p16蛋白表达异常与肺癌的关系

目录探讨p16蛋白表达异常与肺癌的关系。方法采用辣根酶标记链霉亲和素免疫组化方法,对35例肺癌组织及相应的癌旁正常肺组织标本和10例肺良性疾病肺组织标本进行研究。结果癌周正常肺组织、肺良性疾病肺组织p16蛋白阳性率均显著高于肺癌组织;临床I,II期p16蛋白阳性率显著高于临床Ⅲ、Ⅳ期;高、中、低分化肺癌细胞p16蛋白表达无显著性差异,男、女肺癌患者p16蛋白表达无显著性差异。结论肺癌的发生可能与p16基因表达产物缺失有关,p16基因的缺失在肺癌进展中起着一定的作用,有可能同时成为预测病程进展的指标之一。     

p16、Rb和cyclin D1蛋白在横纹肌肉瘤中的表达及其意义

目的：探讨细胞周期相关蛋白表达异常与横纹肌肉瘤（RMS）的关系。方法：应用S－P免疫组化方法观察p16,Rb和cyclinD1蛋白在RMS中的表达状态。结果：p16,Rb和cyclinD1蛋白表达阳性率分别为55．3％,61．7％和51．1％,在胚胎性横纹肌肉瘤（ERMS）,p16和Rb蛋白表达阳性率为75．0％（21／28）和67．9％（19／28）,明显高于在腺泡状横纹肌肉瘤（ARMS）中的表达（P＜0．05）,p16蛋白阳性率在I,Ⅱ级横纹肌肉瘤分别为75．0％和73．3％,高于Ⅲ级横纹肌肉瘤（45．0％）;p16蛋白阴性及cyclinD1蛋白过表达组,局部浸润,复发或转移发生率高于p16蛋白阳性及cyclinD1蛋白阴性组;11／47例（23．4％）出现两种以上蛋白表达异常。结论：P16,Rb和cyclinD1蛋白异常可能与部分横纹肌肉瘤发生发展有关,且横纹肌肉瘤的发生可能涉及两种以上基因异常。     

细胞周期调控基因在鼻咽癌发生中的表达

目的　研究 p16、Rb蛋白在各型鼻咽粘膜中的表达及意义。 方法　选择鼻咽粘膜慢性炎、癌前病变及鼻咽癌组织各 30例 ,采用免疫组化LSAB法检测p16、Rb蛋白在上述组织中的阳性表达率。结果　在鼻咽粘膜慢性炎、癌前病变及鼻咽癌组织中 p16蛋白的阳性表达率分别为 10 0 % (0 / 30 )、6 0 % (18/ 30 )及 2 6 .7% (8/ 30 ) ;Rb蛋白的阳性表达率为 76 .7%(2 3/ 30 )、5 6 .7% (17/ 30 )及 33 .3 % (10 / 30 )。经统计学分析 :p16、Rb蛋白在鼻咽粘膜慢性炎症中的阳性表达率高于癌前病变组织 ,差异有显著性 (P <0 .0 1和P <0 .0 5 ) ;p16蛋白在鼻咽癌组织中的表达较癌前病变组织显著下调 (P <0 .0 1) ,而Rb蛋白在两者间的差异无显著性 (P >0 .0 5 )。p16、Rb蛋白的阳性表达率在炎症及癌前病变组织中呈负相关性 (P <0 .0 1) ,而在鼻咽癌组织中二者则无相关性。结论　p16基因的畸变在鼻咽癌的发生中具有直接的促成作用 ;而Rb基因的变异则是鼻咽粘膜癌变的早期事件 ,对鼻咽癌的发生起着间接的促进作用     

p16基因在肺癌中表达的研究

癌症是一种危害人类健康的恶性疾病,目前研究表明,许多细胞周期调节因子与癌症的发生和发展有着密切的关系。细胞周期蛋白依赖性激酶抑制因子ｐ１６,其编码基因为ＭＴＳ１／ｐ１６ＣＤＫ４Ｉ,简称ｐ１６基因,为该研究领域较引人注目的研究热点。自１９９４年美国的Ｋａｍｂ［１］和Ｃａｒ－ｓｏｎ首次发表了有关ｐ１６基因的研究工作以来,人们对其进行了大量的研究。ｐ１６基因编码一个相对分子质量为１６×１０３的蛋白质,此蛋白质是一种细胞周期蛋白依赖性激酶４（ＣＤＫ４）的抑制因子（ＣＤＫ４Ｉ）。我们应用免疫组化Ｓ－Ｐ方法…     

