p16、细胞周期蛋白D1和pRb在头颈部鳞癌的表达及其意义

目的：探讨ｐ１６、细胞周期蛋白Ｄ１（ｃｙｃｌｉｎＤ１）和ｐＲｂ头颈部鳞癌（ｈｅａｄ ａｎｄ ｎｅｃｋ ｓｑｕａｍｏｕｓ ｃｅｌｌ ｃａｒｃｉｎｏｍａ,ＨＮＳＣＣ）的表达及他们的相互关系和其意义。方法：应用免疫组织化学方法检测３２例原发ＨＮＳＣＣ患者癌组织中ｐ１６、ｃｙｃｌｉｎＤ１和ｐＲｂ的蛋白表达。结果：ｐ１６、ｃｙｃｌｉｎＤ１、ｐＲｂ的总异常率为９０．６％（２９／３２）,其中ｐ１６和ｐＲｂ蛋白表     

p16和cyclinD_1蛋白在膀胱移行细胞癌中的表达及意义

 目的探讨ｐ１６、ｃｙｃｌｉｎＤ１蛋白表达与膀胱移行细胞癌（ＴＣＣ）临床分期、病理分级及预后的关系。方法采用免疫组化Ｓ－Ｐ法检测 ５９例膀胱ＴＣＣ中ｐ１６、ｃｙｃｌｉｎＤ１蛋白的表达。结果膀胱ＴＣＣ 组织中 ｐ１６蛋白阳性表达率为 ４２．４％，随临床分期、病理分级增高而下降，ｃｙｃｌｉｎＤ１蛋白阳性表达率为 ６１％，随临床分期增高而上升；ｐ１６、ｃｙｃｌｉｎＤ１蛋白表达间呈负相关；ｐ１６阳性组和 ｃｙｃｌｉｎＤ１阴性组复发率明显低于 ｐ１６阴性组和ｃｙｃｌｉｎＤ１阳性组；ｐ１６阳性组和 ｃｐｃｌｉｎＤ１阴性组 ３年存活率明显高于 ｐ１６阴性组和 ｃｙｃｌｉｎＤ１阳性组。结论ｐ１６、ｃｙｃｌｉｎＤ１蛋白检测可作为膀胱ＴＣＣ辅助诊断及预后判断的参考指标。     

非霍奇金淋巴瘤CyclinD1和p34^cdc2蛋白的检测

为了研究非霍奇金淋巴瘤（ＮＨＬｓ）中细胞周期调节因子ＣｙｃｌｉｎＤ１和ｐ３４＾ｃｄｃ２蛋白表达与肿瘤分化程度和免疫分型的关系,对４０例ＮＨＬｓ进行ＣｙｃｌｉｎＤ１和ｐ３４＾ｃｄｃ２蛋白免疫组化（ＳＰ法）染色。在４０例ＮＨＬｓ中,有１９例（４７．５％）ＣｙｃｌｉｎＤ１阳性表达２３例（５７．５％（ｐ３４＾ｃｄｃ２阳性表达。１０例淋巴结良性病变中６例生发中心细胞ＣｙｃｌｉｎＤ１和ｐ３４＾ｃｄｃ２弱 是必     

p16、CyclinD1、Cdk4、Rb基因在胰腺癌中的表达及其意义

目的：探讨ｐ１６,ＣｙｃｌｉｎＤ１,Ｃｄｋ４,Ｒｂ在胰腺癌中的作用及其相互关系。方法：免疫组织化学检测ｐ１６,ＣｙｃｌｉｎＤ１,Ｃｄｋ４,Ｒｂ蛋白在胰腺癌中的表达,原位杂交检测ｐ１６和ＣｙｃｌｉｎＤ１在胰腺癌中的存在状况。结果：ｐ１６在胰腺癌中低表达,ＣｙｃｌｉｎＤ１呈正相关关系。结论：胰腺癌发生机制涉及ｐ１６,ＣｙｃｌｉｎＤ１,Ｃｄｋ４和Ｒｂ调节环路中多个基因的异常,ｐ１６低表达和ＣｙｃｌｉｎＤ     

