Notch3在肾透明细胞癌中的表达及临床意义

目的:通过研究Notch3蛋白在肾透明细胞癌组织和癌旁组织中的表达变化情况,探讨其临床意义及相关影响因素。方法:采用免疫组织化学染色检测57例肾透明细胞癌组织、38例癌组织外缘1.0 cm处组织中的Notch3蛋白表达情况,并观察其与临床病理参数之间的关系。结果:肾透明细胞癌、癌旁组织中Notch3蛋白的阳性表达率分别为80.7%（46/57）、31.6%（12/38）,P＜0.05。单因素分析表明,Notch3蛋白的表达与肾透明细胞癌的临床分期、病理学分级、远处转移密切相关（P＜0.05）。多因素分析表明,患者的年龄、临床分期、吸烟史是Notch3蛋白在肾透明细胞癌中表达的独立危险因素（P＜0.05）。结论:Notch3蛋白在肾透明细胞癌组织中的表达明显增高,Notch3可能成为肾透明细胞癌的潜在基因治疗靶点和早期诊断检测及预防的指标之一。     

Rsf-1在非小细胞肺癌中的表达及意义

目的:分析Rsf-1在非小细胞肺癌中的表达及与临床病理因素的关系.方法:应用Real-time PCR和免疫组化法检测非小细胞肺癌中Rsf-1的mRNA及蛋白表达情况.结果:有84％(21/25)肺癌组织病例中Rsf-1的mRNA含量明显高于对应的正常肺组织(P＜0.001),肿瘤组织中Rsf-1的mRNA平均值是其癌旁正常肺组织均值的2.37倍.免疫组化结果显示68.4％ (67/98)病例存在Rsf-1蛋白过表达,其过表达与肺癌患者的年龄、性别、肿瘤类型、原发肿瘤分级和淋巴结转移等未发现明显的相关性,而与肺癌的低分化和高p-TNM分期呈正相关(P=0.001;P=0.020).结论:肺癌中存在Rsf-1基因的扩增和蛋白的高表达,并与低分化和高p-TNM分期相关.     

肾透明细胞癌组织肾母细胞瘤过表达基因表达临床意义的探讨

目的：探讨肾母细胞瘤过表达基因（NOV）对肾透明细胞癌分级、分期、大小、增殖状态和预后的影响。方法：应用免疫组化法检测54例肾透明细胞癌组织NOV蛋白的表达,分析其与肾透明细胞癌分期、分级、大小、Ki-67指数的相关性,并比较NOV阳性组和阴性组的生存率差异。结果：NOV在肾脏透明细胞癌组织中的染色强度明显低于癌旁正常肾组织,22例（100％）癌旁正常肾组织均呈强阳性染色,54例肾癌组织中24例（44．4％）为弱阳性染色,8例（14．8％）为中等阳性染色;癌组织总阳性率（59．3％）亦显著低于癌旁正常肾组织（100％）,P〈0．05。NOV阳性组的Ki-67指数（2．6±1．5）％,明显低于NOV阴性组的（4．2±2．1）％,P〈0．05。NOV表达与肿瘤分期及大小无相关性,P〉0．05。NOV阳性组术后5年特异生存率（82．6％）显著高于阴性组（50．3％）,P〈0．05。结论：NOV对肾透明细胞癌起抑制作用,可作为预后判断的肿瘤标志。     

RhoB在肾透明细胞癌中的表达及临床意义

目的:探讨RhoB在肾透明细胞癌中的表达及临床意义.方法:采用实时定量PCR、Western blot和免疫组化方法检测RhoB在肾透明细胞癌组织中的表达情况.选取60例肾透明细胞癌组织标本,详细收集病人临床病理资料,通过免疫组化方法检测RhoB在肾透明细胞癌组织中的蛋白表达水平,并分析RhoB的蛋白水平与临床病理资料的关系.结果:与对应瘤旁肾组织相比,RhoB的mRNA及蛋白表达水平在肾透明细胞癌组织标本中明显降低;RhoB的蛋白表达水平在不同年龄、性别组间差异无统计学意义(P>0.05),而在肿瘤直径大小、T分期、临床分期和组织分级间差异有显著统计学差异(P<0.05).结论:RhoB的表达降低可能在肾透明细胞癌的肿瘤发生中发挥作用,且其表达下降可能与肾透明细胞癌的恶性进展有关.     

