胆囊良恶性病变组织中HMGA2和CD9表达及意义

目的 研究胆囊良恶性病变组织中HMGA2和CD9表达水平及其临床病理意义.方法 108例胆囊腺癌、46例癌旁组织、15例腺瘤和35例慢性胆囊炎手术切除标本常规制作石蜡包埋切片, HMGA2和CD9染色方法为EnVision免疫组化法.结果 胆囊腺癌HMGA2表达阳性率明显高于癌旁组织(χ2=16.13,P<0.01)、腺瘤性息肉(χ2=8.19,P<0.01)和慢性胆囊炎(χ2=21.41,P<0.01); 胆囊腺癌CD9表达阳性率明显低于癌旁组织(χ2=8.76,P<0.01)、腺瘤性息肉(χ2=3.96,P<0.05)和慢性胆囊炎(χ2=14.31,P<0.01);HMGA2表达阳性和(或)CD9表达阴性的良性病例的胆囊上皮均呈中至重度不典型增生.高分化、肿块最大径<2 cm、无淋巴结转移、未侵犯周围组织的病例HMGA2表达阳性率明显低于低分化、肿块最大径≥2 cm、淋巴结转移和侵犯周围组织的病例(P<0.05或P<0.01);高分化腺癌、肿块最大径<2 cm、无淋巴结转移和未侵犯周围组织的病例CD9表达阳性率明显高于低分化腺癌、肿块最大径≥2 cm、淋巴结转移和侵犯周围组织病例(P<0.05或P<0.01).经Kaplan-Meier生存分析发现HMGA2表达阳性病例术后生存期明显低于阴性表达病例(P=0.020),但CD9表达阳性病例术后生存期明显高于阴性表达病例(P=0.019);Cox多变量回归分析显示HMGA2阳性表达和(或)CD9表达阴性是反映胆囊腺癌预后不良的一个重要指标.结论 HMGA2和CD9表达与胆囊腺癌发生、临床生物学行为及预后有密切关系.     

膀胱移行细胞癌中E2F3的表达及意义

目的探讨E2F3在膀胱移行细胞癌中的表达及临床意义。方法采用lit-PCR和免疫组化技术检测32例膀胱移行细胞癌及14例正常膀胱移行上皮组织中E2F3 mRNA及蛋白的表达。结果膀胱移行细胞癌中E2F3m RNA及蛋白的表达明显高于正常膀胱移行上皮组织（P〈0．05）,E2F3 mRNA及蛋白的表达随肿瘤分级、分期增高而相应增高（P〈0．05）。结论E2F3对膀胱移行细胞癌的发生发展发挥重要的作用,并可在一定程度上反映肿瘤的恶性程度。     

B细胞淋巴瘤中E2F1、BIRC5、PLK1蛋白表达及其临床意义

目的探讨E2F1、BIRC5、PLK1蛋白在B细胞淋巴瘤中的表达及其临床意义。方法收集80例B细胞淋巴瘤及30例反应性增生淋巴组织,用免疫组化SP法检测两组中E2F1、BIRC5、PLK1的表达差异。结果 B细胞淋巴瘤中E2F1、BIRC5、PLK1蛋白表达均明显高于反应性增生组(P<0.05),与临床分期密切相关(P<0.01),与年龄、发生部位无关(P>0.05)。E2F1、PLK1蛋白表达与组织学亚型及恶性程度相关(P<0.05),BIRC5表达与此二者无关(P>0.05)。E2F1在男性患者中的表达高于女性患者(P<0.01),BIRC5、PLK1蛋白在不同性别组中的表达差异无显著性(P>0.05)。经Spearman等级相关分析发现E2F1、BIRC5、PLK1蛋白在B细胞淋巴瘤中的表达均呈正相关(P<0.01)。结论联合检测E2F1、BIRC5、PLK1对B细胞淋巴瘤的诊断、治疗及预后判断具有一定的现实意义。     