胃粘膜病变中多种肿瘤相关基因产物的表达

目的　探讨胃粘膜病变中ｐ１６、ｐ２１、ｐ５３ 蛋白、ｃｙｃｌｉｎＤ１和ＰＣＮＡ表达异常的意义。方法　免疫组织化学（Ｓ－ Ｐ）方法和显微摄像计算机图象分析技术。结果　２２７ 例胃粘膜病变中ｐ１６ 阳性１５２ 例（６６．９％ ）;ｐ２１阳性１３５ 例（５９．５％ ）;ｐ５３阳性２５例（１１．０％ ）;ｃｙｃｌｉｎＤ１ 阳性９７ 例（４２．７％ ）。结论　提示ｐ１６、ｐ２１ 蛋白的低表达和ｐ５３ 蛋白、ｃｙｃｌｉｎＤ１的过表达在胃粘膜细胞增殖癌变过程中起重要作用。     

细胞周期蛋白D1和p21^WAF1／CIP1在喉癌癌变过程中表达？…

目的：研究喉癌变过程中细胞周期蛋白（ｃｙｃｌｉｎ）Ｄ１和ｐ２１＾ＷＡＦＩ／ＣＩＰ１表达及其临床病理学意义。方法：用免疫组化检测２０例正常黏膜、４０例不典型增生病变和６０例喉癌组织中ｃｙｃｌｉｎＤ１和ｐ２１＾ＷＡＦＩ／ＣＩＰ１的表达。结果：①ｃｙｃｌｉｎＤ和ｐ２１＾ＷＡＦＩ／ＣＩＰ１阳性表达定位于细胞核。②在喉癌癌变过程中,喉正常黏膜、不典型增生病变和喉癌中ｃｙｃｌｉｎＤ１阳性表达率分别为：５．０％     

Rb,p16蛋白在大肠癌中的表达及其意义

目的研究Ｒｂ、ｐ１６基因表达的蛋白产物在大肠癌组织中的变化及其意义。方法应用免疫组化ＳＰ法,在４０例原发性大肠癌中检测Ｒｂ、ｐ１６蛋白的表达。结果Ｒｂ蛋白表达阳性率为７２．５％（２９／４０）;ｐ１６蛋白表达阳性率为３７．５％（１５／４０）。２３例ｐ１６蛋白呈阴性或弱阳性表达的大肠癌组织中,Ｒｂ蛋白均显示阳性或强阳性,９例Ｒｂ蛋白呈阴性或弱阳性表达的大肠癌中,ｐ１６蛋白呈阳性或强阳性表达。１５例淋巴结转移的大肠癌中仅２例ｐ１６阳性,而２５例无转移者有１３例ｐ１６阳性。结论大肠癌发生过程中,存在Ｒｂ、ｐ１６蛋白表达的异常,Ｒｂ失活与ｐ１６表达之间存在负相关关系。ｐ１６蛋白表达缺失与大肠癌淋巴结转移有关。     

p16与Rb蛋白在骨肉瘤中的表达及相关性研究

为探讨骨肉瘤中ｐ１６和Ｒｂ蛋白的表达及其相关性，采用免疫组化ＡＢＣ法，对３２例骨肉瘤手术标本使用抗ｐ１６和Ｒｂ蛋白抗体进行检测。结果显示，ｐ１６和Ｒｂ蛋白阳性表达分别为３７．５％（１２／３２）和５６．３％（１８／３２）。在１２例Ｒｂ蛋白阳性或强阳性表达的骨肉瘤中，ｐ１６蛋白表达阴性或弱阳性表达８例（６６．７％）；相反，在１０例Ｒｂ蛋白阴性或弱阳性表达的骨肉瘤中，ｐ１６蛋白阳性或强阳性表达６例（６０．０％）。结果表明：ｐ１６和Ｒｂ蛋白参与骨肉瘤细胞的增殖过程并与骨肉瘤的进展和预后有关；ｐ１６和Ｒｂ蛋白之间阳性表达的相互抑制，可能是判断骨肉瘤恶性程度的标志之一。     