肾透明细胞癌中PCNA和T淋巴细胞的免疫组化研究

应用免疫组化的方法，检测增殖细胞核抗原（ＰＣＮＡ）和Ｔ淋巴细胞在５２例肾透明细胞癌中的阳性表达，结果显示ＰＣＮＡ指数与肿瘤核分级存在相关性，与分期无相关性；ＰＣＮＡ－ＬＩ≥２０％组的生存率明显低于ＰＣＮＡ－ＬＩ＜２０％组（Ｐ＜０．０５）；Ｔ－ＬＩ≥１０％组生存率明显高于Ｔ－ＬＩ＜１０％组（Ｐ＜０．０５）；与肿瘤核分级、分期无相关性。提示ＰＣＮＡ－ＬＩ、Ｔ－ＬＩ可以作为肾透明细胞癌预后的参考指标。     

肾透明细胞癌中血小板衍生生长因子BB和微血管密度的检测及临床意义

目的 探讨肾透明细胞癌中血小板衍生生长因子BB (PDGF-BB)的表达以及CD34标记的微血管密度(MVD)与患者临床病理特征及预后的关系.方法 采用免疫组化SP法,检测CD34和PDGF-BB在100例肾透明细胞癌组织中的表达情况.结果 100例肾透明细胞癌组织中,CD34标记的MVD为(105.49 ±37.95)个／高倍视野.以均数为分界点,将100例肾透明细胞癌分为低MVD组(42例)和高MVD组(58例).低MVD组和高MVD组的MVD分别为(75.12±22.41)个／高倍视野和(135.86±22.91)个／高倍视野,差异有统计学意义(P ＜0.001).肾透明细胞癌的MVD与肿瘤的T分期、病理分级以及术后是否发生转移有关(均P＜0.05).PDGF-BB蛋白低表达38例,高表达62例.肾透明细胞癌中PDGF-BB蛋白的表达与肿瘤直径、T分期、病理分级以及术后是否发生转移有关(均P＜0.05).生存分析结果显示,高MVD和PDGF-BB蛋白高表达的肾透明细胞癌患者的预后明显优于低MVD和PDGF-BB蛋白低表达者(均P＜0.001).相关性分析结果显示,PDGF-BB蛋白在肾透明细胞癌中的表达与MVD呈正相关(r=0.461,P＜0.001).结论 在肾透明细胞癌中,MVD和PDGF-BB蛋白的表达越高,肿瘤的分级和分期越好,患者的生存时间越长.     

Caveolin-1和cyclin D1在肾细胞癌中的表达及其意义

目的 探讨Caveolin-1、cyclin D1在肾细胞癌发生、发展中的作用.方法 采用免疫组化EnVision法检测41例肾细胞癌中Caveolin-1和cyclin D1蛋白的表达,并分析表达情况与病理学分期、病理核分级、肿瘤大小等临床病理参数的关系.结果 Caveolin-1在肾细胞癌中的表达阳性率为41.5％,与肿瘤病理学分期、核分级及患者年龄呈正相关(P＜0.05).cyclin D1在癌组织中表达阳性率为46.3%(高表达),肿瘤周围正常肾组织不表达或低表达,cyclin D1表达与肿瘤体积大小有关,体积小者cyclin D1高表达(P＜0.05).Caveolin-1和cyclin D1两者之间表达无相关性.结论 Caveolin-1和cyclin D1过表达可能在肾细胞癌的生长、分化中发挥重要作用.     

