结肠良,恶性病变中细胞凋亡及其与bcl—2,bax,PCNA蛋白表达？…

目的：了解结肠良、恶性变中细胞凋亡与增殖,及其与相关基因蛋白的表达及其生物学意义。方法应用免疫组织化学Ｓ－Ｐ法检测１４８例结肠良、恶性病变标本中ｂｃｌ－２、ｂａｘ和ＰＣＮＡ蛋白的表达,并对其中７５例标本进行凋亡指数（ＡＩ）和有丝分裂指数（ＭＩ）测定。结果ＰＣＮＡ与ＡＩ和ＭＩ密切相关（Ｐ〈０．０１）;而ｂｃｌ－２和ｂａｘ仅与ＡＩ有关（Ｐ〈０．０１）;ｂｃｌ－２和ＰＣＮＡ蛋白在结肠腺癌和腺瘤中表达率显     

鼻咽癌组织中bcl—2蛋白和增殖细胞核抗原的表达及意义

应用免疫组化ＳＰ法研究４１例鼻咽癌组织中ｂｃｌ－２蛋白和增殖细胞核抗原（ＰＣＮＡ）的表达及意义。结果显示ｂｃｌ－２蛋白在鼻咽癌中出现异常高表达（阳性率为８２．９％），ｂｃｌ－２表达与组织学分级及颈淋巴结转移无显著性关系（Ｐ＞０．０５）；ＰＣＮＡ表达随肿瘤分级升高而增高，且与淋巴结转移有关。结果表明ｂｃｌ－２基因对鼻咽上皮的良恶性诊断具有重要的参考价值，ＰＣＮＡ可作为鼻咽癌恶性程度及预后判定的指标之一，同时发现ｂｃｌ－２蛋白与ＰＣＮＡ表达间无相关。     

鼻咽癌组织中bcl—2及EB病毒潜伏膜蛋白表达与放射诱发细胞？…

目的：探讨鼻咽癌（ＮＰＣ）组织ｂｃｌ－２及ＥＢ病毒潜伏膜蛋白（ＬＭＰ）表达与放射诱发细胞凋亡的关系。方法采用免疫组化Ｓ－Ｐ法及ＴｄＴ酶介导的生物素化ｄＵＴＰ缺口要端标记技术（ＴＵＮＥＬ法）,分别检测３５例ＮＰＣ组中ｂｃｌ－２及ＥＢ病毒ＬＭＰ的表达,以及放疗总量为１０Ｇｙ时ＮＰＣ组织的细胞凋亡率（ＡＲ）。结果ＮＰＣ组织ｂｃｌ－２及ＬＭＰ的表达率分别为７１．４％（２５／３５）、４５．７％（１６／３５）     

大肠腺癌中p16、bcl-2异常表达与多药耐药性关系的研究

目的　研究大肠腺癌ｐ１６、ｂｃｌ－２ 表达与多药耐药性的关系。方法　应用Ｓ－Ｐ免疫组化法检测５２例大肠腺癌及３０例癌旁组织中ｐ１６、ｂｃｌ－２、ｐ－ｇｐ 的表达。结果　癌组织中ｐ１６ 阳性率 ６１．５％ （３２／５２）;ｂｃｌ－２ 阳性率７８．８％ （４１／５２）;ｐ－ｇｐ 阳性率８２．６％ （４３／５２）。ｐ１６ 在不典型增生组织的表达高于正常粘膜上皮（Ｐ＜ ０．０５）,癌与不典型增生组织的表达无差异（Ｐ＞ ０．０５）。癌ｐ１６ 表达水平与癌组织分化呈正相关,与肿瘤细胞的浸润深度、淋巴结转移及ｐ－ｇｐ 表达水平呈负相关。ｂｃｌ－２ 在癌旁的正常粘膜上皮无表达,在癌与不典型增生及ｐ－ｇｐ 的表达无差异（Ｐ＞ ０．０５）。ｐ－ｇｐ 在癌旁与癌的表达无差异（Ｐ＞ ０．０５）,与肿瘤的浸润深度及淋巴结转移呈正相关。结论　ｐ１６,ｂｃｌ－２,ｍ ｄｒ－１基因表达对判断病人耐药程度、设计治疗方案、判断预后具有重要的临床意义     

