宫颈液基细胞学与DNA倍体分析诊断宫颈鳞状上皮内病变的准确性

目的 探讨用DNA倍体分析(DNA-ICM)和宫颈液基细胞学(LBC)诊断宫颈鳞状上皮内病变的准确性.方法 选取组织学诊断的鳞状上皮内病变或宫颈癌病例中LBC和/或DNA-ICM结果异常的病例,进行组织学与LBC和/或DNA-ICM结果对比.LBC诊断以非典型鳞状细胞-意义不明确(ASC-US)/非典型腺细胞(AGC)为切入点;DNA-ICM以≥3个细胞、DNA指数≥2.5为切入点;以组织学诊断结果为金标准,应用SAS V8数据分析.结果 DNA-ICM与LBC对宫颈上皮内瘤变(CIN)筛查的敏感性,分别为84.9％和79.5％(P＞0.05);两种方法结合筛查敏感性可达97.5％,高于独立应用一种方法的敏感性.188例同时进行了LBC和DNA-ICM检测的病例中,DNA-ICM阳性176例,其中组织学诊断炎性病变52例,CIN、阴道上皮内瘤变(VIN)和宫颈癌121例,其他类型病变3例;在组织学诊断为炎性病变的病例中LBC阳性率为46.2％,在CIN、VIN和宫颈癌的病例中阳性率为72.7％ (P＜0.01).LBC诊断ASC-US的52例中,组织学最终诊断炎性病变20例,CIN 32例;DNA-ICM在炎性病变和CIN病例的阳性率分别为75％ (15/20)和96.9％ (31/32)(P＜0.05).结论 DNA-ICM具有和LBC相似的筛查敏感性,两种方法相结合敏感性可显著提高;LBC可协助分流DNA-ICM的假阳性病例,提高DNA-ICM的特异性;DNA-ICM有利于鉴别LBC的不确定诊断.     

食管鳞癌中有活性的激酶C受体表达与临床病理参数的关系

目的 研究有活性的激酶C受体(RACK1)在食管鳞癌组织中的表达水平及其临床意义.方法 Western印迹检测食管鳞癌细胞中RACKI的表达.免疫组织化学方法检测组织芯片中113例食管鳞癌组织及其配对的癌旁正常食管黏膜中RACKl和Ki67蛋白的表达水平.将病例按年龄、性别、肿瘤部位、吸烟与否、分化程度和TNM分期进行分组,比较不同组别中RACKl表达水平的差异.结果 RACKl在食管鳞癌组织中的表达低于癌旁正常食管黏膜,差异具有统计学意义(x2=63.363,P<0.01).不吸烟组的肿瘤组织中RACKl高表达率为72.5%(29/40),高于吸烟组的46.6%(34/73)(X2=7.040,P=0.008).TNM l期和Ⅱ期患者的肿瘤组织中RACKl高表达率为63.8%(44/69),高于TNMⅢ期的43.2%(19/44)(0=4.616,P=0.032).Ki67评分越高的肿瘤组织中RACKl的表达越低(x2=8.261,P=0.016).结论 RACKl在食管鳞癌中表达发生下调.食管鳞癌中RACKI的表达与吸烟、TNM分期及Ki67评分具有相关性.

Abstract：

Objective To explore the expression level and clinical significance of receptor for activated C kinase 1(RACKl)in esophageal squamous cell carcinoma(ESCC).Methods Western Blotting was performed to detect the RACKl expression in ESCC cell lines.Immunohistochemistry was conducted to assay the expression of RACKl and Ki67 in tumor tissues and adjacent normal epithelium from 113 ESCC patients in tissue microarray.The relationship between the RACKI level and such clinieopathologic profiles as age,gender,location,smoking,differentiation degree and TNM(tumor,node,metastasis)stage were analyzed.Results The expression of RACKl protein was significantly downregulated in ESCC tissues as compared with the normal adjacent epithelium(X2=63.363,P<0.01).An upregulated expression of RACKl was observed in 72.5%(29/40)ESCC tissues of patients without a smoking history.And it was significantly higher than that in 46.6%(34/73)of patients with a smoking history(x2=7.040,P=0.008).In addition,the rate of up-regulated of RACKl was significantly higher in stage I andⅡgroup(63.8%,44/69)than that in stage Ⅲ group(43.2%,19/44)(x2=4.616,P=0.032).Moreover.the ESCC tissues with a higher Ki67 score showed a lower level of RACKl than that with a lower Ki67 score(x2=8.261,P=0.016).Conclusions The expression of RACKl is down-regulated in ESCC tissues and it is associated with smoking,The expression of RACKl was associated with smoking,TNM staging and Ki67 score of ESCC.     

