Reduced expression of retinoblastoma (Rb) gene protein is related to cell proliferation and prognosis in transitional-cell bladder cancer

Archival biopsy specimens from transitional-cell bladder cancers (n=222) were analysed immunohistochemically for expression of retinoblastoma (Rb) gene protein. The intensity of staining for Rb protein and the fraction of positive nuclei were analysed and related to several other prognostic factors and survival. Six per cent of the tumours were totally negative for Rb protein and abnormal (weak) expression was found in 40% of cases. The fraction of positive nuclei and abnormal expression (weak) were highly significantly interrelated (P<0.0001). A low value for the fraction of Rb-protein-positive nuclei was related to a large fraction in S phase (P=0.001), high mitotic index (P=0.016) and overexpression of epidermal growth factor receptor (P=0.034) and p53 protein (P=0.019). A normal Rb protein expression pattern was related to low S-phase values (P=0.0001) whereas over-expression of p53 was related to high S-phase values (P=0.0077). Morphometrically measured nuclear atypia and the fraction of Rb-protein-positive nuclei were negatively correlated (P<0.05). In univariate survival analysis altered expression of Rb protein (P=0.07) and low frequency (≤50%) of Rb-protein-positive nuclei (P=0.0128) predicted a poor outcome. In a multivariate analysis, reduced expression of Rb protein had no independent prognostic value over T category, papillary status and the size of the S-phase fraction. The results show that tumour-suppressor genes Rb and p53 participate in the growth regulation of human bladder cancer cells in vivo and accordingly modify the prognosis.     

Expression of altered retinoblastoma protein inversely correlates with tumor invasion in gastric carcinoma

INTRODUCTION Cellular proliferation normally follows an orderly progression through the cell cycle, which is governed by protein complexes encoding various genes. Malignant transformation results from a series of genetic alterations that lead to aberrant …     

视网膜母细胞瘤中P~(53)蛋白的免疫组化研究

为探讨Ｐ５３基因与视网膜母细胞瘤（Ｒｂ）发病的关系,应用免疫组化法检测了４９例Ｒｂ患儿肿瘤组织　　　　　　中Ｐ５３基因蛋白的表达状况,并与正常视网膜组织进行对照。结果显示,正常视网膜及Ｒｂ组织中均无Ｐ５３阳性染　　　　　　色。提示Ｐ５３基因突变与人类原发性Ｒｂ的发病无关。     

Overexpression of pancreatitis-associated protein (PAP) in human pancreatic ductal adenocarcinoma

Pancreatitis-associated protein (PAP) is almost absent in normal pancreas, but is strongly induced in acute pancreatitis. PAP mRNA is also expressed in cancer cells, including pancreatic ductal adenocarcinoma. However, the clinicopathological significance of PAP in human pancreatic cancer is not clear. We examined PAP expression in pancreatic tissues from individuals with pancreatic ductal adenocarcinoma using immunohistochemistry. PAP was overexpressed in 79% (30 of 38) of pancreatic ductal adenocarcinoma, 19% (7 of 36) of chronic pancreatitis, and 29% (2 of 7) of mucinous cystadenoma. PAP was found in malignant ductular structures in pancreatic carcinomas as well as in benign proliferating ductules and acinar cells in chronic pancreatitis. It was not expressed in normal pancreas. The incidence of PAP overexpression was significantly higher in pancreatic cancer than in the other pancreatic diseases (P < 0.01). PAP overexpression was significantly correlated with nodal involvement, distant metastasis (P < 0.05), and short survival (P < 0.01) in pancreatic cancer. These results suggest that overexpression of PAP in human pancreatic ductal adenocarcinoma indicates tumor aggressiveness.     