宫颈鳞状细胞癌和癌前病变中Skp2表达及其与HPV16/18感染的关系

目的 探讨skp2在宫颈鳞状细胞癌和癌前病变中的表达规律及其与人乳头状瘤病毒(HPV)感染之间的关系.方法 采用免疫组织化学(ABC法)和原位杂交检测Skp2蛋白和HPV16/18 DNA在30例正常宫颈鳞状上皮、29例宫颈低级别上皮内瘤变、31例高级别上皮内瘤变和31例宫颈鳞状细胞癌中的表达.结果 Skp2在正常宫颈鳞状上皮中呈阴性,与宫颈低级别上皮内瘤变(阳性表达率为13.8%,4/29)之间差异无统计学意义(P>0.05).随着上皮病变级别升高,表达也逐渐增强,在宫颈鳞状细胞癌中表达更强;HPV16/18 DNA在四组中的阳性表达率,除高级别上皮内瘤变和宫颈鳞状细胞癌两组间差异无统计学意义外(均为96.8%),其余各组之间差异均有统计学意义(P<0.01);在宫颈低级别上皮内瘤变中skp2蛋白表达和HPV感染相关无统计学意义,但在高级别上皮内瘤变和宫颈鳞状细胞癌两组中均呈正相关(γ高级别=0.373,γ癌 =0.416,P<0.05).结论 Skp2过表达主要在宫颈鳞状细胞癌形成的中晚期起作用,可作为一个早期诊断恶性的指标,且可能与HPV16/18感染有协同作用.E7-skp2-Rb可能是HPV感染诱导宫颈鳞状细胞癌形成的一条新致癌途径.     

乳腺癌中E-cadherin的表达及其临床病理意义

目的 探讨上皮钙黏附表（E-cadherin，E-cad）与乳腺癌临床病理和生物学行为的关系。方法 用免疫组化S-P法检测乳腺浸润性导管癌和浸润性小叶癌中E-cad的表达情况及其与淋巴结转移，ER-PR表达水平的相关性。结果 乳腺浸润性导管癌E-cad表达高于浸润性小叶瘤，有淋巴结转移者E-cad表达低于无转移者，E-cad高表达的乳腺浸润性导管癌及浸润性小肾癌中均与ER-PR表达水平成正相关。结论 E-cad中作为乳腺癌分类、转移潜能和预后判断的参考指标。     

结直肠癌中ZHX2蛋白表达的检测及其临床病理意义

目的检测结直肠癌中ZHX2蛋白的表达情况,探讨ZHX2与结直肠癌的关系。方法利用免疫组化法分别检测73例结直肠癌组织及其对应的癌旁正常组织中的ZHX2蛋白的表达情况。结果 73例结直肠癌组织中ZHX2蛋白的阳性率为82.2%(60/73),癌旁正常组织中ZHX2蛋白的阳性率为94.5%(69/73),差异具有统计学意义(P<0.05)。在结直肠癌组织中,ZHX2蛋白的阳性表达与肿瘤的发生部位及分化程度有关(P<0.05),与性别、年龄、肿瘤大小、浸润深度、淋巴结转移及Dukes分期无关(P>0.05)。ZHX2(+)组患者的生存时间长于ZHX2(-)组(P<0.05)。结论 ZHX2作为一种转录抑制因子,可能参与结直肠癌的发生与演进,并有助于患者预后的判断。     

乳腺癌中p27和c-erbB-2的表达及意义

目的　探讨乳腺癌中 p2 7和c erbB 2表达情况和意义。 方法　用免疫组化S P法检测 4 0例乳腺癌中 p2 7和c erbB 2的表达。结果　正常乳腺组织c erbB 2表达阴性 ,癌组织中阳性率为 37 5 % (15 / 4 0 ) ,两者差异有显著性 (P <0 0 0 1)。 4 0例乳腺癌组织中 p2 7高表达率为 32 5 % (13/ 4 0 ) ,正常乳腺组织高表达为 80 % ,两者差异有显著性 (P <0 0 0 1)。p2 7高表达与癌组织分化、淋巴结转移和复发有关 (P <0 0 5 )。结论　基因p2 7和c erbB 2表达异常是乳腺癌产生的机制之一 ,与乳腺癌的发生及发展有关。p2 7可能是乳腺癌的一个重要预后指标     