胃癌组织bcl—2蛋白表达和微卫星不稳定性研究及其临床意义

目的：研究ｂｃｌ－２蛋白过度表达和染色体１８ｑ微卫星不稳定性（ＭＳＩ）在胃癌发生及发展过程中的作用。方法：采用ＰＣＲ为基础的方法和免疫组织化学技术检测５０例手术切除胃癌标本的微卫星不稳定性及ｂｃｌ－２蛋白表达。结果：胃癌ｂｃｌ－２蛋白表达阳性率为６０％（３０／５０）；ＭＳＩ检出率为３０％（１５／５０）；中～高分化腺癌ＭＳＩ发生率（５３．３％，８／１５）显著高于低分化腺癌（１６．２％，５／３１）（Ｐ＜０．０５）。ｂｃｌ－２蛋白表达与ＭＳＩ无显著相关。结论：ｂｃｌ－２蛋白过度表达及ＭＳＩ（１８ｑ）在胃癌的发生中均发挥重要作用，二者引起胃癌发生机制有所不同     

P-糖蛋白、bcl-2蛋白和增殖细胞核抗原在肺癌组织中的表达及意义

目的：研究Ｐ－糖蛋白（Ｐ－ｇｌｙｃｏｐｒｏｔｅｉｎ,Ｐ－ｇｐ）的表达与ｂｃｌ－２蛋白和增殖细胞核抗原（ｐｒｏｌｏｆｅｒａｔｉｎｇ－ｃｅｌｌｎｕｃｌｅａｒ ａｎｔｉｇｅｎ,ＰＣＮＡ）表达的关系及意义。方法：用特异性鼠抗人单克隆抗体,用ＳＰ免疫组织化学方法检测石蜡包埋的肺癌标本中Ｐ－ｇｐ,ｂｃｌ－２蛋白和ＰＣＮＡ的表达,结果：在小细胞肺癌（ｓａｍｌｌ ｃｅｌｌ ｌｕｎｇ ｃａｎｃｅｒ,ＳＣＬＣ）中,Ｐ     

骨肉瘤细胞凋亡与p53和bcl-2表达的关系

目的：探讨骨肉瘤细胞凋亡的和５３、ｂｃｌ－２表达及细胞增殖的相关性,及其对患者预后的影响。方法：在８０例骨肉瘤标本中,用ＤＮＡ末端标记方法检测细胞凋亡,免疫组化检测Ｐ５３、ｂｃｌ－２和增殖细胞核怕的表达。结果：８０例骨肉瘤中凋亡指数范围为０．６３￣１８．８％,Ｐ５３和ｂｃｌ－２蛋白检出率分别为３７．５％和６０％,ＰＣＮＡ指数范围为１２￣９６％。统计学分析表明,细胞凋亡与Ｐ５３、ＰＣＮＡ表达呈正相关     

肝癌组织中bcl—2和bax蛋白表达及与PCNA表达的关系

目的探讨ｂｃｌ－２和ｂａｘ与肝癌发生的关系。方法用免疫组化方法研究３４例肝癌组织中ｂｃｌ－２和ｂａｘ的表达及与ＰＣＮＡ的关系。结果显示３４例肝细胞癌中５例ｂｃｌ－２阳性,阳性率为１４．７％,８例癌旁组织阳性,阳性率为２３．５％。７例ｂａｘ阳性,阳性率为２０．６％,癌旁组织２２例阳性,阳性率为６４．７％。ｂｃｌ－２和ｂａｘ表达与ＰＣ－ＮＡ增殖指数间无明显关系（Ｐ＞０．０５）。结论ｂｃｌ－２和ｂａｘ的变化可能影响肝细胞的凋亡状态,在肝癌发生中可能起一定作用,而并不引起细胞的增殖。     

