凋亡酶激活因子与p53及Ki-67在结直肠癌和结直肠腺瘤组织中的表达

目的探讨凋亡酶激活因子1(Apaf-1)、p53和Ki-67在结直肠腺瘤、结直肠癌组织中的表达情况。方法采用SP染色法,检测结直肠癌、腺瘤组织中Apaf-1、p53和Ki-67的表达情况。结果结直肠癌淋巴结转移组中,Apaf-1、p53、Ki-67阳性表达率分别为22.7%、31.8%和90.9%,无淋巴结转移组分别为43.6%、89.7%和61.5%,差异均有统计学意义(均P<0.05)。结直肠癌A、B期的Apaf-1、p53、Ki-67阳性表达率分别为43.6%、89.7%和61.5%,C、D期的Apaf-1、p53、Ki-67阳性表达率分别为27.7%、31.8%和90.9%。结直肠癌组织中Apaf-1阳性率(39.0%)低于腺瘤(88.0%),p53阳性率(77.0%)和Ki-67阳性率(68.0%)均高于腺瘤(分别为49.0%、26.0%),差异均有统计学意义(P<0.05)。Apaf-1阳性表达与p53、Ki-67阳性表达均呈负相关(r1=-0.358,r2=-0.361,P<0.01)。结论 Apaf-1、p53与Ki-67表达在结直肠癌、腺瘤的发生、发展与转移过程中有一定影响,对诊断结直肠癌有重要意义。     

结直肠纤维绒毛锯齿状腺瘤临床病理学及免疫组织化学的观察

目的:探讨纤维绒毛锯齿状腺瘤(FSA)的临床病理学特征以及免疫组织化学特征的意义。方法:收集病理诊断为结直肠各类息肉和腺瘤切片5347例,从中筛选出FSA共18例,同时收集临床相关资料并观察病理学特征。对FSA11例、非纤维绒毛锯齿状腺瘤(NFSA)20例〔其中传统锯齿状腺瘤(TSA)15例、广基锯齿状腺瘤/息肉(SSA/P)5例〕、增生性息肉(HP)20例及绒毛管状腺瘤(VTA)20例分别进行免疫组化Ki-67、p53、-βCatenin、CK7、CK20及CDX-2染色。结果:FSA多发于左半结肠,组织学显示肿物表面可见许多细长丝状或绒毛状的突起,隐窝被覆异型增生的上皮细胞,伴有典型锯齿状改变,该类突起形似绒毛管状腺瘤,但其长度比绒毛管状腺瘤长。多数病例突起末端间质水肿明显(12/18),严重者可膨大呈"球茎"状改变(7/18)。FSA异型增生程度较NFSA和VTA要高,差异有统计学意义,P<0.05。在FSA中p53和Ki-67的表达与其他各组比较差异有统计学意义,P<0.05。结论:FSA是一种较少见的特殊类型锯齿状腺瘤,以其"长绒毛"的典型特征区别于其他锯齿状病变,异型增生程度重,可能具有更高的恶变潜能。     

凋亡酶激活因子与p53及Ki-67在结直肠癌和结直肠腺癌组织中的表达

目的探讨凋亡酶激活因子1（Apaf-1）、p53和Ki-67在结直肠腺瘤、结直肠癌组织中的表达情况。方法采用SP染色法,检测结直肠癌、腺瘤组织中Apaf-1、p53和Ki-67的表达情况。结果结直肠癌淋巴结转移组中,Apaf-1、p53、Ki-67阳性表达率分别为22.7%、31.8%和90.9%,无淋巴结转移组分别为43.6%、89.7%和61.5%,差异均有统计学意义（均P〈0.05）。结直肠癌A、B期的Apaf-1、p53、Ki-67阳性表达率分别为43.6%、89.7%和61.5%,C、D期的Apaf-1、p53、Ki-67阳性表达率分别为27.7%、31.8%和90.9%。结直肠癌组织中Apaf-1阳性率（39.0%）低于腺瘤（88.0%）,p53阳性率（77.0%）和Ki-67阳性率（68.0%）均高于腺瘤（分别为49.0%、26.0%）,差异均有统计学意义（P〈0.05）。Apaf-1阳性表达与p53、Ki-67阳性表达均呈负相关（r1=-0.358,r2=-0.361,P〈0.01）。结论 Apaf-1、p53与Ki-67表达在结直肠癌、腺瘤的发生、发展与转移过程中有一定影响,对诊断结直肠癌有重要意义。     

