脑胶质瘤中Jab1和p27的表达与意义

目的 探讨Jab1和p27在脑胶质瘤中的表达、意义以及相互关系.方法 运用免疫组化方法检测70例胶质瘤和8例对照脑组织标本中Jab1、p27蛋白的表达.Western blot检测6例新鲜胶质瘤标本中相应分子的表达.结果 Jab1在对照脑组织中表达不明显,在Ⅱ、Ⅲ、Ⅳ级胶质瘤中阳性率分别为21.2%、65.4%、91.7% 三者之间的表达水平差异有统计学意义(P<0.001).p27在对照脑组织中表达明显,在Ⅱ、Ⅲ、Ⅳ级胶质瘤中阳性率分别为93.8%、53.8%、25.0%,三者之间的表达差异有统计学意义(P<0.001).Western blot结果显示Jab1与p27在胶质瘤中的表达水平与肿瘤细胞的恶性程度相关.相关分析显示:胶质瘤中Jab1蛋白表达与增殖指标Ki-67表达呈正相关,与p27蛋白表达呈负相关;p27蛋白表达与Ki-67表达呈负相关(P<0.001).结论 胶质瘤中Jab1的异常高表达可能是抑制p27表达的重要因素.Jab1与p27的异常表达可能在胶质瘤的发生发展过程中起促进作用.     

磷酸化P27kip1的表达与非霍奇金淋巴瘤的恶性相关

目的探讨P27kip110位丝氨酸(Ser10)和187位苏氨酸(Thr187)磷酸化形式的蛋白质表达水平与非霍奇金淋巴瘤(NHL)恶性程度的关系。方法采用免疫组织化学方法检测88例NHL及15例良性增生淋巴结中Ser10、Thr187磷酸化P27kip1和P27kip1蛋白的表达,结合临床及病理资料进行统计分析。结果两种磷酸化位点的P27kip1蛋白在良性增生淋巴结(不包括生发中心)中的阳性率明显低于NHL,随着肿瘤侵袭性的增加,两种磷酸化位点的P27kip1蛋白表达水平增高,与增殖指标Ki-67呈正相关。Thr187磷酸化P27kip1蛋白的阳性率与P27kip蛋白表达水平呈正相关,Ser10磷酸化P27kip1蛋白的阳性率与P27kip1蛋白表达水平表现为负相关。结论磷酸化的P27kip1与NHL的恶性程度有关,联合检测磷酸化P27kip1与P27kip1蛋白的表达水平可为NHL的临床诊断和治疗提供参考。     

Cyclin D1和p16、p27在脑胶质瘤中的表达及其与PCNA的相关性

目的检测Cyclin D1和p16、p27以及PCNA在脑胶质瘤中的表达状况,以探讨不同病理类型脑胶质瘤中各自的表达及其相关性.方法应用免疫组化S-P法,检测12例正常脑组织、58例脑胶质瘤组织中Cyclin D1、p16、p27及PCNA表达及其特征.结果Cyclin D1在由低度恶性胶质瘤向高度恶性胶质瘤转化中阳性表达逐渐增强(χ2检验,P＜0.005,χ2=51.67);而p16、p27阳性表达却是随着胶质瘤恶性程度的升高而降低(χ2检验,P值均＜0.005,χ2分别为15.41和12.81).Cyclin D1与PCNA呈正相关,rs=0.745;p16和p27与PCNA呈负相关,rs分别为-0.566和-0.612.结论脑胶质瘤中Cyclin D1的表达程度对胶质瘤的细胞增殖活性起促进作用,而p16、p27的表达则起抑制作用.     

脑胶质瘤中β-catenin和细胞周期素D1表达的意义

目的:研究β-catenin与Cyclin D1蛋白在脑胶质瘤的表达及其意义.方法:应用免疫组织化学SABC法检测49例脑胶质瘤组织和5例正常脑组织中β-catenin和Cyclin D1的蛋白表达.男30例, 女19例, 年龄12～75岁, 平均42.56岁.结果:在正常脑组织和脑胶质瘤中, β-catenin蛋白阳性的比例分别为2/5和38/49(P<0.01), Cyclin D1蛋白阳性的比例分别为1/5和42/49(P<0.01);比较β-catenin和Cyclin D1在脑组织、低级别脑胶质瘤和高级别脑胶质瘤中的光密度值, 发现发现各组之间均存在着统计学差异(P<0.05或P<0.01);β-catenin的过度表达与Cyclin D1的过度表达显著相关(r=0.6395, P<0 05).结论:脑胶质瘤细胞β-catenin与Cyclin D1表达增强, 可能参与胶质瘤的发生.     