胰腺癌p27kip1、视网膜母细胞瘤基因蛋白和增殖细胞核抗原表达及与临床病理关系的研究

目的　探讨细胞周期负性调控因子p2 7kip1,视网膜母细胞瘤 (Rb)基因蛋白和增殖细胞核抗原 (PC NA)在胰腺癌发生、发展中的作用。方法　应用免疫组织化学技术 (SP法 ) ,对 32例胰腺癌及癌旁组织中p2 7kip1、Rb蛋白和PCNA表达进行检测。结果　p2 7kip1蛋白阳性表达率在胰腺癌组织中为 5 6 2 5 %,显著低于癌旁胰腺组织 (84 37%) (P <0 0 5 ) ,并与胰腺癌组织分化程度及淋巴结转移相关 (P <0 0 5 ) ;Rb基因蛋白阳性表达率在胰腺癌组织中为 5 0 0 0 %,显著低于癌旁胰腺组织 (78 13%) (P <0 0 5 ) ;PCNA阳性表达率在胰腺癌组织中为 71 87%,显著高于癌旁胰腺组织 (4 3 75 %) (P <0 0 5 ) ,并与胰腺癌组织分化程度和淋巴结转移均相关(P <0 .0 5 )。结论　p2 7kip1、Rb基因蛋白和PCNA与胰腺癌发生、发展密切相关。     

贲门癌组织中sPLA2（Ⅱa）的表达

目的探讨河南贲门癌高发区贲门癌组织中sPLA2（Ⅱa）的表达。方法采用免疫组化卵白素-生物素-过氧化物酶复合物（ABC）法分析80例贲门癌组织和16例贲门癌旁肠化组织中sPLA2（Ⅱa）的表达情况：结果sPLA2（Ⅱa）在癌旁肠化组织中的表达高于贲门腺癌组织（75．0％US37．5％，P〈0．05），高、中、低分化贲门腺癌sPLA2（Ⅱa）阳性率分别为38、5％、27．6％、48．0％，三组表达率差异无统计学意义（P〉0．05）。结论sPLA2（Ⅱa）可能参与了贲门癌的癌变过程。     

Expression of fibroblast activation protein in human pancreatic adenocarcinoma and its clinicopathological significance

AIM: To examine fibroblast activation protein (FAP) expression in pancreatic ductal adenocarcinoma (PDAC) and to analyze its relationship with the clinicopathology of PDAC.METHODS: FAP expression was examined in 134 PDAC specimens by immunohistochemistry, and in four pancreatic cancer cell lines (SW1990, Miapaca-2, AsPC-1 and BxPC-3) by Western blotting assay. We also analyzed the association between FAP expression in PDAC cells and the clinicopathology of PDAC patients.RESULTS: The results showed that the FAP was ex-pressed in both stromal fibroblast cells (98/134, 73.1%) and carcinoma cells (102/134, 76.1%). All 4 pancreatic cancer cell lines expressed FAP protein at different levels. Protein bands corresponding to the proteolytically active 170-kDa seprase dimer and its 88-kDa seprase subunit were identified. Higher FAP expression in carcinoma cells was associated with tumor size (P < 0.001), fibrotic focus (P = 0.003), perineural invasion (P = 0.009) and worse clinical outcome (P = 0.0085).CONCLUSION: FAP is highly expressed in carcinoma cells and fibroblasts in PDAC tissues, and its expression is associated with desmoplasia and worse prognosis.     

良性前列腺增生和前列腺癌组织中雄激素受体的表达

目的　探讨雄激素受体 (AR)与良性前列腺增生 (BPH)和前列腺癌 (PCa)的关系。　方法　应用免疫组织化学技术检测 4 0例BPH、4 0例PCa患者及 2 0例正常前列腺组织 (正常对照组 )AR的表达。　结果　BPH组、PCa组、正常对照组AR表达的阳性率分别为 98%、5 3%、75 % ,相互比较差异均有显著性 (P <0 0 5 )。高分化癌、中分化癌、低分化癌的AR表达的阳性率分别为 6 7%、5 6 %、30 % ,高、中分化癌的AR表达的阳性率比低分化癌高 (P <0 0 5 )。早期前列腺癌的AR表达阳性率 (6 9% )比晚期前列腺癌 (4 2 % )高 (P <0 0 5 )。　结论　BPH组织中AR的表达高于正常前列腺组织 ,AR在BPH的发生、发展中起着重要作用 ;PCa组织中AR的表达低于正常前列腺组织。AR的表达与肿瘤分级、分期相关。     

