p53蛋白和MDM 2蛋白在食管鳞状细胞癌中的表达及意义

为了探讨肿瘤抑制基因ｐ５３和癌基因ＭＤＭ２在食管鳞状细胞癌中的表达及其意义，采用免疫组织化学链菌素亲生物素蛋白过氧化物酶连接法（ＳＰ法），检测了６８例食管鳞状细胞癌中ｐ５３蛋白和ＭＤＭ２蛋白的表达，结果显示ｐ５３蛋白和ＭＤＭ２蛋白阳性率分别为６０．３％（４１／６８）和４２．６％（２９／６８），ｐ５３蛋白阳性率与食管鳞状细胞癌分级呈显著正相关（Ｐ＜０．０１），ＭＤＭ２蛋白阳性率与食管鳞状细胞癌分级呈显著负相关（Ｐ＜０．０１），并与食管鳞状细胞癌临床病理分期呈显著负相关（Ｐ＜０．０５）。在６８例食管鳞状细胞癌中，ｐ５３蛋白阳性表达者４１例，其中ｐ５３蛋白和ＭＤＭ２蛋白表达均阳性者１２例，ＭＤＭ２蛋白表达阴性者２９例；在６８例食管癌中，ＭＤＭ２蛋白阳性表达者２９例，其中ＭＤＭ２与ｐ５３蛋白均阳性者１２例，ｐ５３蛋白表达阴性者１７例，两者呈显著负相关（Ｐ＜０．０１），ｐ５３蛋白和ＭＤＭ２蛋白表达均阴性者１０例。可以认为ｐ５３蛋白和ＭＤＭ２蛋白表达可作为食管鳞状细胞癌病理分级参考指标之一，ＭＤＭ２蛋白表达还可作为食管鳞状细胞癌临床病理分期的参考指标之一，并间接证明ＭＤＭ２蛋白对ｐ５３蛋白表达具有负性调节作用。     

p53和c—myc异常表达与膀胱癌多药耐药性

为探讨ｐ５３和ｃ－ｍｙｃ基因异常表达与膀胱癌多药耐药性（ＭＤＲ）的关系，应用ＡＢＣ免疫组织化学方法检测６７例膀胱癌癌细胞中ｐ５３和ｃ－ｍｙｃ的表达产物及多药耐药基因（ｍｄｒ－１）产物Ｐ－ｇｐ。结果显示ｐ５３突变蛋白蓄积的膀胱癌中Ｐ－ｇｐ阳性表达率９２．３％；ｐ５３阴性者Ｐ－ｇｐ阳性率为３６．６％。Ｐ－ｇｐ表达与ｐ５３突变蛋白蓄积呈显著正相关（ｒ＝０．６４，Ｐ＜０．０５）；而ｃ－ｍｙｃ和ｍｄｒ－１的表达无明显相关。提示：ｐ５３异常表达可增加ｍｄｒ－１基因的表达，使膀胱癌细胞获得ＭＤＲ表型     

膀胱癌中CD15与p53的表达及相关性研究

目的研究ＣＤ(１５)和抑癌基因蛋白产物在膀胱癌组织中的表达及与病理分级、临床分期、复发和转移的关系,并探讨ＣＤ(１５)与抑癌基因蛋白表达的相关性。方法应用微波－ＬＳＡＢ免疫组织化学法,检测５２例膀胱癌组织中ＣＤ(１５)和ｐ５３的表达水平。结果在膀胱癌中ＣＤ(１５)和ｐ５３阳性表达率分别为６９．２％和４８．１％。其表达均与肿瘤分级、分期、复发和转移相关（Ｐ＜０．０５）。ＣＤ(１５)和Ｐ５３表达里正相关。结论ＣＤ(１５)和Ｐ５３均是膀胱癌高度恶性和预后不良的重要生物学指标。膀胱癌ＣＤ(１５)表达与Ｐ５３蛋白表达可能具有相互协同作用。     