p53和Ki67在结直肠癌中的表达及其临床意义

目的探讨p53蛋白、Ki67在结直肠管状腺瘤和结直肠癌中的表达及意义。方法采用免疫组化法分别对71例结直肠癌,16例结肠腺瘤,进行了p53蛋白和Ki67的检测。结果①结直肠癌组织中p53蛋白、Ki67的阳性表达率分别为40.85%(29/71)、77.46%(55/71),均显著高于腺瘤组织,差异均有统计学意义(P=0.019,P=0.000)。②在结直肠癌组织中p53蛋白的阳性表达与结直肠癌的临床分期、浸润深度、组织学分化程度和淋巴结转移有关(P<0.05);结直肠癌中Ki67的表达阳性率与结直肠癌的临床分期和浸润深度有关(P<0.05),与组织学分化程度和淋巴结转移无关(P>0.05)。③p53蛋白和Ki67共同阳性者26例,共同阴性者13例,相关性分析显示,两者之间呈正相关(γ=0.508,P=0.000)。结论 p53蛋白和Ki67在结直肠癌中的表达明显升高,可作为判断结直肠癌恶性程度及预后的重要参考指标。     

垂体腺瘤p53基因Ki-67细胞增生抗原的表达及其临床意义

目的探讨垂体腺瘤p53基因和Ki-67细胞增生抗原表达的变化与肿瘤侵袭行为、肿瘤复发的相关性。方法经手术切除的垂体腺瘤标本67例,按影像学显示的肿瘤大小分为A,B两组(<2.5cm为A组,>2.5cm为B组),用免疫组化方法分别检测p35基因与Ki-67的表达,临床随访1￣3年,观察肿瘤复发情况。结果A组39例中p53阴性11例,低表达28例,Ki-67均为低表达,3年内肿瘤复发4例;B组26例(达到侵袭性标准),p53均显示高表达,Ki-67中度表达10例,高表达16例,其中11例肿瘤3年内复发,两组比较有显著差异(P<0.05)。结论垂体腺瘤的p53和Ki-67的表达与肿瘤的侵袭性呈正相关,而Ki-67的高表达还与肿瘤的复发有关。     

Ki-67、p53及HER-2在结直肠癌组织中表达的临床意义

目的:了解Ki-67、p53及HER-2在结直癌组织中表达的临床意义.方法:采用免疫组化法,观察Ki-67、p53、HER-2在39例结直肠癌组织中的表达特点,并与Dukes分期、组织分化等临床病理特征进行研究探讨.结果:Ki-67、p53及HER-2在结直肠癌组织中的阳性表达率分别为82.1％、56.4％及10.3％;在结直肠癌中,Ki-67在年龄大小和有无淋巴结转移表达中有显著差异(P＜0.05);p53和HER-2在患者性别、年龄、部位、分化程度、Dukes分期、淋巴结转移表达无明显差异(P＞0.05);结直肠腺癌组织中Ki-67与p53的表达呈正相关.结论:联合检测Ki-67和p53在结直肠腺癌中的表达有利于对结直肠腺癌恶性程度及患者预后进评估;而HER-2基因在结直肠肿瘤的表达及相关性治疗,仍需要进一步研究、探讨及验证.     