宫颈鳞癌中p16、p21WAF1、Rb、cyclinE蛋白的表达

目的通过观察p16、p21WAF1、Rb、cyclinE 4种细胞周期相关蛋白在宫颈鳞状细胞癌中的表达,探讨它们在宫颈癌的细胞周期调控中的作用.方法采用免疫组化Eli Vision二步法对88例宫颈鳞癌组织,16例宫颈上皮内病变(CIN)组织,15例宫颈炎组织进行p16、p21WAF1、Rb、cyclinE 4种蛋白表达的检测.结果p16、p21WAA1、cyclinE在宫颈癌中的表达高于宫颈炎(P＜0.05);Rb在宫颈癌的表达少于宫颈炎(P＜0.05);Rb与p16在宫颈癌中的表达呈负相关(r=-0.675,P＜0.05).结论宫颈癌细胞周期G1期中,由于Rb蛋白的缺失,使cyclinE表达升高,致使癌细胞增生;同时,p16、p21WAF1蛋白在宫颈癌中的表达增高,并失去抑制作用.     

cyclinD1、p16、Rb在胸腺瘤中表达及预后意义

目的：探讨ｃｙｃｌｉｎ Ｄ１、ｐ１６、Ｒｂ蛋白在胸腺瘤中表达及预后意义。方法；应用免疫组化Ｓ－Ｐ法，对５４例胸腺瘤标本进行检测。结果：ｃｙｃｌｉｎＤ１、ｐ１６，Ｒｂ蛋白在髓质型，混合型胸腺瘤中阳性表达率分别为２３．１％（３／１３）、６９．２％（９／１３），５３．９％（７／１３），器官样，普通皮质型胸腺瘤中阳性表达率分别为５０．０％（８／１６）、７５．０％（１２／１６）、７５．０％（１２／１６），高     

p53/Rb细胞转导通路相关基因和蛋白在衰老大鼠睾丸组织的表达

目的 通过检测p53、Rb、p16、p19、p21在衰老大鼠睾丸组织的表达,探讨p53/Rb细胞转导通路相关基因和蛋白在睾丸组织衰老中的意义. 方法 选用8周龄雄性SD大鼠30只,体重180～220g,随机分为正常对照组和模型组,每组15只.模型组大鼠采用D-半乳糖连续腹腔注射建立亚急性衰老大鼠模型.采用RT-PCR方法 检测p53、Rb基因在大鼠睾丸组织的表达;Western blotting法检测大鼠睾丸磷酸化Rb、p16、p19、p21蛋白的表达.结果 模型组睾丸组织p53、Rb基因表达明显高于正常对照组(P<0.01);模型组睾丸组织与正常组比较:p16、p19、p21蛋白的表达明显升高,而磷酸Rb蛋白表达显著下降(P<0.01). 结论 Rb/p53细胞转导通路相关基因及蛋白在衰老大鼠睾丸组织发生明显改变,Rb/p53细胞转导通路阻滞可能在睾丸组织的衰老过程中起着一定作用.     

p16与p27蛋白在宫颈癌中的表达及意义

宫颈癌是威胁妇女生命健康的主要恶性肿瘤，目前低年龄组宫颈癌的患病率有上升趋势，因此对宫颈癌发病机制的研究倍受关注。宫颈癌中很少见到p53基因改变，检测p16、p27蛋白在宫颈癌及其周围正常宫颈组织的表达，有利于探讨它们与宫颈癌发生、发展的关系。     

p16与细胞周期调节蛋白在食管癌中的表达

细胞周期的调控异常与肿瘤的发生密切相关。其中，ｃｙｃｌｉｎＤ１细胞周期依赖性蛋白激酶４（ＣＤＫ４）ｐ１６，这一以ＣＤＫ４为中心的细胞周期调控途径较为明确，且其各组分的异常与肿瘤的关系十分密切，我们用免疫组化方法对４３例原发食管癌中的ｐ１６、ｃｙｃｌｉｎＤ１、ＣＤＫ４蛋白的存在状态进行了研究，旨在探索其相互的作用及与食管癌发生的关系。一、材料和方法１．标本：４３例食管癌组织取自河南医科大学第二附属医院和河南省肿瘤医院１９９６～１９９７年的手术切除标本。患者术前未接受过放、化疗。每例标本分别取癌…     

肺癌组织p16和Rb基因mRNA表达的双重原位杂交观察

目的：研究Ｐ１６和Ｒｂ基因在ｍＲＮＡ表达及其与肺癌的关系。方法：制备ｐ１６和Ｒｂ基因ｃＤＮＡ探针,采用双重原位杂交的方法,地８９例肺癌和正常肺组织进行了Ｐ１６ 一Ｒｂ基因ｍＲＮＡ表达的定位研究。结果：小细胞肺癌ｐ１６ｍＲＮＡ阳性表达率高达８２．４％,而非小细胞肺癌阳性率为４５．８％,两者差异有显著性。非小细胞肺癌ＲｂｍＲＮＡ阳性表达率为８１．９％,而小细胞肺癌一率仅５．９％,两者差异有高度显著性,     