膀胱癌组织中染色体3q26.1小片段高频率缺失及其意义

目的 探讨人膀胱尿路上皮癌组织中染色体3q26.1小片段拷贝数改变及其临床意义.方法 采用微阵列比较基因组杂交(array comparative genomic hybridization,Array-CGH)技术分析35例膀胱癌组织(Ta～T118例,T2～T417例)基因组DNA(区段/基因)拷贝数改变.采用实时荧光定量PCR验证57例冻存膀胱癌组织(Ta～T125例,T2～T4 32例),34例甲醛固定石蜡包埋膀胱癌组织(Ta～T115例,T2～T419例),以及29例膀胱癌患者术前尿脱落细胞和15例健康志愿者尿脱落细胞中3q26.1小片段拷贝数的改变情况.结果 Array-CGH分析显示,膀胱癌组织中存在染色体3q26.1中一个小片段的高频率缺失,缺失率为77.1%(27/35).实时荧光定量PCR验证发现,57例膀胱癌冻存组织和34例膀胱癌固定包埋组织中该3q26.1小片段高频率缺失率分别为78.9%(45/57)和100.0%(34/34);膀胱癌患者术前尿脱落细胞中3q26.1小片段的相对拷贝数(中位数为0.0020)与正常对照组(中位数为0.0030)相比差异有统计学意义(P＜0.01).结论 染色体3q26.1小片段缺失是膀胱尿路上皮癌特征性的DNA分子水平异常改变.尿脱落细胞的3q26.1小片段缺失有可能成为膀胱癌的分子标志物.

Abstract：

Objective To investigate the copy number changes on chromosome 3q26. 1 in urothelial carcinoma of the bladder, and to explore its potential clinical significance. Methods The microarray-based comparative genomic hybridization (Array-CGH) approach was used to analyze the genome-wide copy number changes of 35 tumor tissue samples of bladder cancer. To confirm the loss of a small fragment in 3q26. 1 detected by Array-CGH, real-time fluorescent quantitative polymerase chain reaction (real-time PCR) was performed with 57 frozen tumor tissue samples and 34 formalinfixed paraffin-embedded (FFPE) tumor tissue samples. The urine sediment cells collected from 15 healthy volunteers and 29 bladder cancer patients were checked as above. Results The Array-CGH data showed that the copy number loss of a small fragment in 3q26. 1 was detected in 77.1% (27/35)of the tumor tissue samples investigated. Real-time PCR analysis validated this loss of a small fragment of 3q26.1 with high frequencies in both 57 frozen tumor samples and 34 FFPE tumor samples.The percentage of samples exhibiting loss was 78.9% (45/57) and 100. 0% (34/34) respectively.Furthermore, the relative copy number of the 3q26.1 small fragment was significantly lower in the urinary sediment cells of the patients (median=0. 0020), comparing with that of healthy controls (median=0. 0030) (P＜0.01). Conclusions Loss of the small fragment in 3q26.1 could be a characteristic genetic change of urothelial carcinoma of the bladder. It may serve as a potential molecular marker for bladder cancer.     