BRAF和EphB2在人结直肠锯齿状腺瘤中的表达及意义

目的:探讨鼠类肉瘤滤过性病毒致癌基因同源体B1(v-raf murine sarcoma viral oncogene homolog B1,BRAF)和生促红素人肝细胞蛋白(erythropoietin-producing hepatoma cell line B2,EphB2)在人结直肠锯齿状腺瘤中的表达及其意义。方法:收集滨州医学院附属医院1996年1月至2008年5月10例正常结直肠肠黏膜、21例增生性息肉、22例锯齿状腺瘤、55例腺瘤性息肉(18例管状腺瘤、16例管状绒毛状腺瘤、21例绒毛状腺瘤)石蜡标本。免疫组织化学法检测BRAF和EphB2蛋白的表达量,同时观察蛋白的表达部位。结果:增生性息肉中BRAF蛋白阳性细胞多位于隐窝中下区域,腺瘤性息肉的阳性细胞多表达位于隐窝上部区域,而锯齿状腺瘤阳性细胞多表达于隐窝全层。锯齿状腺瘤与腺瘤性息肉的BRAF蛋白表达量相近[(0.129±0.030)vs(0.130±0.026),P>0.05],但远高于增生性息肉[(0.129±0.030)vs(0.102±0.014),P<0.01];锯齿状腺瘤、管状腺瘤、管状绒毛状腺瘤、绒毛状腺瘤之间BRAF蛋白表达量差异无统计学意义[(0.129±0.030)vs(0.116±0.019),(0.119±0.037),(0.122±0.008),P>0.05]。增生性息肉中EphB2蛋白阳性细胞多位于隐窝中下区域细胞膜上,腺瘤性息肉EphB2蛋白阳性细胞位于隐窝上部,而锯齿状腺瘤EphB2蛋白阳性细胞表达于隐窝全层。锯齿状腺瘤与腺瘤性息肉的EphB2蛋白表达量相近[(0.138±0.024)vs(0.139±0.025),P>0.05],而远高于增生性息肉[(0.138±0.024)vs(0.169±0.018),P<0.01];锯齿状腺瘤与管状腺瘤、管状绒毛状腺瘤、绒毛状腺瘤间EphB2蛋白表达量无区别[(0.138±0.024)vs(0.143±0.027),(0.139±0.028),(0.133±0.021),P>0.05]。结论:BRAF和EphB2蛋白在增生性息肉、腺瘤性息肉中隐窝部分区域表达,而在锯齿状腺瘤中隐窝全层表达,提示锯齿状腺瘤是一类独立的不同于腺瘤性息肉的结直肠肿瘤。     

结直肠腺瘤CD133和p53表达及其临床病理意义

目的:探讨CD133蛋白和p53蛋白在结直肠腺瘤组织中的表达及其临床病理学意义。方法:运用免疫组化PV9000二步法检测CD133及p53在172例结直肠腺瘤及正常黏膜组织中的表达。结果:结直肠腺瘤CD133和p53的阳性率分别为40.7%和21.5%。CD133和p53的表达均与肿瘤的大小、病变程度及肿瘤组织学分型有关,P值均<0.05。CD133和p53在结直肠腺瘤中的表达呈正相关,r=0.344,P<0.05。CD133及p53在腺瘤组织中表达明显高于正常黏膜组织,P<0.05。结论:CD133及p53在结直肠腺瘤的发生发展中起着重要作用,可能成为临床新的辅助诊断和监测预后的指标。     