胆囊良恶性疾病组织中癌干细胞抗原表达及其意义

前列腺干细胞抗原（prostate stem cell antigen,PSCA）和Oct-4干细胞抗原均为癌干细胞特异性标记物,其表达水平与恶性肿瘤发生、进展及预后等密切相关。我们应用免疫组织化学EnVision法研究胆囊腺癌、癌旁组织和慢性胆囊炎组织中PSCA和Oct-4表达水平及其临床病理意义。     

三阴性乳腺癌中DBC2的表达及其临床病理意义

目的探讨乳腺癌缺失基因2(deleted in breast cancer2,DBC2)在三阴性乳腺癌(triple-negative breast cancer,TNBC)中的表达,分析其临床病理学意义。方法收集195例乳腺癌标本,采用免疫组化SP法检测38例TNBC、50例非三阴性乳腺癌(non-triple negative breast cancer,NTNBC)和30例正常乳腺组织中DBC2的表达;应用荧光原位杂交技术(fluorescent in situ hybridization,FISH)检测38例TNBC中HER-2基因扩增。结果正常乳腺组织中仅2例DBC2表达缺失(2/30),NTNBC组中21例DBC2表达缺失(21/50);TNBC组中19例DBC2表达缺失(19/38),其表达缺失率高于NTNBC组和正常乳腺组。结论 TNBC中DBC2表达明显缺失,其与肿瘤的增殖和高侵袭性相关,有望成为TNBC靶向治疗的潜在靶点。     

诱导型NOS与p53、Bax蛋白在胆囊良恶性病变中的表达及相关意义

目的　探讨诱导型一氧化氮合酶 (iNOS)与凋亡诱导基因p5 3、Bax蛋白在胆囊良恶性病变中的表达及相关意义。　方法　采用免疫组织化学SP法检测iNOS及p5 3、Bax蛋白在 16例慢性胆囊炎、11例慢性胆囊炎伴胆囊腺肌瘤增生及 2 4例胆囊腺癌中的表达。　结果　 1 在胆囊良恶性病变的胆囊壁中均有iNOS、Bax表达 ,在胆囊腺癌中iNOS、Bax表达下降 (P <0 0 5 ) ,p5 3仅在部分胆囊腺癌细胞核中有较强阳性表达 ;2 在胆囊良恶性病变中 ,iNOS与Bax表达呈正相关 (P <0 0 1) ,p5 3与Bax表达呈负相关 (P <0 0 1)。　结论　慢性胆囊炎尤其是慢性胆囊炎伴腺肌瘤增生是胆囊腺癌重要的危险因素 ,NO是重要中介分子 ,NO诱导胆囊良性病变恶变的作用与细胞凋亡有密切关系。     

Immunohistochemical expression of cyclin D1, E2F-1, and Ki-67 in benign and malignant thyroid lesions

Cyclin D1 and E2F-1 proteins are essential for the regulation of the G1/S transition through the cell cycle. Cyclin D1, a product of the bcl-1 gene, phosphorylates the retinoblastoma protein, releasing E2F-1, which in turn activates genes involved in DNA synthesis. Expression patterns of E2F-1 protein in thyroid proliferations have not been reported. This study used monoclonal antibodies for cyclin D1 and E2F-1 proteins to immunostain sections of normal thyroid, hyperplastic (cellular) nodules, follicular adenomas, follicular carcinomas, and papillary carcinomas. The proliferation rate was examined using an antibody specific for the Ki-67 antigen. Fluorescence in situ hybridization (FISH) methods and chromosome 11-specific probes were also employed to determine chromosome copy number and to assess for evidence of amplification at the 11q13 locus in papillary and follicular carcinomas with cyclin D1 overexpression. Concurrent overexpression of Ki-67, cyclin D1, and E2F-1 was found in the majority of benign and malignant thyroid lesions, compared with normal thyroid tissue. Cyclin D1 up-regulation was not due to extra copies of chromosome 11, or bcl-1 gene amplification. Malignant tumours showed the highest expression for all three markers, particularly papillary carcinomas. E2F-1 was detected at the same or slightly lower levels than cyclin D1. It was only found when cyclin D1 was overexpressed. Because cyclin D1 normally activates E2F-1, up-regulation of cyclin D1 may lead to E2F-1 overexpression in benign and malignant thyroid lesions.     