肾透明细胞癌组织中 Notch1的表达及意义

目的:研究Notch1在肾透明细胞癌（clear cell renal cell carcinoma,ccRCC）组织中的表达变化情况,并探讨其相关临床意义。方法:采用免疫组化、实时荧光定量PCR技术检测52例肾透明细胞癌、40例癌旁肾组织中Notch1蛋白和mRNA的表达。结果:肾透明细胞癌及癌旁组织中Notch1蛋白阳性表达率分别为80.8%(42/52)、30.0%(12/40)（P<0.05）;Notch1蛋白表达与肾透明细胞癌的TNM分期、Fuhrman分级、远处转移有关(P<0.05);肾透明细胞癌及癌旁组织中Notch1 mRNA相对表达量分别为0.317±0.044、0.153±0.038（P<0.05）。结论:Notch1蛋白及mRNA在肾透明细胞癌组织中表达明显增高。但在肾透明细胞癌发生、发展过程中的作用仍有待探讨。     

肾透明细胞癌中血管内皮生长因子表达及微血管密度的临床病理研究

目的 探讨肾透明细胞癌中血管内皮生长因子(VEGF)表达及微血管密度(MVD)的临床病理意义.方法 应用免疫组织化学方法检测VEGF蛋白表达,通过CD34抗体标记血管内皮来计算MVD值.结果 66例肾透明细胞癌VEGF蛋白表达阳性率为54.5%(36/66),其表达强弱与肿瘤分级、大小、分期等无显著相关性.MVD值为12～96.3,与肿瘤分级(P=0.005)、分期(P=0.000)相关,分级高、分期晚的透明细胞癌MVD值比分级低、分期早的低.有转移的肾透明细胞癌MVD值低,没有转移者MVD值高,差异有统计学意义(P=0.011).肿瘤体积较大时MVD50的病例(26.7%)明显少于MVD<50的病例(73.3%).VEGF和MVD值均与肾被膜累及情况无关,二者之间亦无相关性.结论 VEGF在肾透明细胞癌中的高表达,使得其可能成为治疗的靶向分子.透明细胞癌中MVD值与分级和分期呈负相关,可能有一定预后意义.     

Vimentin在肾透明细胞癌中的表达及临床意义

目的:探讨波形蛋白(Vimentin)在人肾透明细胞癌(clear cell renal cell carcinoma,ccRCC)和癌旁组织样本中的表达情况,并分析其与 ccRCC 临床分期、病理分级和侵袭转移等恶性生物学特性的关系及临床意义。方法:Western blot方法检测29例新鲜肾透明细胞癌及相应癌旁组织中Vimentin的表达;免疫组织化学方法检测120例肾透明细胞癌及相应癌旁组织中Vimentin的表达情况,分析Vimentin在肾透明细胞癌组织中及癌旁正常肾脏组织中的表达水平差异及Vimentin的表达与肿瘤大小、临床分期、组织病理分级、远处转移的关系。结果:Vimentin在肾透明细胞癌及相应癌旁组织中均有表达,前者的表达水平较后者显著升高（P＜0.01）;免疫组织化学显示肾透明细胞癌组织中,Vimentin的阳性表达率高达90.0%,与癌旁组织存在明显差异（P＜0.01）;Vimentin在肾透明细胞癌组织中以胞膜表达为主,其表达随肾癌的临床分期、肾包膜受侵、癌栓形成或远处转移有升高趋势,但组间比较经统计学分析均无显著性差异。结论:Vimentin在肾透明细胞癌组织中的表达明显高于癌旁正常肾组织,提示Vimentin在肾透明细胞癌的发生发展过程中发挥重要的作用。Vimentin在肾透明细胞癌组织中过表达,与肾癌的发展密切相关,可以作为肾细胞癌早期诊断、预后和复发评估的参考指标之一。     