E-cadherin和Ki-67在结直肠癌组织中的表达及意义

 目的 探讨E-cadherin和Ki-67在结直肠癌中的表达及意义。方法 应用免疫组化SP法检测48例结直肠癌、23例结肠腺瘤和20例正常结肠组织中E-cadherin及Ki-67的表达,并分析其与结直肠癌临床病理特征的关系。结果 结直肠癌、结肠腺瘤和正常结肠组织中E-cadherin异常表达率分别为77.1%、24.0%和5.0%,结直肠癌E-cadherin异常表达率明显高于结肠腺瘤和正常结肠组织,组间比较差异有显著性（P〈0.01）。Ki-67阳性指数在结直肠癌、结肠腺瘤及正常结肠组织中分别为（67.60±2.52）%、（38.44±3.59）%及（8.65±1.10）%。结直肠癌的Ki-67阳性指数明显高于结肠腺瘤和正常结肠组织,组间两两比较差异有统计学意义（P〈0.01）。E-cadherin表达与浸润深度和有无淋巴转移有关（P=0.020和P=0.013）,而与患者的年龄、性别、大体形态、分化程度无关。Ki-67表达与患者性别和有无淋巴转移有关（P=0.011和P=0.043）,而与患者的年龄、大体形态、分化程度、浸润深度无关。E-cadherin正常表达组和异常表达组的Ki-67阳性指数分别为（67.30±18.87）%和（68.64±11.99）%。E-cadherin异常表达组Ki-67阳性指数略高于正常表达组,但无统计学意义。结论 E-cadherin和Ki-67是结直肠癌发生发展过程中的重要因子,并与结直肠癌浸润转移有关,可作为评估结直肠癌预后、指导治疗的指标,但两者在结直肠癌发生、发展、侵袭和转移过程中没有协同作用。     

结直肠肿瘤中端粒酶活性表达及其意义

目的观察端粒酶活性表达与结直肠癌发生及预后的关系。方法应用免疫组织化学法检测48例结直肠癌、19例结直肠腺瘤和11例癌旁正常组织中端粒酶的活性表达,并用统计学方法分析其与结直肠癌临床病理因素间的关系。结果端粒酶在结直肠癌中的阳性率为87.5%,明显高于在19例结直肠腺瘤中的阳性率26.3%（5/19）（P＜0.05）和11例癌旁正常组织中的阳性率0.0%（0/11）（P＜0.01）;且与结直肠癌组织病理学分级、淋巴结转移和临床分期关系密切（P＜0.05）。结论端粒酶表达与结直肠癌的发生呈高度正相关,检测标本中端粒酶活性表达有助于结直肠癌患者的预后评估。     

Three-dimensional Reconstruction and Fractal Geometric Analysis of Serrated Adenoma

Serrated adenoma (SA) is a relatively newly defined entity of colorectal neoplasm first characterized by Longacre and Fenoglio-Preiser in 1990. This lesion is characterized by a complicated serrated edge of crypts. In this study, we performed three-dimensional (3-D) reconstruction, including 3-D distribution patterns of Ki-67-positive cells and fractal dimension of SA, in order to evaluate the nature of the complicated architecture, including its possible morphogenesis. We studied nine colonoscopic polypectomy specimens including three SAs, three tubular adenomas (TAs), and three hyperplastic polyps (HPs). Sixty serial tissue sections per case were stained alternately with hematoxylin and eosin (H&E) and Ki-67 immunostain. Each serial image was then digitized for 3-D computer analysis and the distribution pattern of Ki-67-positive cells was evaluated. Ki-67-immunostained sections were also subjected to 2-D quantitative morphometric study. In addition, the fractal dimensions of images from H&E-stained sections were examined using a box-counting method. Results of the 3-D reconstruction study demonstrated that glandular budding and branching were more frequent in SA than in TA or HP. These findings were confirmed quantitatively by the results of fractal geometric analysis of these polyps (fractal dimension:1.34±0.08 for SA, 1.23±0.07 for TA, and 1.28±0.12 for HP). Ki-67-positive cells in HP were localized mainly in the bottom of crypts and those in TA were diffusely distributed, while Ki-67-positive cells in SA were mainly aggregated in the depressed sites of serrated epithelia. These findings were also confirmed quantitatively using 2-D morphometry. These distribution patterns of the proliferative zone of SA are considered to contribute to the formation of the characteristic serrated epithelia and the complicated morphological appearance of SA.     

Three-dimensional reconstruction and fractal geometric analysis of serrated adenoma.