甲状腺肿瘤组织CD15抗原和bcl—2基因蛋白表达的临床意义

目的：研究甲状腺癌组织中ＣＤ１５抗原和ｂｃｌ－２的基因蛋白的表达与肿瘤发生和转移的关系,并探讨ＣＤ１５与ｂｃｌ－２基因蛋白表达的关系。方法：应用微波－ＬＳＡＢ免疫组织化学法检测５０例甲状腺癌、４５例甲状腺腺瘤和２０例癌旁正常甲状腺组织中ＣＤ１５和ｂｃｌ－２基因蛋白表达。结果：在甲状腺癌中ＣＤ１５和ｂｃｌ－２基因蛋白表达阳性率分别为６８．０％和４６．０％,均显著高于甲状腺腺癌和癌旁正常甲状腺组织（Ｐ     

宫颈腺癌c—erbB—2增殖细胞核抗原表达及其意义

探讨宫颈腺癌组织中ｃ－ｅｒｂＢ－２、增殖细胞核抗原（ＰＣＮＡ）表达的意义。方法采用免疫组化方法检测７４例宫颈腺癌组织ｃ－ｅｒｂＢ－２及ＰＣＮＡ的表达。结果ｃ－ｅｒｂＢ－２阳性表达率为４５．９％,阳性表达组盆腔淋巴结转移率（５７．１％）高于阴性组（２４．０％）,Ｐ＝０．０４１;５年生存率（３２．４％）低于阴性组（５８．９％）,Ｐ＝０．００８。全组ＰＣＮＡ平均标记指数为（４０．６±２０．１）％（０．１％～９１．４％）。淋巴结转移组平均ＰＣＮＡ标记指数（５６．４％）高于阴性组（３８．５％）,Ｐ＝０．０１６。ＰＣＮＡ指数＜４０％组预后较好,ｃ－ｅｒｂＢ－２阳性表达者ＰＣＮＡ标记指数值较高,为４４．７％,阴性表达者为３４．６％,Ｐ＝０．００３。结论ｃ－ｅｒｂＢ－２、ＰＣＮＡ表达状况与宫颈腺癌生物学行为有关,可作为判断预后的参考指标。     

Evidence of reciprocity of bcl-2 and p53 expression in human colorectal adenomas and carcinomas.

Evidence of accumulating for the failure of apoptosis as an important factor in the evolution of colorectal cancer and its poor response to adjuvant therapy. The proto-oncogene bcl-2 suppresses apoptosis. Its expression could provide an important survival advantage permitting the development of colorectal cancer. The expression of bcl-2 and p53 was determined by immunohistochemistry in 47 samples of histologically normal colonic mucosa, 19 adenomas and 53 adenocarcinomas. Expression of bcl-2 in colonic crypts > 5 cm from the tumours was confined to crypt bases but was more extensive and intense in normal crypts < 5 mm from cancers. A higher proportion of adenomas (63.2%) than carcinomas (36.5%) expressed bcl-2 (P < 0.05). A lower proportion of adenomas (31.6%) than carcinomas (62.3%) expressed p53 (P < 0.02). A total of 26.3% of adenomas and 22% of carcinomas expressed both bcl-2 and p53. To determine whether these samples contained cells which expressed both proteins, a dual staining technique for bcl-2 and p53 was used. Only 1/19 adenomas and 2/53 carcinomas contained cells immunopositive for both bcl-2 and p53. Moreover there was evidence of reciprocity of expression of bcl-2 and p53 in these three double staining neoplasms. We suggest that bcl-2 provides a survival advantage in the proliferative compartment of normal crypts and colorectal neoplasms. However, its expression is lost during the evolution from adenoma to carcinoma, whereas p53 expression is increased, an event generally coincident with the expression of stabilised p53, which we presume to represent the mutant form.     

