前列腺癌中 P504S、34βE12、p63 的检测及意义

目的:探讨P504S、p63、34βE12在前列腺腺癌中的表达和诊断意义.方法:应用免疫组化法观察30例前列腺癌(PCa)、49例良性前列腺增生(BPH)、6例不典型腺瘤样增生(AAH)和29例前列腺上皮内瘤变(PIN)组织中P504S、p63、34βE12的表达.结果:28例PCa阳性表达P504S,1例灶性阳性,5例PIN灶性阳性表达P504S;P504S在PCa组阳性明显高于BPH、AAH、和PIN组(P＜0.01),灶性阳性表达在两组之间无明显差异(P＞0.05).1例PCa灶性阳性表达p63和34βE12,49例BPH、4例AAH和26例PIN为p63和34βE12阳性,2例AAH和3例PIN为灶性阳性,PCa组p63和34βE12阳性表达明显低于其他病变组(P＜0.01),灶性阳性表达在两组之间无明显差异(P＞0.05).结论:P504S是前列腺癌敏感而特异性的标记物,合理利用P504S、p63、34βE12的检测,可提高前列腺癌的诊断准确率和检出率.     

前列腺癌中P504S、34βE12、p63的检测及意义

目的：探讨P504S、p63、34βE12在前列腺腺癌中的表达和诊断意义。方法：应用免疫组化法观察30例前列腺癌（PCa）、49例良性前列腺增生（BPH）、6例不典型腺瘤样增生（AAH）和29例前列腺上皮内瘤变（PIN）组织中P504S、p63、34βE12的表达。结果：28例PCa阳性表达P504S,1例灶性阳性,5例PIN灶性阳性表达P504S;P504S在PCa组阳性明显高于BPH、AAH、和PIN组（P〈0.01）,灶性阳性表达在两组之间无明显差异（P〉0.05）。1例PCa灶性阳性表达p63和34βE12,49例BPH、4例AAH和26例PIN为p63和34βE12阳性,2例AAH和3例PIN为灶性阳性,PCa组p63和34βE12阳性表达明显低于其他病变组（P〈0.01）,灶性阳性表达在两组之间无明显差异（P〉0.05）。结论：P504S是前列腺癌敏感而特异性的标记物,合理利用P504S、p63、34βE12的检测,可提高前列腺癌的诊断准确率和检出率。     

p504S、p63抗体混合离心法在前列腺癌诊断中的应用

 目的　应用在前列腺组织中新型肿瘤标志物p504S蛋白和基底细胞标志物p63的表达，以一次性标记来同步显示双重抗原，以辅助提高前列腺癌诊断的准确率。方法　从837例前列腺标本中，选取前列腺癌标本72例，前列腺上皮内瘤（PIN）标本6例，良性增生标本30例，把抗体混合离心法应用于免疫组织化学标记中，观察p504S、p63在前列腺良性增生、PIN和前列腺癌中的表达。结果　在确诊的72例前列腺癌患者中，p504S阳性61例， p63除1例呈间断阳性外其余71例均阴性。6例PIN中，p504S阳性5例，p63均为阳性。而30例良性增生则表现为p504S 29例阴性，p63 27例阳性。结论　p504S和p63抗体混合离心法双标记的应用，将极大地提高前列腺癌的诊断准确率。     

Atg5与P504S在82例前列腺癌中的表达研究

摘 要：［目的］ 探讨Atg5与P504S在前列腺癌中的表达情况。［方法］ 收集前列腺癌（PCa）、良性前列腺增生症（BPH）及前列腺上皮内瘤（PIN）的组织标本共127例,其中PCa组织标本82例,BPH组织标本25例,PIN组织标本20例。采用免疫组化法检测Atg5与P504S在不同病变组织中的表达情况。［结果］ Atg5与P504S在PCa组织中的阳性率均显著高于BPH及PIN组织,差异具有统计学意义（P<0.05）。P504S的阳性表达程度与病理分级、临床分期以及肿瘤转移有关,而与患者年龄无关。Atg5的表达与年龄、病理分级、临床分期以及肿瘤转移均无显著相关性（P>0.05）。Atg5与P504S在PCa组织中的表达呈正相关（P<0.05）。［结论］ Atg5与P504S的异常表达与前列腺癌密切相关,且P504S与前列腺癌进展呈正相关,在前列腺癌诊断中具有较高的临床价值。     

p63和p504S联合检测在前列腺肿瘤鉴别诊断中的应用

目的探讨p63和p504S联合免疫组化染色在前列腺良、恶性病变鉴别诊断中的价值。方法采用免疫组化方法，观察p63、p504S在不同前列腺疾病中的表达情况。结果大多数良性前列腺增生及低度PIN的腺泡和导管周围可见连续的p63（＋），少数呈间断表达，p504S染色皆呈（-）；高度PINp63染色呈不连续表达或（-），而增生的腺上皮，部分细胞p504S呈弱（＋）或（＋）；非典型腺瘤性增生p63呈（＋），p504S呈阴性反应；前列腺癌20例中19例p63染色呈（-），1例显示局灶性（＋），但p504S均呈（＋）。结论p63、p504S联合检测可极大地提高前列腺癌诊断的正确率。     