Dysadherin mRNA在肾透明细胞癌中的表达及其意义

目的探讨Dysadherin在。肾透明细胞癌（RCCC）中的表达情况及其临床意义。方法选取60例新鲜RCCC组织及其癌旁肾组织。患者男35例,女25例;年龄37-78岁,中位年龄61岁;肿块直径〉7cm24例,≤7cm36例;核分级Ⅰ、Ⅱ级39例,Ⅲ、Ⅳ级21例,应用反转录．聚合酶链反应（RT-PCR）及免疫组织化学的方法分别在mRNA及蛋白水平检测Dysadherin的表达情况。结果RCCC组织中Dysadherin mRNA表达水平为2．0043±0．2890,明显高于癌旁肾组织的0．8461±0．2479（t=6．8020,P〈0．05）。Dysadherin在RCCC中的表达与肿瘤的核分级有关,其中核分级为Ⅲ、Ⅳ级的表达量明显高于Ⅰ、Ⅱ级,二者mRNA表达量分别为1．6224±0．3194、2．7780±0．2288（t=6．5750,P〈0．05）,蛋白表达阳性率分别为64．1％（25／39）和95．2％（20／21）（χ^2=5．495,P〈0．05）,而在患者不同性别（t=1．0530,χ^2=0．023）、年龄（t=0．0511,χ^2=0．089）、肿块直径（t=1．0330,χ^2=0．370）之间差异无统计学意义（P〉0．05）。结论Dysadherin的表达随着RCCC肿瘤细胞核分级的升高而升高,可能成为RCCC有价值的预后标志物之一。     

Expression and prognostic roles of beta-catenin in hepatocellular carcinoma: correlation with tumor progression and postoperative survival.

PURPOSE: Although hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the human liver, the molecular changes and mechanisms that regulate its development and progression remain unclear. In the present study, we investigated the correlation between beta-catenin expression and clinical outcome in 51 patients with relatively small (maximal diameter < 30 mm), solitary HCCs. EXPERIMENTAL DESIGN: The tumors were classified according to histological tumor differentiation (grade I, 11 tumors; grade II, 28 tumors; grade III, 12 tumors). Using immunohistochemical methods to detect nuclear accumulation of beta-catenin, we investigated the correlation between beta-catenin expression and clinical outcome and compared the correlation with cyclin D1, Ki-67, and E-cadherin. RESULTS: Focal or generalized nuclear beta-catenin expression was observed in 36.4% (4 of 11) of the grade I tumors, 39.3% (11 of 28) of the grade II tumors, and 25% (3 of 12) of the grade III tumors. Nuclear beta-catenin-positive grade III tumors were associated with significantly poorer survival (P = 0.004), whereas none of the patients with nuclear beta-catenin-negative grade I tumors died. With regard to proliferative activity, positive nuclear beta-catenin staining correlated significantly with an increased Ki-67 labeling index in grade I (P < 0.0001) and grade III (P = 0.0045) tumors and with reduced epithelial cadherin expression in the cell membrane (P < 0.001). In contrast, no association with the expression of cyclin D1, one of the target factors of beta-catenin, was detected. CONCLUSIONS: Our present data suggest that beta-catenin plays important roles in promoting tumor progression by stimulating tumor cell proliferation and reducing the activity of cell adhesion systems and is associated with a poor prognosis, especially in patients with poorly differentiated HCCs.     

Expression of tenascin-C in various human brain tumors and its relevance for survival in patients with astrocytoma