Expression of p53, p21/waf, bcl-2, bax, Rb and Ki67 proteins in colorectal adenocarcinomas

This study investigated the combined immunoexpression of p53, p21, bcl-2, bax, Rb and Ki67 proteins in colorectal adenocarcinomas and correlated expression patterns with tumour stage and grade. Paraffin sections from 98 cases of colorectal adenocarcinomas were stained by immunohistochemistry for p53, p21, bcl-2, bax, Rb and MIB-1 (Ki67) proteins. In addition, 12 cases of colorectal adenomas and normal colorectal mucosa were studied in parallel. P53, p21, bcl-2, bax, Rb and Ki67 proteins were detected in at least 5% of tumour cells in 63/98, 72/98, 52/98, 96/98 and 98/98 adenocarcinomas, respectively. Comparative study of the normal-adenoma-carcinoma tissues revealed abrogation of the normal immunotopography in adenomas and adenocarcinomas, and considerable modifications, increase or reduction, of the expression of p53, p21, bcl-2, bax, Rb and Ki67 proteins in adenocarcinomas when compared with normal mucosa and adenomas. Statistically significant correlations were found between low bax expression and Dukes C stage of carcinomas, Ki67 expression and carcinoma grade, and Ki67 and Rb expression. P53, p21, bcl-2 and Rb immunoexpression did not correlate with tumour stage or grade. Our findings show that low bax immunoexpression is frequently related to colorectal adenocarcinomas with lymph node metastases suggesting that low levels of bax expression play a role in late stage colorectal cancer. The correlation between Ki67 and Rb expression, in view of previous data that the hyperphosphorylated inactive Rb protein is frequently increased in colorectal adenocarcinomas, suggests that Rb protein is somewhat ineffective in inhibiting the cell-cycle progression in these malignancies. Furthermore, our findings provide immunohistochemical evidence that the abrogation of the normal immunotopography and the modifications of the expression of p53, p21, bcl-2, bax, Rb and Ki67 proteins reflect important events in colorectal oncogenesis.     

IGF-ⅡmRNA、bcl-2蛋白在结肠直肠腺癌组织中的表达及临床意义

背景与目的胰岛素样生长因子-Ⅱ(Insulin-likegrowthfactorⅡ,IGF-Ⅱ)能促进细胞分裂、增殖,B细胞淋巴瘤-2(bcl-2)蛋白能明显抑制细胞的凋亡,使细胞寿命延长.近来发现两者在结肠直肠癌中均存在过表达,但两者在结肠直肠癌中的联合检测尚未见报道.本文通过观察结肠直肠腺癌中IGF-ⅡmRNA、bcl-2蛋白的表达情况,结合肿瘤中细胞增殖和凋亡状态的研究,探讨IGF-Ⅱ,bcl-2基因表达的相关性以及与结肠直肠腺癌浸润、转移的关系,并探求两者联合检测的临床意义.方法选取48例结肠直肠腺癌石蜡标本,采用原位分子杂交检测IGF-ⅡmRNA,S-P法检测bcl-2蛋白,增殖细胞核抗原(PCNA),TUNEL法检测细胞凋亡,多媒体图文分析系统定量肿瘤阳性细胞率.以10例正常结肠直肠组织作为对照.结果结肠直肠腺癌中IGF-ⅡmRNA,bcl-2蛋白阳性细胞率[(38.70±7.80)%和(30.97±7.40)%]均显著高于正常结肠直肠组织[(23.12±4.07)%和(12.69±1.31)%](P<0.01),IGF-ⅡmRNA和bcl-2蛋白表达呈负相关(P<0.05),且均与肿瘤Dukes′分期有关和淋巴结转移有关,而与患者的年龄,性别,肿瘤大小,部位,分化程度无关.IGF-ⅡmRNA与PCNA,细胞凋亡显著正相关(P<0.01),bcl-2蛋白与细胞凋亡显著负相关(P<0.01),而与PCNA表达无关(P>0.05).IGF-ⅡmRNA阳性而bcl-2蛋白阴性者预后最差.结论结肠直肠腺癌中IGF-Ⅱ,bcl-2的过表达共同参与了肿瘤的发生,发展,浸润,转移,两者联合检测有一定的临床意义.     