前列腺癌组织中p27和Survivin的表达与前列腺特异性抗原的相关性

目的:通过分析蛋白p27和Survivin在前列腺癌(PCa)组织中的阳性表达与前列腺特异性抗原(PSA)的相关性,探讨前列腺癌的治疗方法.方法:应用免疫组织化学方法检测75例前列腺癌和60例前列腺增生组织中p27、Survivin蛋白的表达和相应患者血浆中的PSA值.结果:前列腺癌组织中p27、Survivin蛋白的阳性表达率分别为37.3%(28/75)、68.0%(51/75),p27和Survivin蛋白在前列腺增生组织中的阳性表达率分别为63.3%(38/60)、0(0/60),在前列腺增生和前列腺癌组织中Survivin和p27蛋白的阳性表达率差异均具有统计学意义(P<0.05).p27和Survivin蛋白表达与前列腺癌病理分级、临床分期、转移情况和PSA值具有统计学意义(P<0.05).结论:临床中联合检测p27及Survivin表达与前列腺特异性抗原的关系和相互作用机制,为前列腺癌的防治和治疗提供新的思路.     

CK34βE12、p63和P504S联合检测在前列腺癌诊断中的应用

 目的 探讨CK34βE12、p63和P504S联合免疫组化标记在前列腺良、恶性病变鉴别诊断中的应用价值。方法 应用免疫组织化学方法，观察74例前列腺病变标本[包括前列腺癌（PC）27例、高级别前列腺上皮内瘤（HGPIN）6例、低级别前列腺上皮内瘤（LGPIN）10例、前列腺非典型腺瘤性增生（AAH）3例、良性前列腺增生（BPH）28例]中CK34βE12、p63和P504S的表达情况。结果 p63和CK34βE12在AAH、LGPIN和BPH中均为阳性染色，而在PC中均为阴性，在6例HGPIN中5例为阳性，PC组表达率明显低于其他病变组差异有统计学意义（P＜0.01）；P504S 在PC、AAH、HGPIN、LGPIN和BPH中阳性率分别为92.6 %（25／27）、0、66.7 %、10 %和0，PC组明显高于AAH、LGPIN和BPH组（P＜0.01），与HGPIN组之间差异无统计学意义（P = 0.132）；P504S阳性协同p63或CK34βE12阴性两种标记在PC、AAH、HGPIN、LGPIN和BPH中表达率分别为92.6 %、0、16.7 %、0和0，两种标记表达在前列腺癌与其他病变之间差异有统计学意义（P＜0.01）。结论 利用P504S与p63或CK34βE12联合检测有助于提高前列腺癌诊断的准确率。     

免疫组化P504S、p63、34βE12在前列腺病变组织中的表达

目的探讨P504S、p63、34βE12在前列腺病变组织中的表达,以评估其在鉴别诊断中的意义。方法应用免疫组化PV9000二步法检测43例前列腺腺癌、27例前列腺重度上皮瘤变、40例前列腺结节性增生组织中P504S、p63、34βE12的表达情况。结果P504S在前列腺癌性腺体与重度上皮瘤变、前列腺结节性增生腺体组织中的阳性表达率之间均有非常显著性差异(P<0.01);但在Gleason评分分值显示,不同的前列腺腺癌组织中的表达无显著性差异(P>0.05);p63、34βE12在所有前列腺癌腺体组织中均呈阴性,在重度上皮瘤变组织中呈弱阳性、阳性或强阳性,在前列腺结节性增生组织中均呈强阳性。结论P504S是前列腺腺癌敏感而特异性的标志物,其与p63、34βE12联合标记在前列腺病变的鉴别诊断中具有重要意义,为临床早期发现、早期治疗前列腺腺癌提供了有力的理论依据。     

免疫组化在前列腺癌诊断中的作用

目的观察p504S、p63、CK34βE12在前列腺癌诊断和鉴别诊断中的价值.方法用免疫组化S-P法检测p504S、p63、CK34βE12在前列腺癌、PIN和前列腺良性增生中的表达.结果 72例前列腺癌中61例p504S阳性,但p63和CK34βE12大部分阴性.6例PIN中5例p504S阳性,但p63和CK34βE12均阳性.而良性增生表现为p504S阴性,p63和CK34βE12阳性.结论 p504S和p63、CK34βE12联合检测可极大地提高前列腺癌诊断的准确率.     