横纹肌肉瘤P53,MDM2基因及p53,p21,p185蛋白表达检测比较

目的：探讨ｐ５３、ｐ２１、ｐ１８５蛋白表达及ｐ５３、ＭＤＭ２基因与横纹肌肉瘤（ＲＭＳ）分化和预后的关系，并对几种检测方法进行了比较。方法：应用免疫组化方法检测ＲＭＳｐ５３、ｐ２１、ｐ１８５蛋白表达，银染ＰＣＲＳＳＣＰ检测ＲＭＳｐ５３的突变，原位杂交检测ＲＭＳｐ５３和ＭＤＭ２基因。结果：ｐ５３、ｐ２１、ｐ１８５蛋白在ＲＭＳ的阳性率分别为６７２％（４１／６１）、６８（３４／５０）、６０％（３０／５０）；检测３０例ＲＭＳ，ｐ５３基因７例发生点突变原位杂交检测ＲＭＳ的ｐ５３、ＭＤＭ２基因突变的检出率分别为６６７％和７７４％；上述结果均与年龄、性别、肿瘤组织类型无关，而与肿瘤分化转移和预后有关。结论：ｐ５３、ｐ２１、ＭＤＭ２蛋白表达及癌基因检测均有助于判断肿瘤恶性程度和肿瘤预后，上述３种方法比较，免疫组化与原位杂交检测的阳性结果基本相符，提示免疫组化方法同样能反映肿瘤恶性程度和预后，是一种简便可行的检测方法。     

胃癌p16,p53和CD44V6的表达特点及其意义

目的 探讨ｐ１６、ｐ５３和ＣＤ４４Ｖ６在胃癌发生、发展及淋巴结转移的作用机理和意义。方法 用免疫组化ＡＢＣ法检测ｐ１６、ｐ５３和ＣＤ４４Ｖ６在９３例胃癌组织中的表达。结果 ９３例胃癌中ｐ１６、ｐ５３和ＣＤ４４Ｖ６的阳性表达率分别为３９．８％、５０．５％、４１．９％。ｐ１６蛋白在淋巴结转移阳性表达率３０．８％,显著低于淋巴结转移阴性的阳性表达率６０．７％（Ｐ〈０．０１）。ｐ５３在进展期胃癌、淋巴结转     

大肠癌内分泌样癌细胞分化与p53蛋白聚集变化关系的研究

采用免疫组织化学ＡＢＣ法检测６６例经１０％福尔马林固定，石蜡包埋的大肠癌手术切除癌组织中的嗜铬蛋白Ａ（ＣｈｒｏｍｏｇｒａｎｉｎＡ，ＣＧＡ）表达及ｐ５３蛋白聚集，并定量计数ｐ５３免疫阳性细胞，进一步分析ＣＧＡ与ｐ５３蛋白聚集变化的关系，结果显示：大肠癌ｐ５３ＣＧＡ阳性率分别为６１％（４０／６６）和３８％（２５／６６）；ＣＧＡ阳性及阴性病例ＣＧＡｐ５３阳性率分别为８０％（２０／２５）和４９％（２０／４１），ＣＧＡ阳性肿瘤ｐ５３阳性率明显高于ＣＧＡ阴性肿瘤（χ２＝６．３４，Ｐ＜０．０２５）；ｐ５３、ＣＧＡ均阳性的大肠癌２０例ｐ５３阳性细胞数为８５７±７０６／ｍｍ２，ｐ５３阳性、ＣＧＡ阴性表达者２０例ｐ５３阳性细胞数５７１±４７８／ｍｍ２，前者高于后者（ｔ＝２．３３，Ｐ＜０．０５）。结论：ｐ５３蛋白聚集与内分泌样癌细胞的分化呈现较明显的一致性，这种ｐ５３肿瘤抑制基因的变化可能是影响大肠癌内分泌样癌细胞分化的重要分子学改变     