喉癌癌变过程中CyclinE和p53表达的临床病理学意义

目的研究喉癌癌变过程中ＣｙｃｌｉｎＥ和ｐ５３表达的临床病理学意义。方法用免疫组化检测２０例喉正常粘膜、４０例不典型增生病变和６０例喉癌组织中ＣｙｃｌｉｎＥ和ｐ５３的表达。结果ＣｙｃｌｉｎＥ和ｐ５３阳性表达均定位于细胞核。在喉癌癌变过程中,喉正常粘膜、不典型增生病变和喉癌中ＣｙｃｌｉｎＥ阳性表达率分别为５．０％（１／２０）、２０．０％（８／４０）和４５．０％（２７／６０）（Ｐ＜０．００１）。ｐ５３阳性表达率分别为０、３０．０％（１２／４０）和６１．７％（３７／６０）（Ｐ＜０．００１）。淋巴结转移组ＣｙｃｌｉｎＥ阳性表达率明显高于非淋巴结转移组;ＣｙｃｌｉｎＥ和ｐ５３阳性表达显著性相关（Ｐ＜０．０５）。结论ＣｙｃｌｉｎＥ和ｐ５３异常表达可能是喉癌发生中早期分子事件,对喉癌发展起重要作用。     

非霍奇金淋巴瘤中Cyclin D1和p34~(cdc2)蛋白的检测

为了研究非霍奇金淋巴瘤（ＮＨＬｓ）中细胞周期调节因子ＣｙｃｌｉｎＤ１ 和ｐ３４ｃｄｃ２ 蛋白表达与肿瘤分化程度和免疫分型的关系,对４０ 例ＮＨＬｓ 进行ＣｙｃｌｉｎＤ１ 和ｐ３４ｃｄｃ２ 蛋白免疫组化（ＳＰ法）染色。在４０ 例ＮＨＬｓ 中,有１９ 例（４７．５ ％）ＣｙｃｌｉｎＤ１ 阳性表达,２３ 例（５７．５ ％）ｐ３４ｃｄｃ２ 阳性表达。１０ 例淋巴结良性病变中６ 例生发中心细胞ＣｙｃｌｉｎＤ１ 和ｐ３４ｃｄｃ２ 弱阳性表达。低分化ＮＨＬｓ 的ＣｙｃｌｉｎＤ１ 和ｐ３４ｃｄｃ２ 阳性率明显高于高分化ＮＨＬｓ（Ｐ＜ ０．０５）,而同免疫分型无关（ Ｐ＞０ ．０５） 。２ 个细胞周期调节因子的表达具有高度一致性（Ｐ＜０ ．０５）。提示２ 个细胞周期调节因子参与ＮＨＬｓ 的发生发展过程,其阳性表达率及表达强度同ＮＨＬｓ 恶性程度有密切关系,而同免疫分型无明显联系。ＣｙｃｌｉｎＤ１ 和ｐ３４ｃｄｃ２ 蛋白在部分ＮＨＬｓ 中共同起作用,使Ｇ１ →Ｓ期和Ｇ２ →Ｍ 期２ 个细胞检查点控制减弱。     

Overexpression of retinoblastoma protein predicts decreased survival and correlates with loss of p16INK4 protein in gallbladder carcinomas.