贲门腺癌组织中RKIP、E-cadherin的表达变化及相关性

目的 观察Raf激酶抑制蛋白（RKIP）、上皮型钙黏蛋白（E-cadherin）在贲门腺癌组织中的表达变化,并探讨其相关性.方法 应用免疫组化SP法检测160例贲门腺癌组织及癌旁非肿瘤组织中RKIP、E-cadherin的蛋白表达情况,分析其表达与临床病理参数的关系以及两者表达的相关性.结果 RKIP和E-cadherin在贲门腺癌组织中表达明显低于癌旁组织（P均＜0.05）.RKIP和E-cadherin在高分化、中分化和低分化的贲门腺癌组织中的表达差异有统计学意义（P均＜0.01）,在有淋巴结转移的贲门腺癌组织中表达低于无淋巴结转移的组织（P均＜0.05）.RKIP和E-cadherin在贲门腺癌组织中的表达呈正相关（r=0.388,P＜0.05）.结论 RKIP和E-cadherin 在贲门腺癌组织中表达降低,且两者表达呈正相关.     

三重基序家族蛋白在肺腺癌患者中的表达及其诊断意义

目的探讨三重基序家族蛋白(TRIM72)在肺腺癌组织及外周血、胸腔积液中的表达。方法收集2017年8月至2018年2月广东医科大学附属医院确诊的肺腺癌患者80例,并以同时段20例健康体检者作为对照组。通过免疫组织化学方法进行TRIM72表达检测。采用TRIM72酶联免疫吸附试验试剂盒对外周血、胸腔积液进行检测,并分析临床数据。结果TRIM72主要表达于正常气道上皮细胞中,而在肺腺癌组织中几乎不表达。肺腺癌患者外周血TRIM72水平明显低于对照组(t=8.727,P<0.05),与癌胚抗原呈负相关性(r=-0.556,P<0.001)。癌性胸腔积液TRIM72水平明显低于炎性积液(t=10.09,P<0.05)。采用TRIM72、CEA、CA125等指标对肺腺癌诊断作受试者工作曲曲线下面积分别为0.827、0.746、0.651,cut-off值分别为110.629 ng/L、4.535μg/L、33.965 U/ml,TRIM72同时联合CEA及CA125曲线下面积可达0.934。结论TRIM72可能作为肺腺癌诊断的生物学标记物,与肺腺癌的发生、发展及预后相关。     

Cdc42，Rb基因在哈萨克族食管癌中的表达及其意义的研究

目的 研究Cdc42和Rb基因在哈萨克族食管癌组织中的表达.方法 采用逆转录多聚酶链反应技术检测Cdc42和Rb基因在20例食管癌组织及其相应癌旁组织中的表达.结果 Cdc42基因在20例癌组织中有15例表达阳性,占75%,20例癌旁组织中有11例表达,占55%,其中癌组织表达量明显高于癌旁组织的有7例,占35%.Rb基因在20例癌组织中有13例表达阳性,占65%,20例癌旁组织中有9例表达,占45%,其中癌组织表达量明显高于癌旁组织的有10例,占50%,癌旁组织表达量高于癌组织的有6例,占30%.结论 Cdc42基因表达的改变,提示它们所参与的细胞凋亡及细胞周期过程的变化在哈萨克族食管癌的发生、发展过程中起了一定的作用.抑癌基因Rb在哈萨克族食管癌的发生发展中与其在其他民族中的作用可能有所不同.     