Serrated adenoma (SA) is a relatively newly defined entity of colorectal neoplasm first characterized by Longacre and Fenoglio-Preiser in 1990. This lesion is characterized by a complicated serrated edge of crypts. In this study, we performed three-dimensional (3-D) reconstruction, including 3-D distribution patterns of Ki-67-positive cells and fractal dimension of SA, in order to evaluate the nature of the complicated architecture, including its possible morphogenesis. We studied nine colonoscopic polypectomy specimens including three SAs, three tubular adenomas (TAs), and three hyperplastic polyps (HPs). Sixty serial tissue sections per case were stained alternately with hematoxylin and eosin (H&E) and Ki-67 immunostain. Each serial image was then digitized for 3-D computer analysis and the distribution pattern of Ki-67-positive cells was evaluated. Ki-67-immunostained sections were also subjected to 2-D quantitative morphometric study. In addition, the fractal dimensions of images from H&E-stained sections were examined using a box-counting method. Results of the 3-D reconstruction study demonstrated that glandular budding and branching were more frequent in SA than in TA or HP. These findings were confirmed quantitatively by the results of fractal geometric analysis of these polyps (fractal dimension:1.34 +/- 0.08 for SA, 1.23 +/- 0.07 for TA, and 1.28 +/- 0.12 for HP). Ki-67-positive cells in HP were localized mainly in the bottom of crypts and those in TA were diffusely distributed, while Ki-67-positive cells in SA were mainly aggregated in the depressed sites of serrated epithelia. These findings were also confirmed quantitatively using 2-D morphometry. These distribution patterns of the proliferative zone of SA are considered to contribute to the formation of the characteristic serrated epithelia and the complicated morphological appearance of SA.     

MUC1 expression in intramucosal colorectal neoplasms. Possible involvement in histogenesis and progression

PURPOSE: The mucin core peptide MUC1 often is detectable in colorectal carcinoma (CRC) tissue and cell lines. However, whether MUC1 in CRC correlates with tumor histogenesis and progression is unclear. We studied the relationship between MUC1 expression in intramucosal CRC and clinicopathologic features, expression of Ki-67, and p53 protein, and apoptosis. METHODS: The intramucosal CRC we studied included 140 endoscopically or surgically resected lesions, including 106 low-grade carcinomas and 34 high-grade carcinomas. De novo carcinoma, defined as carcinoma with no adenomatous component, represented 9 of 140 tumors. Three macroscopic types were identified: 57 lesions were polypoid, 55 were superficial and flat, and 28 were granular-type laterally spreading tumors (G-LST). MUC1, Ki-67, and p53 expression were examined immunohistochemically. Apoptotic cells were identified by in situ DNA nick end labeling. RESULTS: MUC1 expression in high-grade carcinomas was significantly more frequent (p < 0.01) than in low-grade carcinomas; expression in adenomas was almost nil. MUC1 expression in polypoid carcinomas was significantly more frequent (p < 0.05) than in superficial carcinomas or G-LST. MUC1 expression in carcinomas with p53 expression was significantly more frequent (p < 0.01) than in carcinomas not expressing p53. No significant correlation was found between expression of MUC1 and Ki-67 labeling index. MUC1 was expressed more frequently in carcinomas with relatively high apoptotic index (p < 0.01). MUC1 expression did not differ between de novo carcinomas and those developing from adenomas. CONCLUSIONS: The results suggest that MUC1 is likely to be expressed in the course of colorectal carcinoma development when p53 protein is overexpressed and apoptosis is prominent.     

自身配对的锯齿状腺瘤与传统腺瘤临床病理特征的比较

目的探讨锯齿状腺瘤与传统腺瘤的癌变潜能的差异。方法 2007年4月～2009年9月经肠镜检出、并经病理检查证实、同时具有锯齿状腺瘤、管状腺瘤的病例。从腺瘤的临床特征（生长部位、直径大小、蒂部情况及异型增生程度）及免疫组化（β-连环蛋白、P53、Ki67）两个方面,比较两者差异。结果同时具有SA及TA的16例,男性13例,女性3例,年龄43～81岁,平均年龄62.9岁;2种腺瘤的部位分布、异型增生程度及直径大小无显著性差异,无蒂的SA明显多于TA,差异有统计学意义（P〈0.05）;β-连环蛋白、P53、Ki67在2种腺瘤中表达水平无显著差异。结论同1个体的锯齿状腺瘤与传统腺瘤的临床病理特征无显著性差异。     