This study was designed to determine whether the level of retinoblastoma protein (pRb) expression predicts tumor progression and prognosis in gallbladder carcinomas (GBCs) and the relationship between pRb and pl6INK4 protein expression. The expression of these two proteins was evaluated immunohistochemically in 37 tumors from 36 patients with GBC. pRb loss and overexpression were observed in 5 (13.5%) and 18 (48.6%) of the 37 tumors, respectively. Both pRb loss and overexpression were significantly correlated with advanced TNM stage, lymph node metastasis, and tumor perineural invasion. Moreover, pRb overexpression was significantly associated with decreased overall survival (P = 0.001; log-rank test). Further analysis indicated that the influence of pRb overexpression on survival was independent of TNM stage and lymph node metastasis. Loss of p16INK4 protein was observed in 28 of the 37 GBCs (75.7%), but was not significantly associated with any clinicopathological factors or survival. pRb overexpression was significantly associated with the loss of p161NK4 protein (P < 0.0001). These results suggest that pRb overexpression significantly predicts decreased survival in GBCs.     

p53蛋白及cyclinD1蛋白在胃癌中的表达及临床意义

目的通过联合检查p53蛋白及cyclinD1蛋白在胃癌组织及正常胃组织中的表达,探讨它们与胃癌分化程度的关系。方法应用流式细胞术(FCM)对13例正常胃组织及27例胃癌组织细胞进行p53蛋白及cyclinD1蛋白的检测。结果p53蛋白在正常组的表达均为阴性85.2%(23/27)的胃癌组织p53表达阳性,p53蛋白表达量(F1值)和p53蛋白阳性表达率与胃癌组织分化程度有明显相关性(P<0.01)。cyclinD1蛋白在正常组的表达均为阳性77.8%(21/27)的胃癌组织cyclinD1呈阳性表达,cyclinD1表达量(F1值)和cyclinD1阳性表达率与胃癌组织分化程度有明显相关性(P<0.01)。p53蛋白表达与cyclinD1蛋白表达呈正相关(r=0.678)。结论p53蛋白及cyclinD1蛋白过表达与胃癌组织的分化程度有明显相关性,联合检测p53及cyclinD1蛋白可做为判断胃癌恶性程度的有效指标。p53及cyclinD1蛋白的高表达与胃癌的发生、发展有密切关系。     

Alteration of pRb/p16/cdk4 regulation in human osteosarcoma.

Cell-cycle regulation depends on a fine balance between cyclin-cyclin-dependent kinase complexes and a family of kinase inhibitors that bind cyclin-cdk complexes and block their activity. To investigate the role of mechanisms regulating cell-cycle progression in human osteosarcomas (OS), pRb/p16/cdk4 expression was analyzed in 39 high-grade OS; 19 of these developed metastasis during follow-up. Positive reaction for functional pRB was shown by 18/39 (46%) OS, while 21/39 (54%) were negative. A higher probability of metastasis was seen in patients with negative pRb expression (p < 0.05). Furthermore, while functional pRb and D1 expression are inversely associated to metastasis occurrence, the presence of D1/cdk4 complex in our study was related to poor prognosis. We found that 10/18 pRb-positive and 14/21 pRb-negative tumors were p16-positive. No significant correlation was found between pRb and p16 expression. On the other hand, high cdk4 levels in p16-positive tumors as compared with p16-negative tumors resulted in a positive association between p16 and cdk4 expression (Chi squared = 5.98; p = 0.01). No extensive p16INK4A genomic alterations were found in tumors lacking p16-protein expression. To determine which mechanisms are involved in the down-regulation of p16 protein, the methylation status of the p16INK4 gene was evaluated on the 15 p16-negative tumors: 8 samples showed 5' CpG-island methylation; 4/8 had a complete methylation status, while in the remaining 4 the gene was only partially methylated. These data confirm the role of the pRb/p16/cdk4 pathway in OS development.     