Expression of heat-shock protein gp96 in gallbladder cancer and its prognostic clinical significance

Purpose: To detect the expression and prognostic clinical significance of heat-shock protein gp96 (HSP gp96) in gallbladder cancer. Methods: Immunohistochemistry was used to detect and compare the rate of HSP gp96 expression in 107 samples of gallbladder cancer, 70 of gallbladder adenoma and 67 of chronic cholecystitis. The association of clinicopathological factors and patients’ survival were calculated by univariate and multivariate (Cox proportional hazard regression method) analysis. Results: The expression positive rate of HSP gp96 was 90.7% (97/107) in gallbladder cancer, 71.4% (50/70) in gallbladder adenoma and 47.76% (32/67) in chronic cholecystitis respectively. The positive rate of HSP gp96 in gallbladder cancer tissues was significantly higher than that in gallbladder adenoma and chronic cholecystitis tissues (P < 0.01). Multivariate and Cox regression analysis showed that positive of HSP gp96 (P = 0.026) expression was an independent poor prognostic predictor in gallbladder cancer. Conclusions: HSP gp96-positive expression is closely correlated with poor survival in gallbladder cancer.     

Clinicopathologic significance of minichromosome maintenance protein 2 and Tat-interacting protein 30 expression in benign and malignant lesions of the gallbladder

Gallbladder cancers are aggressive tumors with a poor prognosis and high mortality rate. To find specific biological markers for early diagnosis and prognosis and to develop possible alternative treatment strategies, we examined minichromosome maintenance protein 2 (MCM2) and Tat-interacting protein 30 (TIP30) expression in 108 gallbladder adenocarcinomas, 15 gallbladder polyps, 35 chronic cholecystitis tissues, and 46 peritumoral tissues using immunohistochemistry. Expression of MCM2 was significantly higher in adenocarcinomas than in peritumoral tissues (χ2 = 8.41; P < .01), adenomatous polyps (χ2 = 6.81; P < .01), and chronic cholecystitis (χ2 = 21.00; P < .01). In contrast, Tat-interacting protein 30 expression was significantly less in adenocarcinomas than in peritumoral tissues (χ2 = 13.26; P < .01), adenomatous polyps (χ2 = 4.76; P < .05), and chronic cholecystitis (χ2 = 18.93; P < .01). The benign lesions in gallbladder epithelium with positive MCM2 or negative Tat-interacting protein 30 expression showed moderate to severe atypical hyperplasia. Expression of MCM2 and absence of Tat-interacting protein 30 were significantly associated with poor differentiation, large tumor mass, lymph node metastasis, and invasion of adenocarcinoma. Univariate Kaplan-Meier analysis showed that either elevated MCM2 (P = .006) or lowered Tat-interacting protein 30 (P = .006) expression was closely associated with shorter overall survival. Multivariate Cox regression analysis revealed that expression of MCM2 (P = .007) or nonexpression of Tat-interacting protein 30 (P = .009) was an independent predictor of a poor prognosis in adenocarcinoma. Our results suggest that overexpression of MCM2 or loss of expression of Tat-interacting protein 30 is closely related to carcinogenesis, progression, biological behavior, and prognosis of gallbladder adenocarcinoma.     

High DBC1 (CCAR2) expression in gallbladder carcinoma is associated with favorable clinicopathological factors

There have been several studies on gallbladder carcinogenesis, and mutations of the KRAS, TP53, and CDKN2A genes have been reported in gallbladder carcinoma. The DBC1 gene (deleted in breast cancer 1) was initially cloned from region 8p21, which was homozygously deleted in breast cancer. DBC1 has been implicated in cancer cell proliferation and death. The functional role of DBC1 in normal cells and the role of DBC1 loss in cancer are not entirely clear. And DBC1 expression and its clinical implications in gallbladder carcinoma have yet to be thoroughly elucidated. Therefore, we evaluated DBC1 expression in 104 gallbladder carcinoma tissues in relation to survival and other prognostic factors via immunohistochemical analysis. DBC1 expression was divided into two categories: high DBC1 expression was observed in 32/104 cases (30.8%) and low expression in 72/104 cases (69.2%). High DBC1 expression correlated significantly with favorable clinicopathologic variables. Furthermore, in survival analysis, the high-DBC1 expression group showed a better survival rate compared to the low-DBC1 expression group. In conclusion, high DBC1 expression is associated with several favorable clinicopathologic factors in gallbladder carcinoma. These findings suggest that loss of DBC1 expression plays a role in tumorigenesis and tumor progression in gallbladder carcinoma.     