结直肠肿瘤微血管计数及血管内皮细胞生长因子表达

目的 探讨血管生成与结直肠肿瘤的发生,发展关系,评估微血管计数（ＭＶＤ值）及血管内皮细胞生长因子（ＶＥＧＦ）表达与结直肠肿瘤预后的相关性。方法 应用免疫组化法回顾性地研究了３２例结直肠肿瘤石蜡包埋的病理组织。结果 正常粘膜,腺瘤,癌组织的ＭＶＤ值递增。不同病理状态下的结直肠癌ＭＶＤ值有差异,ＶＥＧＦ阴性组ＭＶＤ值低于ＶＥＧＦ阳性组,低ＭＶＤ值主ＶＥＧＦ阴性组生存率高于高ＭＶＤ值组及ＶＥＧＦ阳性组。     

Expression of phosphorylated Ser70 of Bcl-2 correlates with malignancy in human colorectal neoplasms.

PURPOSE: Bcl-2 is a model apoptosis suppressor postulated to promote tumorigenesis. Recently, it has been reported that Bcl-2 undergoes phosphoregulation of its Ser70 to substantially alter its molecular function. Previous studies further suggest that such phospho-Bcl-2 regulation may influence tumor progression in colorectal and other cancers; however, phosphorylation status of the Ser70 of Bcl-2 (pSer70) in vivo in tumors remains obscure. To elucidate this question that may suggest the biological role, we molecularly screened a panel of human colorectal adenomas and adenocarcinomas for endogenous expression of pSer70 Bcl-2. EXPERIMENTAL DESIGN: An antibody specific against pSer70 Bcl-2 was generated for thorough immunohistochemical examination of paraffin-embedded tumor specimens, allowing detection of the endogenously expressed antigen among a range of Bcl-2-positive colorectal neoplasms, including 75 tubular adenomas, 114 adenocarcinomas, and 15 cases of cancer in adenomas. RESULTS: Loss of pSer70 Bcl-2 expression was observed in adenocarcinomas in a differentiation-dependent manner (positivities: well differentiated 63%, moderately differentiated 52%, and poorly differentiated 12%), whereas tubular adenomas maintained their expression (positivity 88%). Interestingly, an inverse correlation was found between expression of pSer70 Bcl-2 and Ki-67 antigen in those cases of cancer in adenoma (P < 0.01). It was further observed that loss of pSer70 Bcl-2 expression was associated with significantly shorter survival (P < 0.05) and correlated with clinical stages and lymph node metastasis (P < 0.05 and P < 0.05, respectively). CONCLUSIONS: Loss of pSer70 Bcl-2 expression is closely linked to biological aggressiveness in colorectal tumors and represents a statistically significant molecular index for prognosis of patients with these tumors.     

食管癌组织中COX-2、p53和PCNA的表达及意义

目的 :研究食管癌组织中环氧合酶 2 (COX 2 )、p53和增殖细胞核抗原 (PCNA)的表达及意义。方法 :采用免疫组化染色 (EnVision及S P)法 ,检测 82例食管鳞状细胞癌、2 0例食管炎和 1 6例正常食管粘膜组织标本中COX 2、P53和PCNA的表达。结果 :82例食管癌组织中COX 2、p53和PCNA的阳性表达率分别为 87.8% (72 82 ) ,82 .9% (68 82 )和 95 .1 % (78 82 ) ,而癌旁及正常组织中均呈阴性表达。COX 2在高分化和中分化食管癌中的表达率显著高于低分化癌 (P <0 .0 1 ) ;无淋巴结转移者表达率高于有淋巴结转移者 (P <0 .0 5)。p53的过表达与浸润深度和淋巴结转移呈正相关 (P <0 .0 1 )。结论 :COX 2、P53和PCNA的过表达可能均参与了食管癌的发生发展过程     