细胞周期相关蛋白在大肠癌中的表达及其意义

目的 探讨细胞周期相关蛋白在大肠癌中的表达及其与大肠癌临床病理特征的关系.方法 应用免疫组化S-P法对70例大肠癌组织及距癌灶3 cm以外的癌旁组织、10 cm以外的正常组织中CyclinDl、CDK4、p16和Pb进行检测.结果 CyclinD1和CDK4在大肠癌中过度表达,分别为36/70(51.4%)和28/70(40.0%),并与肿瘤的分化程度呈反比,有淋巴结转移的大肠癌,其CyclinD1和CDK4的阳性率分别为70.0%和60.0%,无淋巴结转移的大肠癌阳性率分别为44.0%和32.0%,两者相比差异有显著性(P＜0.05),p16在大肠癌中为低表达33/70(47.1%),癌旁组织和正常组织中p16的表达分别为57.1%和71.4%,Rb在大肠癌、癌旁及正常组织中的表达分别为65.7%、78.6%和85.7%.CyclinD1与CDK4呈正相关关系(P＜0.05).CyclinD1与p16、p16与Rb是负相关关系(P＜0.05、P＜0.05).结论 CyclinD1、CDK4的过度表达与肿瘤的分化程度、淋巴结转移密切相关;p16的表达可能受Rb蛋白的负调控;CyclinD1的过度表达和p16的低表达在大肠癌发生中起协同作用;     

p16和Rb基因在人肝细胞癌中的表达

目的：分析p16基因和视网膜母细胞瘤基因（Rb）在人肝癌细胞中表达的改变。方法：用免疫组织化学方法40例肝细胞癌和癌旁组织进行检测。结果：肝组织中的p16蛋白和Rb蛋白的异常表达分别为94．44％（34／36）和45．71％（16／35）。p16蛋白阴性或弱阳性而Rb呈强阳性者13例（13／34,38．23％）,两者的表达呈负相关关系。p16和Rb蛋白均异常者15例（15／34,44．11％）,表明Rb蛋白表达的调节除p16外,还有其他途径。二者的异常表达与肝癌的恶性程度无相关关系。结论：细胞调节因子p16和Rb基因的异常表达,均参与肝细胞癌的发生。以p16蛋白表达的改变为主。     

Clinical significance of P16INK4A and retinoblastoma proteins in non-small-cell lung carcinoma

This study was performed to determine the frequency of expression loss of p16 and pRb; their relations with each other, tumour histology, tumour stage, nodal status, and survival in formalin fixed, paraffin embedded tumour tissues of patients with non-small-cell lung carcinoma (NSCLC). P16 and/or pRb expression loss is observed in 72 (75.8%) out of 95 patients, and 70 (73.7%) of them showed inverse correlation (P<0.05). Thirty-six (37.9%) of the p16 positive cases usually showed weak or moderate immunohistochemical staining. Loss of p16 expression was found to be significantly greater in squamous cell carcinoma than in adenocarcinoma cases, whilst no relation was observed with other clinical parameters. Immunohistochemical reactivity for pRb was generally moderate or strong. PRb expression loss was observed in 15.8% of the cases, and no relation was found between pRb loss and age, sex, tumour histology, tumour stage, or nodal status. PRb negative squamous cell carcinoma cases had significantly shorter survival independent of nodal status. These results suggest that disruption of p16/pRb pathway is frequently involved in NSCLC, and pRb expression loss in cases with squamous cell carcinoma may predict clinical outcome.     

Expression of cell cycle proteins in head and neck cancer correlates with tumor site rather than tobacco use

Head and neck squamous cell carcinomas of non-smoking patients may result from specific defects in cell cycle control. Expression of p53, pRb, p16(INK4a) and Cyclin D1 was examined by immunohistochemistry of biopsies obtained from 24 non-smoking and 25 smoking patients, both groups representing similar clinical features (tumor site, stage of disease, gender).Expression of p16(INK4a) was restricted to carcinomas of the tonsils (8/24), P=0.0069. In 6/8 p16(INK4a)-positive cases, expression of pRb was absent or reduced. p16 was the only marker showing a significant correlation with a negative smoking history (P=0.0208). Overexpression of Cyclin D1 was frequent in carcinomas of the tongue (6/14) but rare in tonsillar carcinomas (2/24), P=0.0303. Expression of p53 was independent of the smoking history and the tumor site.Our results implicate that there are factors other than tobacco consumption which may influence the development of head and neck cancers at distinct tumor sites.