BACKGROUND: Tenascin-C (TN-C), a large extracellular matrix (ECM) glycoprotein with a molecular weight of 180-250 kilodaltons, is present in several normal adult tissues. TN-C is up-regulated during embryogenesis, in wound healing, and in tumor tissues. Glioblastoma multiforme (GBM) is the most frequent and malignant astrocytic tumor comprised of poorly differentiated, neoplastic astrocytes. Recently, TN-C-based radioimmunotherapy was administered to patients with GBM. METHODS: In the current study, the authors used immunohistochemistry to conduct a systematic investigation of TN-C distribution patterns in normal human brain tissue and in a large variety of brain tumors (n = 485 tumors). Immunoreactivity for TN-C was assessed with regard to its localization within tumor cells, blood vessels, and ECM using three different monoclonal antibodies (clones BC2, BC4, and TN2). RESULTS: In control human brains, a significant difference was noted in the expression of TN-C when comparing gray with white matter using either Western blot analysis or immunohistochemistry. TN-C was found in the white matter of the frontal, temporal, parietal, and occipital lobes and in the hippocampus, where the immunoreaction was especially strong in the hippocampal formation. In 181 astrocytomas of different grades (World Health Organization [WHO] Grade 2-4), TN-C immunopositivity was seen to varying degrees in the cellular and stromal components of the tumor and in tumor-associated vessels. Glioblastomas (n = 113 tumors) showed strong immunopositivity in the vessels and moderate immunopositivity of the ECM. A statistically significant reduction of TN-C immunopositivity in tumor-associated vessels or ECM was observed in anaplastic astrocytomas (WHO Grade 3) compared with GBM (WHO Grade 4). A Kaplan-Meier analysis showed that patients who had GBM lesions that lacked TN-C immunopositivity in the ECM had a significantly longer survival (median, 28 months; standard error, 7.8 months) (n = 12 patients) compared with patients who had GBM lesions with TN-C immunopositivity (median, 12 months; standard error, 1.6 months) (n = 87 patients). In meningiomas (n = 24 tumors), the neoplastic cells, the ECM of the tumor, and the vessels were TN-C negative. In schwannomas (n = 31 tumors), the tumor cells were TN-C negative; whereas, in > 50% of tumors, the vessels and the ECM of regressively altered tumor areas were positive. In metastatic carcinomas (n = 53 tumors), the tumor cells were negative; seldom were vessels stained positive for TN-C. Focal areas of the ECM, often accompanied with fibrotic changes, were immunopositive for TN-C. CONCLUSIONS: The most constant TN-C immunopositivity was noted in the ECM of the fibrotic stroma in highly malignant brain tumors and along the tumor border, especially in high-grade astrocytomas. The current results suggest that TN-C expression may be correlated with the grade of malignancy in astrocytic tumors and that the presence or absence of TN-C expression in the stroma of astrocytic tumors may play a not yet clearly understood role in shortening or prolonging, respectively, the survival of patients.     

Molecular determinants of tumor differentiation in papillary serous ovarian carcinoma

In epithelial ovarian cancer, tumor grade is an independent prognosticator whose molecular determinants remain unknown. We investigated patterns of gene expression in well- and poorly differentiated serous papillary ovarian and peritoneal carcinomas with cDNA microarrays. A 6500-feature cDNA microarray was used for comparison of the molecular profiles of eight grade III and four grade I stage III serous papillary adenocarcinomas. With a modified F-test in conjunction with random permutations, 99 genes whose expression was significantly different between grade I and grade III tumors were identified (P < 0.01). A disproportionate number of these differentially expressed genes were located on the chromosomal regions 20q13 and all exhibited higher expression in grade III tumors. Interphase fluorescent in situ hybridization demonstrated 20q13 amplification in two of the four grade III and none of the three grade I tumors available for evaluation. Several centrosome-related genes also showed higher expression in grade III tumors. We propose a model in which tumor differentiation is inversely correlated with the overexpression of several oncogenes located on 20q13, a common amplicon in ovarian and numerous other cancers. Dysregulation of centrosome function is one potential mechanistic link between genetic/epigenetic changes and the poorly differentiated phenotype in ovarian cancer.     

TN-C和Ki-67的表达与非小细胞肺癌临床病理特征的相关性

目的探讨TN-C和Ki-67蛋白在非小细胞肺癌组织中的表达及其与非小细胞肺癌临床特征的相关性。方法选择459例非小细胞肺癌患者的肿瘤组织样本,免疫组化检测组织中TN-C和Ki-67的表达,计算其阳性率,并进一步分析二者的表达与非小细胞肺癌临床病理特征的相关性。结果(1)TN-C在不同性别、年龄、组织学类型、分化程度以及肿瘤位置的非小细胞肺癌组织中阳性表达差异无统计学意义(P>0.05);而与非淋巴结转移、肿瘤直径<3 cm、Ⅰ~Ⅱ期患者相比,淋巴结转移、肿瘤直径≥3 cm、Ⅲ~Ⅳ期患者TN-C阳性表达率显著升高(P<0.05)。(2)Ki-67在不同性别、年龄、肿瘤位置、淋巴结转移以及肿瘤直径的非小细胞肺癌组织中阳性表达差异无统计学意义(P>0.05);而与鳞癌、中高分化及Ⅰ~Ⅱ期患者相比,腺癌、低分化、Ⅲ~Ⅳ期患者Ki-67阳性表达率显著升高(P<0.05)。(3)TN-C表达阳性率与非小细胞肺癌患者淋巴结转移、肿瘤直径以及TMN分期均呈正显著相关性(γ>0,P<0.05),Ki-67表达阳性率与非小细胞肺癌患者分化程度和TMN分期均呈正显著相关性(γ>0,P<0.05)。结论TN-C和Ki-67的表达均与非小细胞肺癌的发生、进展等密切相关,可作为该肿瘤临床诊治的病理学依据。     