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。     

大肠肿瘤cyclin D1、p21WAF1/CIP1、p53和增殖细胞核抗原的免疫组化研究

目的：探讨细胞周期调控因子表达在大肠肿瘤发生发展中的作用及其预后的影响。方法：彩免疫组化染色对１１３例大肠癌、１４例大肠腺瘤、１１例腺瘤癌变组织中ｃｙｃｌｉｎＤ１、ｐ＾２１＾ＷＡＦ１／ＣＩＰＩ、ｐ＾５３和ＰＣＮＡ进行了检测。结果：大肠癌组织ｃｙｃｌｉｎＤ１和ｐ＾５３阳性表达率分别为５４．８７％和５６．６４％,均显著高于正常大肠组织（Ｐ〈０．０５）。高分化腺癌ｐ＾２１蛋白阳性表达率６９．７０％,低分     

人乳腺癌细胞株WAF1/CIP1/p21基因的表达及其与细胞生物学特性的关系

目的研究人乳腺癌细胞株ＷＡＦ１／ＣＩＰ１基因的ＤＮＡ状况、ｍＲＮＡ和蛋白的表达水平及其意义。方法应用细胞培养、分子生物学Ｓｏｕｔｈｅｒｎｂｌｏｔ和Ｎｏｒｔｈｅｒｎｂｌｏｔ杂交以及免疫组化染色等技术，检测人乳腺癌表达野生型ｐ５３（ｗｔｐ５３）的ＭＣＦ７细胞和表达突变型ｐ５３（ｍｔｐ５３）的ＭＤＡＭＢ２３１细胞中ＷＡＦ１／ＣＩＰ１基因ＤＮＡ状况、ｍＲＮＡ和蛋白质的表达水平，研究其与ｍｄｍ２、ｐ５３蛋白的表达和细胞生物学特性的关系。结果比较ＭＣＦ７细胞与ＭＤＡＭＢ２３１细胞：（１）两者ＷＡＦ１／ＣＩＰ１基因ＤＮＡ状况无明显差异，前者ｍＲＮＡ和蛋白质的表达水平明显高于后者（Ｐ＜０．０５）；（２）两者ｐ５３蛋白的性质和分布不同，前者ｍｄｍ２蛋白的表达水平明显高于后者（Ｐ＜０．０５）；（３）前者生物学特性好于后者。结论人乳腺癌细胞株ＷＡＦ１／ＣＩＰ１基因ｍＲＮＡ和蛋白质的表达水平与ｐ５３基因表型和细胞生物学特性有关。     

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。     

MDM2、P53蛋白在星形细胞瘤中的表达

目的　探讨 MDM2、p5 3蛋白在星形细胞瘤发病中的作用及其与肿瘤病理分级、预后的关系。方法　对确诊并有随访的 36例星形细胞瘤标本用免疫组化技术 SABC法进行 MDM2、p5 3蛋白定位观察。结果　发现 MDM2及 p5 3蛋白表达阳性率分别为 44 .4% (16 / 36例 )和 38.9% (14/ 36例 ) ,其阳性率与年龄、性别无关 ,但与肿瘤病理分级呈显著正相关 (分别为 P<0 .0 5 ,P<0 .0 1)。在 36例星形细胞瘤中MDM2和 p5 3共同阳性表达 9例 (2 5 % ) ,这 9例与单独MDM2蛋白或 p5 3蛋白阳性表达病例及 MDM2和 p5 3蛋白表达均阴性病例的一年和三年存活率有显著差别 (分别为P<0 .0 5 ,P<0 .0 1)。结论　 MDM2、p5 3蛋白阳性检出率有助于判断星形细胞瘤的恶性程度及预测肿瘤的预后     