Lipid profiling of cancerous and benign gallbladder tissues by (1) H NMR spectroscopy

Qualitative and quantitative ¹H NMR analysis of lipid extracts of gallbladder tissue in chronic cholecystitis (CC, benign) (n = 14), xanthogranulomatous cholecystitis (XGC, intermediate) (n = 9) and gallbladder cancer (GBC, malignant) (n = 8) was carried out to understand the mechanisms involved in the transformation of benign gallbladder tissue to intermediate and malignant tissue. The results revealed alterations in various tissue lipid components in gallbladder in CC, XGC and GBC. The difference in the nature of lipid components in benign and malignant disease may aid in the identification of the biological pathways involved in the etiopathogenesis of GBC. This is the first study on lipid profiling of gallbladder tissue by ¹H NMR spectroscopy, and has possible implications for the development of future diagnostic approaches. Copyright © 2010 John Wiley & Sons, Ltd.     

膀胱尿路上皮癌中PD-L1和PD-L2的表达及临床意义

目的 探讨膀胱尿路上皮癌(urothelial bladder cancer,UBC)中程序性死亡配体-1(programmed death-ligand 1,PD-L1)以及程序性死亡配体-2(programmed death-ligand 2,PD-L2)的表达及临床意义.方法 采用免疫组化法检测58例UBC组织中...     

E-Cadherin在乳腺癌中的表达及其意义

目的：探讨Ｅ－Ｃａｄｈｅｒｉｎ表达与乳腺癌的分级、浸润，淋巴结转移及病人后的关系。方法．：采用免疫组化Ｓ－Ｐ方法对１０９例乳ａｄｈｅｒｉｎ表达进行研究。结果：乳腺癌Ｅ－Ｃａｄｈｅｒｉｎ表达阳笥纺为５２．３％，，其表达与肿瘤组织学类型无关。Ｅ－Ｃａｄｈｅｒｉｎ表达，阴性患者淋巴结转移率显著高于阳性者；Ｅ－Ｃａｄｈｅｒｉｎ阳性患者５年生存率比阳性者显著增高。结论：Ｅ－Ｃａｄｈｅｒｉｎ表达对估计乳腺癌淋     

Type 1 protein tyrosine kinases in benign and malignant breast lesions

Aims : To determine their significance, we examined the expression pattern of the four epidermal growth factor receptor (EGFR) family members as well as the phosphotyrosine kinase activity in breast tumour tissues.  

Methods and results

Fifty-three malignant breast tumours, four breast cancer cell lines, and 10 benign breast tumours were investigated. Fifty-three per cent (28/53) of the malignant tumours expressed EGFR protein, and the majority of these positive tumours were strongly positive. Eighty per cent (8/10) of the benign tumours also expressed EGFR protein, but all in a lower or moderate level. An association between EGFR expression and increasing malignancy grade was found in the group of infiltrating ductal carcinomas. Of the malignant tumours, 35.8% (19/53) expressed c-erbB-2 protein and 17% (9/53) c-erbB-3 protein, while no expression of c-erbB-2 and c-erbB-3 proteins was found in the benign tumours. Contrary to previous reports, we observed c-erbB-4 receptor protein to be less expressed in the malignant breast tumours. The 'normal' breast epithelial cells adjacent to the malignant tumours and the benign tumours demonstrated intensified membrane staining for c-erbB-4, while a number of the malignant tumours demonstrated a weak cytoplasmic staining or were negative. However, several malignant tumours with strong membrane staining for the c-erbB-4 protein were also found. No simple association between the expression of the four receptors and phosphotyrosine kinase activity was found.  

Conclusion

Our study has revealed a complex expression pattern of the EGFR family members in breast tumour cells. While the data about EGFR, c-erbB-2, c-erbB-3 and phosphotyrosine are largely in line with what has been reported, we found the c-erbB-4 protein expression to be decreased in the malignant tumours.