MTA1 overexpression correlates significantly with tumor grade and angiogenesis in human breast cancers

Metastasis associated antigen 1 (MTA1) is a recently identified candidate metastasis-associated gene that plays an important role in tumorigenesis and tumor aggressiveness, especially tumor invasiveness and metastasis. We analyzed the relationship between MTA1 expression and variable clinicopathological features and characterized its role in tumor angiogenesis in human breast cancers. Two hundred and sixty-three breast cancer cases that successfully underwent surgery at Hanyang University Hospital (Seoul, Korea) between January 1989 and December 1997 were enrolled. MTA1 expression was observed by immunohistochemical staining and correlated with intratumoral microvessel density (MVD) and other clinicopathological parameters. MTA1 overexpression correlated significantly with higher tumor grade (grades 1 and 2 vs grade 3, P = 0.009). However, MTA1 expression did not correlate with tumor stage, status of estrogen and progesterone receptors, or axillary lymph node metastasis. Interestingly, MTA1 expression was found to correlate significantly with tumor MVD (P = 0.002). Survival analysis did not show a significant difference between MTA1 overexpression and poorer survival. In conclusion, MTA1 overexpression was found to be closely associated with higher tumor grade and increased tumor angiogenesis. These findings suggest MTA1 as a predictor of aggressive phenotype and a possible target molecule for anti-angiogenic drugs in breast cancer treatment.     

Overexpression of TGF-beta1 in esophageal (Barrett's) adenocarcinoma is associated with advanced stage of disease and poor prognosis

Expression of TGF-beta1, a major member of the TGF-beta superfamily and important promoter of tumor growth, was investigated in a series of primary resected esophageal (Barrett's) adenocarcinomas to establish its potential clinical significance and prognostic relevance in this entity. A series of 123 primary resected adenocarcinomas of the distal esophagus, arising in association with Barrett's esophagus, and corresponding normal squamous epithelium (n = 12) and non-malignant Barrett's mucosa (n = 11), were investigated by means of quantitative RT-PCR for expression of TGF-beta1, using paraffin embedded tissue samples. Gene expression levels were correlated with clinical parameters and overall survival. TGF-beta1 mRNA was expressed in all tumors, but relative gene expression levels varied largely among different tumors. The relative gene expression was significantly higher in tumor tissue compared to squamous epithelium (P = 0.005) and Barrett's mucosa (P=0.002), expressing only low amounts of TGF-beta1. Relative overexpression of the TGF-beta1 gene was associated with advanced UICC stage (III/IV vs. I/II; P = 0.009), depth of tumor infiltration (pT3 vs. pT1/2; P < 0.001), nodal involvement (pN1 vs. pN0; P = 0.006), and lymphatic vessel invasion (L1 vs. L0; P = 0.011). On univariate survival analysis, TGF-beta1 overexpression had a significant negative impact on survival (log rank test; P = 0.0255). However, the prognostic impact was not independent from other strong predictors of survival (pT, pN) on multivariate survival analysis. Our data show that TGF-beta1 overexpression is associated with advanced stage of esophageal adenocarcinoma and implies a negative impact on survival. The TGF-beta pathway may be a potential target for molecular therapies of advanced tumors of this entity.     