人脑胶质瘤p53基因突变及MDM2、p16、p53蛋白表达与临床病理特征相关性研究

目的:探讨p53突变在人脑胶质瘤发生发展中的作用及p53蛋白蓄积与突变的符合程度,并研究MDM2、p16、p53蛋白表达与胶质瘤临床病理特征的关系以及三者的相关性。方法:利用聚合酶链反应-单链构象多态性分析法(PCR-SSCP)及LSAB免疫组化法对已明确诊断的48例人脑胶质瘤进行p53基因突变以及MDM2、p16、p53蛋白表达的检测。结果:48例胶质瘤中20例p53蛋白呈阳性表达(41.7%)。PCR-SSCP检测发现17例(35.4%)呈现p53基因的单链构象多态性改变,均位于5～8外显子,突变例数依次为7(41.2%)、1(5.9%)、4(23.5%)、5(29.4%)。两种方法检测的符合率为89.6%(43/48)。MDM2、p53蛋白阳性率分别为22.9%、41.7%,p16表达缺失率为60.4%。在高级别(Ⅲ、Ⅳ级)的肿瘤中p53表达率及p16表达缺失率分别为63.2%、84.2%,均明显高于低级别(Ⅱ级)的肿瘤(分别为27.6%、44.8%)(P<0.05)。在不同分级的胶质瘤中,MDM2表达率及阳性程度没有显著差异。在p53阳性表达的病例中常伴有p16的表达缺失(57.6%),而且大多出现在Ⅲ、Ⅳ级肿瘤中(9/12)。p53突变、三种分子的表达均与患者的年龄、性别、肿瘤的大小及发病部位无相关性。结论:胶质瘤中p53基因的突变与胶质瘤的发生及恶性进展相关,p53蛋白蓄积与突变率较一致。MDM2基因异常参与胶质瘤的发生,是其形成的早期事件;p16、p53在胶质瘤中的异常表达与肿瘤的分化程度相关。     

肝细胞肝癌p21WAF1与p53的表达及其意义

目的探讨HCC中p21     

p53, p21, Rb, and MDM2 proteins in tongue carcinoma from patients < 35 versus > 75 years

Relatively rare squamous cell carcinomas of the tongue in young patients may be associated with different etiologic factors and pathogenetic mechanisms than carcinomas from the same site in older patients. Alterations in cell cycle proteins likely contribute to the biologic behavior of these neoplasms. The purpose of this investigation was to evaluate cell cycle proteins (p53, p21, Rb, MDM2) in lateral tongue cancers from patients at the two ends of the age spectrum. All available archived lateral tongue carcinomas from patients < 35 years (n = 36, 23 males and 13 females) were sectioned, immunohistochemically stained, and evaluated. Protein expression was scored as percent positive nuclei. An equal number of sequentially accessioned lateral tongue specimens from patients > 75 years (23 males and 13 females) were stained and compared. Positive p53 staining was seen in 18/36 of the < 35-year group versus 24/36 of the > 75-year group (p = 0.149). Increased p21 staining (both percent of positive cells and intensity) was evident in 25/32 of the < 35-year group versus 24/32 of the > 75-year group (p = 1.0). Increased p21 expression was seen in both p53-positive and -negative cases in both age groups. Rb protein was increased in 16/29 of the < 35-year group versus 17/26 of the > 75-year group (p = 0.58). Fourteen cases (4/35 vs 10/36, p = 0.135) showed positive MDM2 staining; MDM2-positive cases were also p53 positive in 4/4 younger and 8/10 older patients. We conclude that p53, p21, Rb, and MDM2 are over-expressed in lateral tongue cancers, and that immunohistochemical profiles are heterogeneous. A p53-independent pathway of p21 induction is supported by the results; p53 suppression may be associated with MDM2 protein expression in a subset of cancers. Significant differences in the expression of p53, p21, Rb, and MDM2 proteins are not evident in lateral tongue carcinomas from patients < 35 years as compared to patients > 75 years.     