结直肠腺瘤OD133和p53表达及其临床病理意义

目的：探讨CD133蛋白和p53蛋白在结直肠腺瘤组织中的表达及其临床病理学意义。方法：运用免疫组化PV9000二步法检测CD133及p53在172例结直肠腺瘤及正常黏膜组织中的表达。结果：结直肠腺瘤CD133和p53的阳性率分别为40．7％和21．5％。CD133和p53的表达均与肿瘤的大小、病变程度及肿瘤组织学分型有关,P值均〈0．05。CD133和p53在结直肠腺瘤中的表达呈正相关,r=0．344,P〈0．05。CD133及p53在腺瘤组织中表达明显高于正常黏膜组织,P〈0．05。结论：CD133及p53在结直肠腺瘤的发生发展中起着重要作用,可能成为临床新的辅助诊断和监测预后的指标。     

Expression of p53, Ki-67 and Bcl-2 in parathyroid adenoma and residual normal tissue

The aim of this study was to investigate the expression of Ki-67, bcl-2 and p53 in parathyroid adenomas and their residual rim of normal parathyroid tissue. Specimens from 26 parathyroid adenomas were studied by immunohistochemical analysis for Ki-67, bcl-2 and p53 expression. Positive findings were noted for p53 in 4 (15%) adenomas and none of the residual rims of normal parathyroid tissue (p = 0.055); for Ki-67 in 15 (56%) adenomas and none of the residual rims of normal parathyroid tissue (p = 0.00002); and for bcl-2 in 19 (73%) adenomas and 8 (31%) residual rims of normal parathyroid tissue (p < 0.01). The high rate of Ki-67 expression may indicate susceptibility of parathyroid adenomas to clonal proliferation. The weak immunoreactive expression of p53, combined with a relatively strong expression of bcl-2, may contribute to the characteristic slow progression of these tumors.     

Expression of P53, P27 and KI-67 in colorectal cancer patients of various ethnic origins: clinical and tissue microarray based analysis

BACKGROUND: This study was conducted to determine survival according to the expression of molecular markers in colorectal cancer (CRC) patients of various ethnic origins. METHODS: Resection of primary tumor was conducted on 171 patients with CRC. Corresponding archived paraffin-embedded blocks were retrieved and tissue microarray (TMA) constructed. Immunohistochemical staining of the TMA for p53, p27 and Ki-67 was quantified by two independent pathologists. Survival was analyzed using the Kaplan-Meier product limit method. RESULTS: With a median follow-up of 65 months, 56 patients (32.7%) died of disease. AJCC stage correlated with disease-free (DFS, P < 0.0001) and overall survival (OS, P < 0.0001). IHC staining was positive for Ki-67 in 77.4%, p53 in 55.8% and p27 in 54.2% of patients. Primary tumor marker expression did not correlate with DFS or OS. The 5-year DFS for Ashkenazi Jews was 75%, significantly higher than Sephardic Jews (SJ) 64% and Palestinian Arabs (PA) 38%, P = 0.001. CONCLUSIONS: Ethnicity among Ashkenazi and SJ and PA appears to have a significant impact on disease outcome in patients with CRC patients, while primary tumor expression of p53, p27 and Ki-67 was unrelated to disease outcome.     