胃腺癌组织P53,P63和P73蛋白表达的意义

目的:探讨P53,P63和P73蛋白表达与胃腺癌临床病理特征之间的关系．方法:用免疫组织化学技术,检测72例胃腺癌及其癌旁正常组织中P53,P63和P73蛋白表达情况．所有研究对象均为湖北地区汉族人．其中,癌肿位于胃远端(胃窦、胃角)51例,胃近端(胃底、胃体)21例;肠型GAC 44例、弥漫型28例;高分化腺癌20例、中分化腺癌29例、低分化和未分化腺癌23例;TNM分期:Ⅰ和Ⅱ期13例,Ⅲ和Ⅳ期59例．结果:胃腺癌组织中P53,P63和P73蛋白阳性表达率均明显高于正常组织(X2=4．72,P<0．05; X2=5．51,P<0．05;X2=9．75,P<0．01);胃窦／胃角腺癌与胃底／胃体腺癌组织P53蛋白表达率无显著差异(P>0．05);在弥漫型胃腺癌中的表达率明显高于肠型胃腺癌(X2=4．68,P<0．05);在低分化腺癌与高中分化腺癌之间以及Ⅲ,Ⅳ期腺癌与Ⅰ,Ⅱ期胃腺癌之间的表达率的差异均有显著性(X2=7．06,P<0．05;X2=3．95, P<0．05)．P63蛋白在低分化腺癌组织中表达率明显高于高中分化腺癌(X2=7．36,P<0．05);在胃窦／胃角腺癌与胃底／胃体腺癌之间、在弥漫型与肠型胃腺癌之间、在Ⅰ,Ⅱ期胃腺癌与Ⅲ,Ⅳ期腺癌之间均无显著差异．P73蛋白在Ⅰ,Ⅱ期胃腺癌组织中的阳性表达率明显低于Ⅲ,Ⅳ期腺癌(X2=4．14,P<0．05),在胃窦／胃角腺癌与胃底／胃体腺癌之间、在弥漫型与肠型胃腺癌之间、在高、中及低分化胃腺癌之间均无显著差异．在P53蛋白阳性与阴性表达的胃腺癌之间,P63和P73蛋白阳性表达率的差异无显著性．结论:P53,P63和P73过度表达与胃腺癌的发生相关联,但并无交互作用．     

CD151在胃腺癌和宫颈癌中的表达

目的 探讨CD151在胃腺癌和宫颈癌中的表达及其意义.方法 应用免疫组织化学方法检测CD151在正常胃黏膜和宫颈黏膜组织及胃腺癌和宫颈癌组织中的表达.结果 CD151在所有的胃腺癌(58/58,100.0％)和宫颈癌组织(55/55,100.0％)都表达,在绝大多数正常胃黏膜( 26/28,92.9％)和宫颈黏膜组织(23/24,95.8％)中也都表达.CD151在胃腺癌和宫颈癌中的细胞阳性率及表达量都要显著高于正常组织(P＜0.05).结论 CD151是细胞增殖的一个标记分子;CD151蛋白在宫颈癌中高表达,是宫颈癌治疗的一个潜在靶点.     

前列腺癌患者血清甲状旁腺相关蛋白测定的意义

目的观察前列腺癌患者血清甲状旁腺相关蛋白（ＰＴＨｒＰ）与病情及前列腺特异抗原（ＰＳＡ）的关系。方法采用免疫放射法（ＩＲＭＡ）和放射免疫法（ＲＩＡ）测定３１例前列腺癌患者血清ＰＴＨｒＰ、ＰＳＡ和钙离子，并以５０例前列腺增生症（ＢＰＨ）、５５例健康人和５７例其它恶性肿瘤患者作对照。结果前列腺癌组血清ＰＴＨｒＰ（４．６±４．４ｐｍｏｌ／Ｌ）和ＰＳＡ（８０．０±５２．６μｇ／Ｌ）明显高于ＢＰＨ和健康组（均为Ｐ＜０．０１）。３１例前列腺癌患者中１３例（４１．６％）血清ＰＴＨｒＰ增高，这１３例均属Ｄ期，其血清ＰＴＨｒＰ水平明显高于Ａ期（Ｐ＜０．０１）。２１例前列腺癌伴发高钙血症（ＨＨＭ）者血清ＰＴＨｒＰ与ＰＳＡ呈正相关关系（ｒ＝０．８２３，Ｐ＜０．００１）。ＢＰＨ组无１例血清ＰＴＨｒＰ增高。结论血清ＰＴＨｒＰ与前列腺癌的病程进展有关，其含量增高表明肿瘤已属晚期     