乳腺癌新辅助化疗前后组织病理学与分子标志物表达意义的探讨及对比分析

目的 探讨乳腺癌新辅助化疗前核芯针穿刺活检(CNB)标本和化疗后手术切除标本的病理类型、病理分级、分子标志物表达及其改变与治疗反应病理评价的关系.方法 收集209例接受新辅助化疗的乳腺癌患者CNB和手术切除标本,评价其病理类型、病理分级、治疗反应病理评价信息(MP分级系统);应用免疫组织化学方法 (MaxVision二步法)检测上述标本分子标志物雌激素受体(ER)、孕激素受体(PR)和HER2的表达信息,应用SPSS 15.0软件进行相关统计学分析.结果 (1)新辅助化疗后治疗反应病理评价分别为MP1级14例,MP2级35例,MP3级106例,MP4级36例,MP5级18例.(2)CNB标本的ER表达与治疗反应病理评价呈负相关(χ2=33.083,P=0.001);手术切除标本各类信息与治疗反应病理评价未见统计学相关性(P>0.05);(3)化疗后手术切除标本信息均可发生改变,病理类型、病理分级发生变化病例所占比例分别为6.8%(9/132)和34.9%(30/86);ER、PR、HER2表达发生改变的比例分别为42.4%(75/177)、55.4%(98/177)和26.6%(46/173),仅HER2表达改变的差异有统计学意义(P=0.049).上述信息改变与治疗反应病理评价无关(P>0.05).结论 CNB标本对预测肿瘤治疗反应的病理评价具有重要价值.化疗后肿瘤的信息均可发生改变,因此有必要在新辅助化疗后重复确认肿瘤组织的病理类型及病理分级,并应用免疫组织化学方法 重复检测化疗后手术切除标本的分子标志物表达.

Abstract：

Objective To investigate the relationship between the pathologic responses and histologic type, grade, the expression of ER, PR and HER2 and their changes in breast carcinoma before and after neoadjuvant chemotherapy (NAC). Methods Two-hundred and nine cases of breast cancer with NAC were analyzed and clinical, pathologic data were evaluated based on the Miller and Payne (MP) grading system. The expression of ER, PR and HER2 in the cancers before and after NAC were detected by immunohistochemistry (MaxVision method). SPSS 15.0 software was used to conduct statistical analysis. Results (1) Pathologic responses to the NAC were graded as MP1 (14 cases), MP2 (35 cases), MP3 (106 cases), MP4 (36 cases) and MP5 (18 cases); (2) The expression of ER in core needle biopsy had related negatively to the pathologic response (χ2=33.083, P=0.001). However, the histologic type, grade, ER and PR status, and HER2 expression in surgically-removed specimens had not related to the pathologic response (P>0.05); (3) After NAC, the pathologic type and grade changed in 6.8% (9/132) and 34.9% (30/86) of the cases, and the rates of changes in the expression of ER, PR and HER2 were 42.4% (75/177), 55.4% (98/177) and 26.6% (46/173), respectively. Only the expression of HER2 had significant difference between before and after neoadjuvant chemotherapy (P=0.049). The changes in other data had no relationship with the pathologic response (P>0.05). Conclusions Analysis of core needle biopsy can provide important information to predict the pathologic responses to the NAC. The pathologic appearance, grade, ER, PR and HER2 in breast carcinoma may change after NAC. It is necessary to examine the histologic type, grade and the expression of ER, PR and HER2 after NAC once more.     

12例肾上腺淋巴瘤的影像学表现分析

目的探讨肾上腺淋巴瘤的影像学特点。方法回顾性分析12例初诊未治、有完整影像学资料及病理结果的肾上腺淋巴瘤患者的临床表现、病理类型及影像学表现。结果 12例均为非霍奇金淋巴瘤（2例原发性,10例继发性）。10例继发性病例中8例为双侧肾上腺受侵,2例为单侧受侵;8例表现为肾上腺肿物,2例为肾上腺增厚。8例边界清楚。4例伴有坏死或囊变。无伴有出血、钙化、脂肪者。增强扫描强化程度低于静脉期肝实质。8例伴多脏器受侵。9例伴淋巴结肿大,受侵淋巴结主要分布于腹腔及腹膜后。其中3例行PET-CT检查,肾上腺病变均伴有明显摄取增高,中位SUVmax为24.5。2例原发病例均为双侧肾上腺受侵,肿物密度混杂,内见囊变、坏死,增强扫描静脉期强化程度均低于肝实质。结论肾上腺淋巴瘤CT表现具有一定特征,以双侧受侵、边界清楚的低血供肿物为多见。继发病例常伴有多脏器、多组淋巴结受累。PET-CT有助于肿瘤定性诊断和观察有无淋巴结及其他脏器受累。     