大肠腺瘤癌变过程中β-catenin、p53和增殖细胞核抗原表达的研究

目的 探讨β－catenin、p53和增朱（PCNA）在大肠腺瘤癌变中的可能作用。方法 以免疫组织化学方法检测77例大肠腺瘤（CRA）及癌变组织中β－catenin、p53蛋白及PCNA的表达情况。结果 CRA随上皮不典型增生程度的提高以及癌变的出现,β－catenin异常表达率逐渐增高（P＜0.05）。伴中、重度上皮不典型增生的CRA和CRA癌变的出现,β－catenin核表达阳性率均明显高于上皮轻度不典型增生的CRA（P＜0.01）。CRA伴轻度不典型增生和CRA伴中、重度不典型一及CAR癌变3组的p53蛋白和PCNA表达依次增高,其阳性率分别为10.3%、43.8%、75.0%和17.2%、62.5%、87.5%。在β－catenin核表达阳性者中,其PCNA的强阳性表达率明显高于β－catenin核表达阴性者（69.7%和36.4%,P＜0.05）;在p53蛋白表达阳性者中,其PCNA的强阳性表达率明显高于p53表达阳性者（72.4%和37.5%,P＜0.05）。在CRA癌变组中,有50.0%可见β－catenin和p53同时表达。结论 β－catenin、p53和PCNA在CRA癌变过程中可能发挥了重要作用。     

Depressed adenoma of the duodenum in patients with familial adenomatous polyposis: endoscopic and immunohistochemical features.

BACKGROUND: Depressed neoplastic lesions of the colorectum have been specified in patients with familial adenomatous polyposis (FAP). The aim of this study was to characterize endoscopic, histologic, and immunohistochemical features of depressed adenoma of the duodenum in patients with FAP. METHODS: Duodenoscopy was performed on 25 patients with FAP, and the neoplastic nonampullary lesions were classified as polypoid or depressed adenomas. The grade of dysplasia, the proliferative activity determined by Ki-67 labeling index (LI), and the grade of p53 expression were compared between polypoid and depressed neoplasia. RESULTS: Ten subjects had depressed nonampullary adenoma, whereas polypoid adenoma was found in the remaining 15 subjects. Moderate dysplasia was more frequent in depressed adenoma than in polypoid adenoma (70% vs. 27%, P = 0.04). Whereas p53 expression was not different between the two adenoma groups, the LI was significantly higher in depressed adenoma than in polypoid adenoma (59.7 +/- 9.5 vs. 47.5 +/- 10.7, P < 0.01). CONCLUSIONS: Depressed adenoma of the duodenum is a distinctive phenotype of duodenal neoplasm in patients with FAP. The high proliferative activity of depressed adenoma suggests that there may be a need to survey FAP patients with such lesions intensively.     

Expression of survivin correlates with apoptosis, proliferation, and angiogenesis during human colorectal tumorigenesis

BACKGROUND: To identify the role of survivin, a novel inhibitor of apoptosis (IAP) in colorectal tumorigenesis, the authors investigated tissue expression of survivin in human colorectal tumors including 43 hyperplastic polyps, 171 adenomas with low dysplasia, 42 adenomas with high dysplasia, and 60 carcinomas in adenoma, and examined whether the expression of survivin correlated with tumor cell apoptosis, proliferation, and angiogenesis, which is known to initiate the imbalance between cell proliferation and apoptosis. METHODS: Immunohistochemical staining for the paraffin sections by using the monoclonal antibodies, survivin, p53, bcl-2, Ki-67, and CD34, was performed by the standard avidin-biotin-peroxidase technique. The apoptotic cells were detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling method, using an Apop Tag in situ detection kit. RESULTS: The immunoreactivity of survivin significantly increased in the transition from adenoma with low dysplasia to high dysplasia/carcinoma (P < 0.001). Similar changes in protein expression were observed for p53 but not for bcl-2, which was expressed throughout the colorectal tumorigenesis. This transition was associated with a significant decrease in the apoptotic index (AI) and significant increases in the Ki-67 labeling index (LI) and microvessel density (MVD; P < 0.001 for both). The expression of survivin inversely correlated with AI and was positively correlated with Ki-67 LI and MVD (P < 0.001 for both). CONCLUSIONS: These results suggest that, like p53, survivin plays an important role in transition from adenoma with low dysplasia to high dysplasia during human colorectal tumorigenesis.