follow-up of 6-60 months.     

p110δ突变失活的ApcMin/+结直肠癌癌前病变小鼠模型的建立

 目的：建立p110δ突变失活的ApcMin/+结直肠癌癌前病变小鼠模型,为研究p110δ在小鼠结直肠癌癌前病变中的作用提供实验模型。方法：将C57BL/6J背景的ApcMin/+结直肠癌癌前病变小鼠与p110δ突变失活小鼠（p110δD910A/D910A）进行杂交建系,通过PCR技术鉴定子代小鼠基因型,获得p110δ突变失活的ApcMin/+小鼠。对适龄小鼠进行肠道取材,亚甲蓝染色后,观察肠道结构,对腺瘤和微腺瘤进行统计。肠道组织进行石蜡包埋、切片,做HE染色进行进一步观察。结果：获得p110δ突变失活的ApcMin/+杂交鼠（ApcMin/+;p110δD910A/D910A）并得以稳定传代。ApcMin/+;p110δD910A/D910A杂交小鼠的肠道组织中,腺瘤数目和体积比ApcMin/+结直肠癌癌前病变小鼠均有减少。结论：成功建立p110δ突变失活的ApcMin/+结直肠癌癌前病变小鼠模型,并得到小鼠肠道肿瘤的初步表型,为进一步研究p110δ在肠道肿瘤发生发展中的作用提供重要的工具动物。     

Expression of survivin in normal, hyperplastic, and neoplastic colonic mucosa

The regulation of apoptotic cell death may have a profound effect on the pathogenesis and progression of colon cancer. Survivin, a member of the inhibitor of apoptosis gene family, has been detected in fetal tissue and in a variety of human malignancies. In the current study, we investigated survivin expression by an immunohistochemical approach in benign, hyperplastic, premalignant, and malignant lesions of the colon. Survivin was detected in all cases of normal colonic mucosa (20/20), hyperplastic polyps (20/20), adenomatous polyps (20/20), and in both well differentiated and moderately differentiated colonic adenocarcinomas (20/20). In the normal colonic mucosa, survivin expression was mostly restricted to the base of the colonic crypts. All epithelial cells showed uniformly intense staining for survivin in hyperplastic polyps. By contrast, adenomas and adenocarcinomas showed a heterogeneous staining pattern with cell-to-cell, gland-to-gland, and regional variability in the intensity of survivin staining. In contrast to the basal preponderance of staining in normal colonic mucosa, numerous survivin positive cells were present at the luminal surface of hyperplastic polyps, adenomatous polyps, and adenocarcinomas. In conclusion, the expression of survivin is not a specific marker of adenocarcinoma of the colon but does show characteristic and reproducible patterns of expression in non-neoplastic proliferative lesions and in normal colonic mucosa.     

Hyperplastic polyps of the colon and rectum – reclassification,BRAF and KRAS status in index polyps and subsequent colorectal carcinoma

Hyperplastic polyps (HP) of the colon and rectum were previously considered benign. Newer studies have suggested that colorectal HP are different entities. The aim of this study was to reclassify lesions from a 5‐year period previously classified as colorectal HP into traditional hyperplastic polyp (THP), sessile serrated lesions (SSL), and other lesions. All patients were confirmed in the Danish National Pathology Database for the occurrence of metachronous polyps/adenomas, colorectal cancer (CRC), and other gastrointestinal malignancies. Molecular pathology of the CRC were characterized and correlated with the index lesion. In total, 591 HP biopsy specimens were obtained from 480 patients. The lesions were reclassified as: 358 THP, 109 SSL, 35 TA, 81 unspecified non‐neoplastic lesions, four traditional serrated adenoma, and 4 SSL with cytological dysplasia. Seven patients developed CRC in the follow‐up period (1 patient had SSL, 4 had THP, and 2 had unspecified non‐neoplastic lesions). Ten patients developed other gastrointestinal malignancies. The patient with SSL as index lesions who developed CRC harbored V600E BRAF mutation in both index lesion and the carcinoma. Sixteen percent of patients with SSL subsequently developed a neoplastic lesion. Further studies are needed to clarify the cancer risk of SSL.