P504S、p63、34βE12在前列腺不同病变诊断中的意义

目的 探讨P504S、p63、34βE12在良性前列腺增生、不典型腺瘤样增生、前列腺上皮内瘤变和前列腺腺癌诊断中的意义.方法 收集102例前列腺不同病变的常规石蜡标本,光镜下按WHO标准分类,应用免疫组织化学二步法,观察PS04s、p63、34βE12的表达.结果 良性前列腺增生、不典型腺瘤样增生的腺泡和导管周围34βE12和p63均为(+),而P504S均(-).低级别PIN及高级别PIN的腺泡和导管周围34βE12和p63均为(+),而增生的腺上皮P504S分别为7.7%(2/26)、33.3%(1/3)呈局灶性阳性.前列腺腺癌18例中,34βE12和p63均为(-),P504S有2例呈局灶性阳性(11.1%),15例P504S呈阳性(83.3%).结论 P504S是前列腺腺癌敏感而特异性的标记物,联合检测PS04S、p63、34βE12可提高前列腺腺癌的诊断准确率,对前列腺穿刺标本进行不同病变的鉴别诊断更有帮助.     

p29ING4 and p28ING5 bind to p53 and p300, and enhance p53 activity

We identified and characterized two new ING family genes, p29ING4 and p28ING5,coding for two proteins of 249 and 240 amino acids, respectively. Both p29ING4 and p28ING5 proteins have a plant homeodomain finger motif also found in other ING proteins, and which is common in proteins involved in chromatin remodeling. p29ING4 or p28ING5 overexpression resulted in a diminished colony-forming efficiency, a decreased cell population in S phase, and the induction of apoptosis in a p53-dependent manner. Both p29ING4 and p28ING5 activate the p21/waf1 promoter, and induce p21/WAF1 expression. p29ING4 and p28ING5 enhance p53 acetylation at Lys-382 residues, and physically interact with p300, a member of histone acetyl transferase complexes, and p53 in vivo. These results indicate that p29ING4 and p28ING5 may be significant modulators of p53 function.     

INK4系列抑癌基因纯合子缺失、甲基化与白血病预后的实验研究

 目的　研究INK4系列抑癌基因纯合子缺失、甲基化与白血病预后的关系。方法　采用聚合酶链反应（PCR）研究p16基因家族在白血病中纯合子缺失,应用甲基化敏感限制内切酶HpaⅡ结合PCR技术研究白血病患者p16、p15、p18、p19 基因甲基化状况,用单因素、多因素Logistic回归分析其基因失活与急性白血病（AL）预后的关系。结果　基因表达组治疗有效27例（84.38 %）,基因失活组治疗有效11例（28.95 %）,基因表达组治疗有效率明显高于基因失活组（P＜0.001）。单因素、多因素Logistic回归分析结果显示p16、p15 基因失活化疗有效率明显低于基因表达组。结论　p16、p15基因失活可作为AL病程进展、复发、预后的指标之一。     

p53基因家族的新成员 p73和 p63

p53作为广泛存在的肿瘤抑制基因,最近发现了其家族成员：p73和p63。它们在结构和功能上具有相似性,均能触发细胞周期停滞,诱导凋亡,但它们在肿瘤抑制和组织发育中起着截然不同的作用,深入了解它们彼此之间的相似性和差异将对理解肿瘤发生的机制产生重要的影响。本文总结了最近几年来此领域内的最新进展。另外,p73和p63在C端的SAM结构说明它们可能参与组织的发育过程。     

p53 protein variants: structural and functional similarities with p63 and p73 isoforms

Since its discovery in 1979, many studies have reported that the p53 tumour suppressor protein could be expressed in the form of products smaller than those predicted by the full-length amino-acid sequence. These products differ from full-length p53 in their N- or C-terminal regions, but generally conserve the central, DNA-binding domain. They appear to be expressed at rather low levels and to be restricted to particular cell types and/or physiological circumstances, suggesting that they play very narrow and specific roles. Several mechanisms have been proposed to explain their timely occurrence, including alternative splicing, internal initiation of translation or proteolytic cleavage. A precise assessment of the various 'p53 isoforms' reveals striking similarities with several isoforms of the p53 homologous proteins p63 or p73, suggesting that regulated production of specific, N- or C-terminal variants may be a 'trademark' of all family members. In this review, we summarize the published evidence on the structure, mode of production, expression and function of the p53 isoforms, and discuss their properties in the light of recent data on the structure and function of p63/p73 isoforms.     