乳腺癌新辅助化疗组织学疗效评价研究

目的 探讨乳腺癌新辅助化疗后根治标本的组织学疗效评价标准.方法 收集2005年6月至2007年6月乳腺癌新辅助化疗154例档案,其中改良根治术139例,保乳手术15例.化疗结束后4周内实施乳腺根治术.按照Miller and Payne(MP)分级系统的标准规范进行取材、制片和按该系统组织学疗效评价标准进行分级评价,同时与既往应用的肿瘤治疗反应评价系统(既往评价系统)进行比较.对所有病例进行常规随访.应用SPSS 13.0软件进行统计学处理.结果 (1)154例手术标本所获得的组织学疗效评价信息:MP分级系统1级12例(7.8%)、2级33例(21.4%)、3级64例(41.6%)、4级31例(20.1%)、5级14例(9.1%);既往评价系统分别为轻度治疗反应51例(33.1%)、中度治疗反应71例(46.1%)、重度治疗反应32例(20.8%).MP分级系统与既往评价系统各组病例比例之间存在统计学相关(X2=186.660,P<0.01).(2)154例患者中147例获得随访信息(95.5%),随访时间16～38个月;其中14例出现术后复发、远处转移或死亡.MP分级系统5个级别组与患者生存状态均相关(X2=11.612,P=0.020),既往评价系统3个级别组与患者生存状态均无关(X2=0.881,P=0.644).结论 MP分级系统可以用于肿瘤化疗后的组织学疗效评价,与预后相关.     

Lynch综合征相关结直肠癌的遗传基因及分子病理筛查策略

Lynch综合征（Lynch syndrom）是结直肠癌中最常见的遗传性肿瘤综合征,约占全部大肠癌的2~3%。该病患者同时增加了罹患肠外及第二肿瘤的风险。现已证明,Lynch综合征是由于编码错配修复基因（mismatch repair,MMR）——MLH1,MSH2,MSH6和PMS2的种系突变、失活导致的一类显性遗传性疾病,近年发现EPCAM的突变与MSH2表达缺失相关。尽管有Amsterdan及Bethesda等临床诊断标准,利用分子遗传学检测在MMR基因中发现致病性胚系突变仍为目前诊断Lynch综合征的金标准。对于发病年龄小于70岁的结直肠癌患者,均应进行Lynch综合征的筛查。首先需进行微卫星不稳定性（microsatellites instability,MSI）检测,检测手段包括PCR扩增微卫星位点及免疫组化（IHC）检测,而后对相应的MMR基因进行胚系突变的检测以明确是否为Lynch综合征以及相应的致病位点。对于MLH1表达缺失患者需进行BRAF基因突变检测和（或）MLH1启动子区域甲基化检测以除外散发性结直肠癌。对于确诊的患者建议进行家系筛查并进行规律的监测和随访。     

四例结直肠少见类型的混合性腺神经内分泌癌（MANEC）病例报道

混合性腺神经内分泌癌（MANEC）是一类罕见肿瘤,由至少各占30%的腺癌和神经内分泌肿瘤组成。本文报道了4例少见类型的结直肠MANEC,其中一例由低级别神经内分泌肿瘤（G1）和高分化管状腺癌组成,另外三例由高级别神经内分泌肿瘤（G3）和中——低分化腺癌组成。从以上病例总结中发现,MANEC的神经内分泌肿瘤成分具有更强的侵袭力和淋巴结转移率,所以目前MANEC的分级应该根据不同肿瘤成分进行更加细化的分类。