CD44V6在结直肠癌组织中的表达及临床意义

目的：探讨CD44V6表达与结直肠癌发生、发展及转移的关系。方法：采用S－P免疫组织化学方法，检测78例原发性结直肠腺癌、14例结直肠腺瘤癌变、57例结直肠腺瘤、30例结直肠增生性息肉和24例结直肠正常黏膜中CD44V6的表达情况。结果：腺瘤、腺瘤癌变和腺癌组织中CD44V6阳性表达率分别为78．95％、100．00％和56．41％，明显高于增生性息肉和正常黏膜组织的阳性表达率（14．81％）。CD44V6阳性表达与腺癌淋巴结转移、Dukes分期和病理分级无相关性。结论：CD44V6表达与结直肠癌的发生有关，可作为诊断结直肠癌前病变和早期癌的生物学指标。     

结直肠癌组织中E-钙黏素表达及其临床意义

目的　探讨E -钙黏素在结直肠癌组织中的变化及其与结直肠癌临床病理因素的关系。方法　应用免疫组化方法检测 5 2例结直肠癌、10例结直肠腺瘤、8例正常肠黏膜组织中E -钙黏素的表达情况。结果　结直肠癌E -钙黏素弱表达率或阴性表达率 (3 4.6% ,3 6.6% )明显高于结直肠腺瘤、正常肠组织 (P <0 .0 5 ) ;E -钙黏素表达与结直肠癌远处转移明显相关 (P <0 .0 5 ) ,与肿瘤大小、淋巴结侵犯、浆膜浸润无关 (P >0 .0 5 ) ,低分化者E -钙黏素弱表达率或阴性表达率明显高于中分化、高分化者(P <0 .0 5 ) ,随Duke分期进展 ,E -钙黏素阴性表达率或弱表达率逐渐增高 ,DukeD、C与DukeB、A比较有显著性差异 (P <0 .0 5 )。结论　E -钙黏素与结直肠癌生物学行为密切相关。     

bcl-2, p53 and proliferating cell nuclear antigen expression is related to the degree of differentiation in thyroid carcinomas.

Thyroid carcinomas are heterogeneous in terms of histology, clinical presentation, treatment response and prognosis. Since bcl-2 and p53 gene alterations are frequently involved in both lymphoid and epithelial malignancies, we analysed the expression of bcl-2, p53 and proliferating cell nuclear antigen (PCNA) in a group of 134 patients with thyroid neoplasms. The same markers were evaluated in fetal and adult normal thyroids as well as in 40 benign lesions. The study was carried out by immunocytochemistry on archival material using antibodies against bcl-2 and p53 protein on tissue sections of 40 adenomas (As), 20 medullary carcinomas (MCs), 70 well-differentiated carcinomas (WDCs), 20 poorly differentiated carcinomas (PDCs) and 24 undifferentiated carcinomas (UCs). bcl-2 immunoreactivity was detected in 36 out of 40 (90%) As, 20 out of 20 (100%) MCs, 60 out of 70 (85.7%) WDCs, 20 out of 20 (100%) PDCs, and 8 out of 24 (33.3%) of UCs. p53 expression was present in 11.4% of WDCs, 5% of PDCs, 5% of MCs and 62.5% of UCs. By contrast, no p53 immunoreactivity was detected in 40 adenomas and in all the normal thyroid tissues studied. We observed a positive correlation between the expression of p53 and PCNA (r = 0.42; P = 0.035) in a group of UCs, but not in WDCs, PDCs and MCs. Neither p53 nor bcl-2 expression were correlated with clinicopathological parameters, such as age, sex, pTNM and survival. Our results suggest that in tumours of the follicular epithelium p53 and bcl-2 protein abnormalities are associated with more advanced carcinomas and especially with undifferentiated carcinomas, while they are only rarely altered in tumours of the parafollicular C cells.