Tumorigenesis in p27/p53- and p18/p53-double null mice: functional collaboration between the pRb and p53 pathways

Mice lacking both p18(Ink4c) and p27(Kip1) develop a tumor spectrum similar to pRb(+/-) mice, and loss of p53 function accelerates tumorigenesis in pRb(+/-) mice. We hypothesized that codeletion of either p18 or p27 in conjunction with p53 deletion will also accelerate tumorigenesis. Mice lacking both p18 and p53 develop several tumors not reported in either single null genotype, including hepatocellular carcinoma, testicular choriocarcinoma, hemangiosarcoma, leiomyosarcoma, fibrosarcoma, and osteosarcoma. Mice lacking both p27 and p53 exhibit a decreased lifespan and develop unique tumors, including papillary carcinoma of the colon, hemangiosarcoma, and leiomyosarcoma. In both p18/p53 and p27/p53 double null genotypes, the incidence and spectra of tissues that develop lymphoma are also increased, as compared to the single null genotypes. The development of p27/p53 double null colon tumors correlates with secondary changes in cell-cycle protein expression and CDK (cyclin-dependent kinase) activity, perhaps contributing to the progression of colorectal cancer. We concluded that p18 and p27 can, not only functionally collaborate with one another, but also can independently collaborate with p53 to modulate the cell cycle and suppress tumorigenesis in a tissue-specific manner.     

Role of p53 family members p73 and p63 in human hematological malignancies

Abstract p53, mutated in over half of human cancers and about 13% of all hematological malignancies, maintains genomic integrity and triggers cellular senescence and apoptosis of damaged cells. In contrast to p53, the homologs p73 and p63 play critical roles in development of the central nervous system and skin/limbs, respectively. Moreover, dependent on the context they can exert tumor suppressor activities that cooperate with p53. Unlike p53, p73 and p63 are rarely mutated in cancers. Instead, up-regulation of the anti-apoptotic dominant-negative ΔNp73 and ΔNp63 isoforms is the most frequent abnormality in solid cancers. In hematological malignancies the most frequent p73 defect is promoter methylation and loss of expression, associated with unfavorable clinical outcomes. This suggests an essential tumor suppressor role of p73 in blood cells, also supported by genetic mouse models. Many therapeutic approaches aiming to restore p73 activity are currently being investigated. In contrast, the most frequent p63 abnormality is protein overexpression, associated with higher disease grade and poorer prognosis. Surprisingly, although available data are still scarce, the emerging picture is up-regulation of transactivation-competent TAp63 isoforms, suggesting a tumor-promoting role in this context.     

p73和p63蛋白在胰腺癌组织中过表达的意义

目的:探讨p53家族新成员p73和p63蛋白在胰腺癌组织中过表达的意义。方法:应用免疫组化LSAB法检测75例人胰腺癌组织中p73和p63蛋白的过表达。结果:p73和p63蛋白在人胰腺癌中的过表达率分别为46·7%(35/75)和42·7%(32/75),p73蛋白在胰腺囊腺癌中的过表达率88·9%(8/9)明显高于导管腺癌41·8%(23/55),P=0·009,且p73蛋白过表达与胰腺癌淋巴结转移、肿瘤大小、神经侵犯和p53表达呈显著负相关性,P<0·05;在腺鳞癌或腺癌伴鳞状上皮化生中p63蛋白的过表达率(100%,13/13)明显高于导管腺癌(40·0%,22/55),P=0·007,但p63蛋白过表达与胰腺癌临床病理学指标及p53和增殖细胞核抗原(pro-liferatingcellnuclearantigen,PCNA)表达间无明显相关性。结论:p73蛋白低表达可能在胰腺癌发生中起重要作用;p63蛋白过表达与腺鳞癌或腺癌鳞化有关。     

A Comparative Study of Glioma Cell Lines for p16, p15, p53 and p21 Gene Alterations

A total of 10 glioma cell lines were examined for alterations of the p16, p15, p53 and p21 genes, which are tumor suppressor genes or candidates with direct or indirect CDK-inhibitory functions. Genetic alterations (deletions or mutations) were frequently seen in the p16, p15 and p53 genes in these cell lines, but not in the p21 gene. When the states of the p16, p15 and p53 genes were compared among cell lines, all the cell lines showed abnormalities in at least 1 gene, often in 2 or 3 genes coincidentally, suggesting that dysfunction of these genes is closely related to glioma cell growth. Although alteration of all 3 genes was most frequent, there were cell lines having either p16/p15 or p53 or p16 and p53 gene alterations, suggesting that the time order of these genetic alterations was variable depending on the cell line. Among cell lines examined, one with homozygous p53 gene deletion seemed of particular practical value, since such a cell line might be useful in various studies, including investigation of the functions of various mutant p53 genes in the absence of heteromeric protein formation. On examination of the primary tumor tissues, the same alterations of the p16/p15 and p53 genes as detected in the cell lines were demonstrated in all 6 cases examined: p16/p15 gene deletion in 1, p16 gene mutation in 1 and p53 gene mutations in 5 cases. This suggested that the p16/p15 and the p53 gene alterations and their combinations in at least some glioma cell lines reflected those in the primary glioma tissues.