NOD样受体家族蛋白3在中老年子宫内膜样腺癌组织中的表达及意义

目的探讨NOD样受体家族蛋白3（NOD-like receptor protein, NLRP3）在中老年患者子宫内膜样腺癌组织中的表达及临床意义。 方法选取2017年1月至2019年12月在浙江医院和浙江省肿瘤医院行手术切除的子宫内膜样腺癌患者35例,以及同期因子宫脱垂行全子宫切除术患者12例。采用实时荧光定量PCR、免疫印迹、免疫组化等方法检测比较不同子宫内膜组织中NLRP3 mRNA和蛋白的表达水平。同时应用子宫内膜样腺癌细胞系ishikawa和HEC-1A行体外细胞试验,观察NLRP3对子宫内膜样腺癌细胞增殖、侵袭及迁移能力的影响。两组间的比较采用t检验。 结果免疫组化检测：NLRP3在子宫内膜样腺癌组织中的表达水平明显高于正常子宫内膜组织,而且随FIGO分期及病理分级的增高而增高。实时荧光定量PCR检测：子宫内膜样腺癌组织中NLRP3 mRNA和NLRP3蛋白的表达水平均显著高于正常子宫内膜组织（t=3.769、4.316,P<0.05）。蛋白质印迹法：子宫内膜样腺癌组织中NLRP3蛋白表达明显强于正常子宫内膜组织。体外细胞试验：NLRP3 mRNA和NLRP3蛋白在ishikawa细胞和HEC-1A细胞中均有表达,而且两者在HEC-1A细胞中的表达水平均明显高于ishikawa细胞（t=2.373、2.559,P<0.05）;利用siRNA沉默子宫内膜样腺癌ishikawa细胞和HEC-1A细胞的NLRP3后,从第3天开始其增殖能力明显受限,并持续至细胞增殖实验结束的第7天;Transwell实验：沉默NLRP3后ishikawa细胞和HEC-1A细胞的迁移和侵袭数量均明显下降（t=7.343、6.571,3.859、3.289;P<0.05）。 结论NLRP3的表达与子宫内膜样腺癌细胞的增殖、侵袭和迁移能力密切相关。     

Correlation between clinicopathology and expression of heat shock protein 70 and glucose-regulated protein 94 in human colonic adenocarcinoma

AIM: To investigate the correlation between clinicopathology and expression of heat shock protein 70 (HSP70) and glucose-regulated protein 94 (grp94) in human colonic carcinoma. METHODS: The expression of HSP70 and grp94 was studied in 80 human colonic cancers with or without metastasis as well as in their adjacent mucous membrane by way of immunohistochemistry and pathology photograph analysis. RESULTS: The expression of HSP70 and grp94 was significantly higher in cancer than that in adjacent mucous membrane (92.5%, 85.0% vs 56.3%, 42.5%, P<0.01). HSP70 and grp94 expressed higher in moderately- and poorly-differentiated colonic cancers than that in their adjacent tissues (93.7%, 87.5%; 100%, 90% vs56.3%, 42.5%;P<0.01). Dukes C and D stages of colonic cancers showed higher positive rates than Dukes A and B stage groups (97.1%, 91.2%; 100%, 90.9%; vs 80%, 70%; 78.6%, 71.4%; P<0.05). There were definite differences in HSP70 and grp94 expression between metastasis groups and non-metastasis groups (100% vs 75%, 100% CONCLUSION: The HSP70 and grp94 expression rates in colonic cancer groups are significantly higher than that in their adjacent mucous membrane. The HSP70 and grp94 expression in poorly-differentiated colonic cancers with metastasis is significantly higher than well-differentiated cancers without metastasis. The overexpression of HSP70 and grp94 can be used as diagnostic or prognostic markers for colonic cancer.     