Tumorigenic pathways in low-stage bladder cancer based on p53, MDM2 and p21 phenotypes

Our aim was to determine whether the pattern of expression of the interrelated proteins p53, MDM2 and p21 could shed light on the etiopathogenic mechanisms of superficial bladder tumors. Protein expression was detected by immunohistochemistry (IHC) using monoclonal antibodies (MAbs) Pab 1801 for p53, IF2 for MDM2 and EA10 for p21 on 269 newly diagnosed bladder tumors (214 pTa and 55 pT1; 93 grade I, 145 grade 2 and 31 grade 3). While no p21 immunoreactivity was found in normal urothelium, 85% of tumors were strongly p21-positive. MDM2 was overexpressed in 44% of tumors, almost all being also positive for p21. p53 was overexpressed in 20% of cases: 66% of p53-positive tumors were also MDM2 positive, compared with only 38% of p53-negative tumors. p53 mutations were studied by direct DNA sequencing in a subset of 24 high-grade tumors. Both MDM2 and p21 were less frequently expressed in p53 mutated tumors compared with tumors with a wild-type gene. Distinct phenotypes were correlated with the frequency of poorly differentiated (grade 3) tumors. The most common phenotypes were p21+/MDM2-/p53- and p21+/MDM2+/p53- observed in 38% and 29% of tumors, respectively. Grade 3 tumors were found in 4% and 8% of these 2 groups, in contrast with 30% frequency in p21+/p53+ tumors (p = 0.002) regardless of their MDM2 phenotype. Four of the 5 (80%) tumors that were p53-positive but negative for p21 were grade 3. Our data suggest that several tumorigenic pathways for superficial bladder tumors can be reflected by the expression pattern of these 3 proteins.     

紫外线照射对卵巢癌细胞NFkB、P53和MDM2的影响

目的：研究NFkB家族蛋白、P53和MDM2在卵巢癌细胞系的表达及紫外线照射后所引起的变化。方法：培养11株卵巢癌细胞系，收获细胞，对其进行胞质、胞核蛋白质提取，Western印迹法观察NFkB家族蛋白及其抑制物的表达，并观察p53和MDM2的表达；采用20J／m^2剂量紫外线照射细胞，继续培养并提取蛋白质进行检测。结果：11个卵巢癌细胞系p50、p65和IKB-α细胞质表达阳性率分别为63．6％、45．5％、81．9％，胞核表达阳性率分别为63．6％、54．5％、18．2％。紫外线照射后胞核p50、D65和IKB-α阳性率分别为81．9％、72．7％、36．4％。p53在卵巢癌细胞表达阳性率为45．5％，MDM2表达阳性率为27.3％，紫外线照射后p53和MDM2表达阳性率分别为63．6％、72．7％。结论：NFkB、p53和MDM2与卵巢癌细胞的发生、发展有关；紫外线照射可引起胞核NFkB及细胞MDM2阳性率明显提高。NFkB和MDM2可望成为判断卵巢癌预后新的标志物。     

Clinical significance of p53, MDM2 and bcl-2 expression in transitional cell carcinoma of the bladder

We investigated the prognostic and predictive relevance of p53, MDM2, and bcl-2 protein expression in patients with transitional cell carcinoma (TCC) of the bladder. The expression of p53, MDM2 and bcl-2 protein was studied by immunohistochemical methods in paraffin-embedded specimens from 119 patients whose clinicopathologic data confirmed TCC of the bladder. Multivariate analyses of prognostic factors were performed, and correlations with classical clinicopathologic parameters were examined. Sixty-one, 12, and 17% of cases were considered positive for expression of p53, MDM2 and bcl-2, respectively. p53 expression correlated with stage (p=0.0209), but not MDM2 and bcl-2 with any clinicopathologic parameters. In Cox's regression analysis, staging demonstrated a statistically worse prognosis (hazard ratio 1.636; p=0.0059) while bcl-2 (hazard ratio 0.179; p=0.0474) expression showed favorable prognosis in stage T2-4 invasive TCC of the bladder. Co-expression with p53/MDM2 (hazard ratio 0.367; p=0.0401) and p53/bcl-2 (hazard ratio 3.487; p=0.0111) overexpression were associated with favorable and unfavorable prognosis in stage T2-4 invasive TCC of the bladder, respectively. Our results indicate that staging is the most useful parameter to predict clinical outcome in patients with TCC of the bladder. Determinations of bcl-2 and co-expression p53/MDM2 and p53/bcl-2 may be useful for predicting tumor behavior and prognosis in stage T2-4 invasive type TCC of the bladder.     