肺癌中P16蛋白阳性表达的价值

目的：探索Ｐ１６蛋白表达与肺癌（ＬＣ）的关系。方法：应用免疫组织化学技术（Ｓ－Ｐ法）检测１４３例ＬＣ组织中Ｐ１６蛋白的表达。结果：ＬＣ中Ｐ１６蛋白表达阳性率为５９．３７％，其中腺癌（ＡＣ）为６３．１９％、磷状细胞癌（ＳＣＣ）为６０．２８％、腺鳞癌（ＡＳＣ）为５５．１１％、小细胞癌（ＳＣ）为２６．００％、肺泡细胞癌（ＢＡＣ）为７４．５２％。Ｐ１６蛋白阳性表达率在ＳＣ与ＡＣ、ＳＣＣ及ＢＡＣ比较，其差异     

Immunohistochemical overexpression of p16 protein associated with intact retinoblastoma protein expression in cervical cancer and cervical intraepithelial neoplasia

Both p16 and retinoblastoma (Rb) proteins are important tumor supprsssors that regulate the cell cycle. The status of both proteins In lnvasive cervical cancer and cervical intraepithelias neopiasis (CIN) has not yet been examined. The aim of this study was to investigate the expression of p16 and Rb proteins by immunohlstochemistry using 98 formalln-fixed and paraffin-embedded samples of various cervical neoplastic lesions. Strong immunoreactiyity for the p16 protein was observed in both the nuclei and cytoplasm of all CIN and lnvasive cancer cases except several low-grade CIN lesions. Expression of Rb protein was also demonatrated In the scattered nuclel of neoplastic and normal cells in all cases Investigated. The results suggest that the deletion or mutational inactivity of both p16 and Rb proteins may be a rare event In cervical carcinogenesls. Moreover, overexpression of the p16 protein may be a useful dlagnostic marker for cervical neoplastic lesions on routine laboratory screening.     

Clinical significance of p16 protein expression loss and aberrant p53 protein expression in pancreatic cancer

Pancreatic cancer is a disease with poor prognosis mainly due to low resection rates and late diagnosis. To increase resectability and improve survival rates, a better understanding of pancreatic cancer pathogenesis and more effective screening techniques are required. New methods, such as genetic and molecular alterations, may suggest novel approaches for pancreatic cancer diagnosis and treatment. We immunohistochemically investigated 44 formalin-fixed, paraffin-embedded specimens of pancreatic ductal adenocarcinoma using monoclonal anti-p16 antibodies and monoclonal anti-p53 antibodies. The expressions of p16 and p53 proteins were compared using the Chi-square test with SPSS. Disease-free survival was analyzed using the Kaplan-Meier method, verified by the Log- Rank test. Loss of p16 expression was noted in 20 (45.5%) cases and aberrant p53 protein expression was detected in 14 (31.8%) cases. Loss of p16 expression was associated with a higher incidence of lymph node metastasis (p=0.040) and a more advanced stage (p=0.015), although there was no significant correlation between p16 expression and survival. Aberrant p53 protein expression correlated with histologic grade (p= 0.038). Disease-free survival rate was significantly lower in the aberrant p53 protein positive group compared to the negative group (p=0.029). From our results, we suggest that p53 is not a prognostic factor; however, p16 and p53 genes do play important roles in the progression of pancreatic ductal adenocarcinoma.     

Alterations of expression of Rb,p16INK4A and cyclin D1 in non-small cell lung carcinoma and their clinical significance

Inactivation of the Rb pathway in non-small cell lung carcinoma (NSCLC) occurs mostly through inactivation of the cyclin-dependent kinase inhibitor p16^INK4A and/or up-regulation of cyclin D1. In order to assess the frequency and the prognostic value of these abnormalities in NSCLC, immunohistochemical analysis of Rb, p16^INK4, and cyclin D1 has been performed on 168 cases of NSCLC including 77 squamous cell carcinomas, 43 adenocarcinomas, and 48 basaloid carcinomas. The reduced survival rate of basaloid carcinoma (stage I–II) compared with other histological types of NSCLC was confirmed (p = 0·008). Loss of protein expression of Rb and p16^INK4A was observed in 12 per cent and 58 per cent of NSCLC cases respectively and cyclin D1 overexpression in 43 per cent. There was an inverse correlation between Rb and p16 expression ( p < 0·0001) and a direct correlation between Rb and cyclin D1 expression ( p = 0·0007). In univariate analysis, Rb-negative adenocarcinomas at stages I–II had a significantly shorter survival than Rb-positive cases ( p = 0·04) and stages I–II p16-positive cases had a shorter survival than p16-negative cases ( p = 0·02), which was more significant in basaloid carcinoma ( p = 0·003). p16 status retained its influence on survival in multivariate analysis at stage I–II for all cases ( p = 0·01) and for basaloid carcinoma ( p = 0·005). Cyclin D1 overexpression did not influence survival. Combined Rb/p16/cyclin D1 phenotypes in univariate analysis showed a shorter survival for Rb-negative/p16-positive/cyclin D1-negative tumours ( p = 0·002). These results, linked to previous data, indicate that the Rb pathway of G1 arrest is initially disrupted in the vast majority of NSCLCs (83 per cent), but could not confirm an unfavourable role for each individual event (p16^INK4A loss or cyclin D1 up-regulation) in prognosis. Copyright © 1999 John Wiley & Sons, Ltd.     