Expression of erbB-3 protein in colorectal adenocarcinoma: correlation with poor survival

Background/aims: The family of erbB receptors includes four transmembrane glycoproteins with tyrosine kinase activity. These receptors are widely expressed in normal tissues, but they also have been implicated in the development of several human adenocarcinomas. c-erbB-3/HER-3 has been detected to a greater or lesser extent in many tissues from the digestive, urinary, reproductive and respiratory tracts. The overexpression of c-erbB-3/HER-3 protein has also been shown in 53%–88% of colorectal adenocarcinomas. In this study we investigated the expression of the c-erbB-3/HER-3 gene product in colorectal tumour samples, and compared the results obtained with several clinicopathological parameters, including the survival of patients. Methods: Paraffin-embedded tissue sections were analysed immunohistochemically, using monoclonal antibody RTJ1 to human erbB-3 protein. Antibody RTJ1 specificity was confirmed by immunoprecipitation followed by Western blotting analysis. Amplification of the erbB-3 oncogene was tested by dot-blot hybridization. Results: Adenocarcinomas of the colon were positive for erbB-3 protein in 78% of samples examined. Dot-blot analysis showed no amplification of the erbB-3 gene in colon adenocarcinomas. Statistical analysis showed that patients with tumours that could not be stained for erbB-3 protein survived significantly longer (P < 0.05) than patients with tumours staining positive for the erbB-3 protein. A Cox proportional-hazards model with stepwise variable selection identified age, sex and erbB-3 expression as important prognostic factors. Conclusion: These findings demonstrate that erbB-3 protein expression could serve as a prognostic factor in colorectal malignancies. Received: 7 August 1999 / Accepted: 8 November 1999     

The occurrence of prion protein in surgically resected pancreatic adenocarcinoma

Background: Among the several new targets for the comprehension of the biology of pancreatic ductal adenocarcinoma (PDAC), Prion proteins (PrPc) deserve particular mention, since they share a marked neurotropism. Actually, PrPc could have also a role in tumorigenesis, as recently demonstrated. However, only few in vitro studies in cell cultures showed the occurrence of PrPc in PDAC cells. We aim to evaluate the presence of PrPc in vivo in PDAC tissues as a potential new biomarker.MethodsSamples from tumors of 23 patients undergone pancreatic resections from July 2018 to May 2020 at our institution were collected and analyzed. Immunohistochemistry and western blotting of PDAC tissues were compared with control tissues. Immunohistochemistry was used also to evaluate the localization of PrPc and of CD155, a tumoral stem-cell marker.ResultsAll cases were moderately differentiated PDAC, with perineural invasion (PNI) in 19/23 cases (83%). According to western-blot analysis, PrPc was markedly expressed in PDAC tissues (273.5 ± 44.63 OD) respect to controls (100 ± 28.35 OD, p = 0.0018). Immunohistochemistry confirmed these findings, with higher linear staining of PrPc in PDAC ducts (127.145 ± 7.56 μm vs 75.21 ± 5.01 μm, p < 0.0001). PrPc and CD155 exactly overlapped in ductal tumoral cells, highlighting the possible relationship of PrPc with cancer stemness. Finally, PrPc expression related with cancer stage and there was a potential correspondence with PNI.ConclusionsOur work provides evidence for increased levels of PrPc in PDAC. This might contribute to cancer aggressiveness and provides a potentially new biomarker. Work is in progress to decipher clinical implications.     

视网膜母细胞瘤中P^53蛋白的免疫组化研究

为探讨P^53基因与视网膜母细胞瘤（Rb）发病的关系,应用免疫组化法检测了49例Rb患儿肿瘤组织中P^53基因蛋白的表达状况,并与正常视网膜组织进行对照。结果显示,正常视网膜及Rb组织中均无P^53阳性染色。提示P^53基因突变与人类原发性Rb的发病无关。