The prognostic value of MDM2 overexpression in superficial urothelial bladder carcinoma

The prognostic significance of p53 accumulation and MDM2 overexpression in superficial and papillary urothelial cell carcinoma (UCC) of the bladder has not yet been established. Therefore, MDM2 and p53 protein were investigated focusing on tumour grade and muscularis mucosae invasion in order to identify their prognostic significance. Thirty-five archival UCC were studied by immunohistochemistry using monoclonal antibodies DO7 against p53, and IB10 against MDM2. MDM2 overexpression was observed in 51.4% of the cases. The recurrence rate for patients with MDM2 overexpression was 7.09 fold higher than for those without MDM2 overexpression. p53 accumulation was not related to prognosis. There was no significant difference between low and high grade tumours in regard to MDM2 overexpression and p53 accumulation. pTa cases presented the higher frequency of MDM2 positive cases (66.7%) and a lower frequency of p53 accumulation (33.3%). MDM2 overexpression does not seem to be related to muscular mucosae invasion. Thus, MDM2 status may well be a prognostic marker in superficial urothelial bladder carcinomas.     

骨肉瘤组织中p53蛋白表达与PCNA的相关性研究

目的 研究骨肉瘤组织中ｐ５３蛋白表达与ＰＣＮＡ的相关性。方法 应用免疫组化方法测定３３例骨肉瘤中ｐ５３基因、ＰＣＮＡ的表达,均行手术治疗,１９例获得平均１年７个月的随访,１１例发生肺转移（６例死亡）３例术后复发。结果 ｐ５３阳性表达率为５７．６％,预后良好组ｐ５３阳性表达率明显低于预后不良组;ＰＣＮＡ阳性表达率为６６．７％。结论 ｐ５３蛋白阳性表达的骨肉瘤有较强的增殖能力。     

Dysfunction of p53 pathway in human colorectal cancer: analysis of p53 gene mutation and the expression of the p53-associated factors p14ARF, p33ING1, p21WAF1 and MDM2

Mutations of p53 tumor suppressor gene increase with tumor progression in colorectal cancers. In this study, we examined the expressions of p33ING1, p14ARF, MDM2 and p21WAF1 mRNA in 25 advanced colorectal cancers by quantitative RT-PCR method, and compared the expression levels of p33ING1, p14ARF, p21WAF1 and MDM2 in relation to p53 status in the tumors. Fifteen of 25 colorectal cancers (60%) showed abnormal accumulation of p53 protein in the nucleus, and the remaining 10 colorectal cancers (40%) were negative for p53 immunostaining. We found a G --> T transition (nonsense mutation) at the first nucleotide of codon 298 (exon 8) in one p53-negative case, and a frame shift mutation on exon 7 in another p53-negative case. In remaining eight p53-negative cases, there was no mutation in the entire open reading frame of p53 cDNA. Interestingly, in eight cases with p53 wild-type gene, 6 cases (75%) showed a marked down-regulation of p14ARF mRNA, and three cases (37.5%) over-expressed MDM2 mRNA. Only one case with wild-type p53 gene showed normal level expression of p53 regulatory-factors (p33ING1, p14ARF, and MDM2). Thus, p53 tumor suppressor pathway was disrupted in 24 of 25 colorectal cancers (96%).