Aberrant LRP16 protein expression in primary neuroendocrine lung tumors

Background: The Leukemia related protein 16 gene (LRP16) localized on chromosome 11q12.1, is an important estrogen-responsive gene and a crucial regulator for NF-kB activation. LRP16 is frequently expressed in human cancers; however, the LRP16 gene remains unexplored in lung neuroendocrine tumors. The aim of this study was to investigate the role of LRP16 expression in primary lung neuroendocrine tumors. Methods: lung neuroendocrine tumors were analyzed for LRP16 gene expression by two-step non-biotin immunohistochemical method. Results: Fifty of ninety (55.6%) cases of neuroendocrine lung tumors tested were positive for LRP16 protein by immunohistochemistry. The expression of LRP16 was mainly located in cytoplasm and nucleus of tumor cells. LRP16 protein was corresponding to tumor type and clinical stage, as well as survival time. Conclusions: The results indicate that abnormal LRP16 expression is noted in neuroendocrine lung tumors and the expression can give insight into the pathogenesis of the disease. The LRP16 protein may serve as a potential marker in predicting prognosis of neuroendocrine lung tumors.     

乳腺癌EGFR、p16蛋白表达与预后的关系

目的 :研究EGFR和 p16蛋白在人乳腺癌中表达及其与预后关系。 方法 :用免疫组化LSAB法 ,检测 5 4例乳腺癌中EGFR和p16蛋白的表达情况 ,并用HPLAS - 10 0 0高清晰度彩色病理图文分析系统进行定量测定。 结果 :EGFR的表达强度在乳腺癌组织学分级、淋巴结转移和预后方面差异有显著性 (P <0 0 5 ) ;p16蛋白与乳腺癌预后之间有差异 (P <0 0 5 )。结论 :检测EGFR和 p16蛋白对判断乳腺癌预后有重要意义     

肺癌CDKN2/p16基因纯合缺失的研究

目的　研究 Ｃ Ｄ Ｋ Ｎ２／ｐ１６ 基因的缺失与肺癌发生、发展的关系。方法　采用多重聚合酶链反应技术,对８９ 例肺癌进行了 Ｃ Ｄ Ｋ Ｎ２／ｐ１６ 基因第１ 、２ 外显子纯合缺失的分析研究。结果　标本取材方法的改良提高了聚合酶链反应技术对基因缺失的检出率,８９ 例肺癌中检出第１ 外显子缺失率１９ ．１ ％ （１７／８９） ,第２ 外显子缺失率２２ ．５ ％ （２０／８９） ,有１４ 例第１ 、２ 外显子共同缺失,第１ 或（ 和） 第２ 外显子总缺失率为２５８ ％ （２３／８９） 。 Ｃ Ｄ Ｋ Ｎ２／ｐ１６ 基因的缺失集中发生于非小细胞肺癌, 并与转移和分期有关。结论 Ｃ Ｄ Ｋ Ｎ２／ｐ１６ 基因的缺失是非小细胞肺癌的遗传易感因素,并在其恶性进展中起一定作用。     

软组织平滑肌肉瘤中肿瘤抑制基因p15,p16的表达

目的：探讨p15,p16蛋白在软组织平滑肌肉瘤（LMS）及平滑肌瘤（LM）的表达情况及其意义,方法：采用免疫组织化学方法检测38例LMS及20例LM标本的p15,p16蛋白表达情况,结果：在LMS,p15,p16的阴性率分别为18．42％及42．1％,二者差异有显著性。p15在LM的阴性率为60％,高于LMS。38例LMSp15和p16总异常率为52．6％,其中Ⅰ级LMS异常率显著高于Ⅱ、Ⅲ级。随访15例LMS,复发死亡组p15和p16异常率达75％,高于无复发组。结论：在LMSp16表达缺失比p15缺失更为常见,p15的缺失在LM在比在LMS常见,LMS的发生发展及预后p15及p16共同失活有关。