Osteopontin expression correlates with prognostic variables and survival in clear cell renal cell carcinoma

BACKGROUND AND OBJECTIVES: Osteopontin (OPN) is a phosphorylated glycoprotein with diverse functions including tumorigenesis and tumor cell metastasis. Recently, it has been detected in a growing number of human tumors, and assessed as a potential prognostic marker. The aim of this study was to analyze the expression of OPN in normal renal tissue and clear cell renal cell carcinomas (CRCCs), and to assess its prognostic significance. METHODS: The expression of OPN protein was immunohistochemically analyzed in 171 CRCCs and compared to usual clinicopathological parameters such as tumor size, nuclear grade, pathological stage, Ki-67 proliferation index, and cancer-specific survival. RESULTS: In normal renal parenchyma, the expression of OPN was seen in distal tubular epithelial cells, calcifications, and some stromal cells. The upregulation of OPN was observed in 61 CRCCs (35.7%) in the form of cytoplasmic granular staining of various intensities. Statistical analysis showed correlation of the OPN expression with tumor size (P < 0.001), Fuhrman nuclear grade (P < 0.001), pathological stage (P = 0.011), and Ki-67 proliferation index (P < 0.001). Moreover, patients with OPN-positive tumors had significantly worse prognosis in comparison to patients with tumors lacking OPN protein (P = 0.004). CONCLUSION: Our results suggest that overexpression of OPN is involved in the progression of CRCC.     

Prognostic significance of p27(kip-1) expression in colorectal adenocarcinomas is associated with tumor stage.

PURPOSE: Although the decreased expression of p27(kip-1), a cyclin-dependent kinase inhibitor, has been correlated with advanced tumor stage and short survival of patients with colorectal adenocarcinomas (CRCs), its prognostic value based on the tumor site, tumor stage, and patient ethnicity was not assessed. Therefore, in this study, we investigated whether the prognostic value of p27(kip-1) expression varies with the tumor site, tumor stage and patient ethnicity. EXPERIMENTAL DESIGN: We evaluated 206 (85 African Americans and 121 Caucasians) archival tissue specimens of first primary CRCs for immunohistochemical expression of p27(kip-1), and its prognostic significance was analyzed using univariate Kaplan-Meier and multivariate Cox regression survival methods. RESULTS: Although, similar proportion of CRCs with decreased p27(kip-1) expression was observed in all stages (range, 26-36%), the decreased p27(kip-1) expression has been shown as a marker of poor prognosis only for patients with stage III tumors both in univariate (log-rank test, P = 0.014) and multivariate (hazard ratio = 3.2, 95% confidence interval = 1.3-7.7; P = 0.01) survival analyses. The decreased expression of p27(kip-1) was associated with a high histologic grade (P = 0.016) in stage II CRCs, and with distal tumors (P = 0.001), tumor invasion (P = 0.044), and with local recurrence (P = 0.008) in stage III CRCs. CONCLUSIONS: No prognostic significance was found for p27(kip-1) expression in stages I, II, or IV CRCs, and its prognostic value was not associated with either ethnicity or tumor location. These studies suggest that decreased expression of p27(kip-1) is an indicator of poor prognosis and aids in identifying a subset of patients with aggressive forms of stage III CRCs.     

Histopathological parameters with Ki-67 and bcl-2 in the prognosis of meningiomas according to WHO 2000 classification

AIMS AND BACKGROUND: Meningiomas are classified following the WHO system of 2000 into three grades, benign (grade I), atypical (grade II), and anaplastic (grade III). We investigated the relation between tumor grade and Ki-67 and bcl-2. METHODS: In the present study, 246 cases of meningioma were reclassified according to the WHO 2000 system. The relationship between tumor grade and morphological parameters like pattern, mitotic index, cellularity, pleomorphism, nucleoli, small cell population with high nucleus/cytoplasmic ratio, necrosis and brain invasion was examined. Follow-up data were available for only 80 patients. RESULTS: A correlation was found between all morphologic parameters except for brain invasion. These parameters were related to a poor prognosis. There was no statistically significant difference in the prognosis between WHO grade I and grade II, whereas these two grades collectively exhibited significantly better survival than WHO grade III. Immunohistochemical staining for Ki-67 and bcl-2 was performed, and correlations between their expressions and other clinicopathological findings were investigated. Ki-67 and bcl-2 expression was correlated with tumor grade, and the higher the tumor grade, the higher the Ki-67 and bcl-2 expression. In conclusion, tumor grade appeared to be the most important parameter for a prognosis of meningiomas. CONCLUSIONS: Ki-67 and bcl-2 expression might participate in carcinogenesis and when used with the grading system could provide additional benefit in assessing the biological behavior of the tumor.