甲状腺乳头状癌中MCM7、CDK2、p27蛋白的表达及意义

目的 探讨MCM7、CDK2及p27蛋白与人甲状腺乳头状癌(papillary thyroid carcinoma,PTC)发生、发展的关系.方法 采用免疫组织化学SP法检测40例PTC、30例甲状腺腺瘤、30例结节性甲状腺肿及20例正常甲状腺组织中MCM7、CDK2、p27蛋白的表达.结果 PTC中MCM7、CDK2蛋白的阳性表达率分别为100.00%(40/40)、80.00%(32/40),两者均明显高于甲状腺腺瘤、结节性甲状腺肿及正常甲状腺组织(P<0.01,P<0.01).PTC中p27蛋白的阳性表达率为22.50%(9/40),明显低于甲状腺腺瘤、结节性甲状腺肿及正常甲状腺组织(P<0.01).PTC中MCM7与CDK2蛋白的表达呈正相关(r=0.550,P<0.01),MCM7、CDK2及p27蛋白的表达呈负相关(r=-0.334,P<0.05;r=-0.413,P<0.01).结论 MCM7、CDK2蛋白的高表达及p27蛋白的低表达变化与PTC可能存在关联,三者联合检测或许可以作为临床早期诊断和评价甲状腺肿瘤细胞增殖活性的潜在的参考指标.     

人脑星形细胞肿瘤IL-8的表达及其与血管生成的关系

目的：探讨IL-8,VEGF在脑胶质瘤中的表达及与血管生成的关系。方法：应用由45例人脑星形细胞肿瘤和6例正常脑组织组成的组织芯片，采用免疫组织化学技术分别进行IL-8，VEGF，CD34标记并进行半定量，观测在不同病理分级胶质瘤中的表达及与微血管密度（MVD）之间的关系。结果：6例正常脑组织中不表达IL-8，VEGF。45例脑胶质瘤中，27例IL-8呈阳性表达，32例VEGF呈阳性表达，Ⅲ，Ⅳ级脑胶质瘤中IL-8，VEGF的表达比Ⅰ级、Ⅱ级明显增强，IL-8，VEGF评分为强阳性的胶质瘤内MVD明显高于评分为阴性和阳性的MVD（P<0.01）。IL-8表达与MVD呈正相关（rs=0.64，P<0.01）。VEGF表达与MVD之间呈正相关（rs=0.44，P<0.01）。IL-8表达与VEGF表达之间亦呈正相关（rs=0.56，P<0.01）。结论：IL-8，VEGF的表达与胶质瘤病理分级、MVD密切相关，二者在胶质瘤的血管生成中可能相互关联、共同调节肿瘤血管生成。     

胃癌NET-1、Ki-67表达及意义

目的 研究胃癌组织中NET-1和Ki-67表达与其预后的关系.方法 分别应用免疫组化EnVision两步法检测86例胃癌组织中NET-1和Ki-67的表达,对两指标均阳性病例行免疫组化双标双染方法,原位检测两指标的表达特点和比邻关系.所有病例随访60月以上.结果 胃癌组织中 NET-1和Ki-67高表达分别为56.98%和74.42%,两指标阳性表达呈正相关(P<0.01).两指标高表达分别与癌分化呈负相关(均P<0.01);与癌临床分期呈正相关(均P<0.05);与患者生存率呈负相关(均P<0.05),其3年、5年生存率均低于相应的低表达组或阴性组(P<0.05,P<0.01);NET-1表达还与癌淋巴结转移呈正相关(P<0.01).结论NET-1、Ki-67基因蛋白高表达反映胃癌细胞群体增殖活性,上调癌进展,预后较差.     

肝细胞癌中磷酸化p27kip1与JAB1的表达及意义

p27^kip1（p27）是重要的细胞周期负性调控因子,其蛋白表达水平和亚细胞分布改变与肝细胞癌的发生密切相关 。在肿瘤细胞中存在多种转录后途径抑制p27蛋白的表达,磷酸化是最重要的途径之一 。p27主要在细胞核内发挥作用,因此p27的胞质胞核定位与其功能活性密切相关。有证据显示在p27出核降解前必须经历10号位丝氨酸（Ser10）的磷酸化;而JAB1（c-Jun activation domain binding protein1）是与p27出核转运有关的一个接头蛋白。因此,本研究中我们检测了Ser10磷酸化p27、JAB1及p27在肝细胞癌及癌旁中的表达情况并结合临床资料探讨其中的临床病理意义。     

mTOR_P70S6K信号通路在小儿脑胶质瘤中的表达及其临床意义

目的:探讨mTOR_P70S6K信号通路在小儿脑胶质瘤组织中的表达及其临床意义。方法:随机选取脑胶质瘤患儿88例,采用SP免疫组化方法,检测脑胶质瘤组织和正常脑组织中mTOR蛋白及P70S6K蛋白的表达。并分析其与脑胶质瘤组织临床分级之间的关系。结果:mTOR蛋白及P70S6K蛋白在脑胶质瘤组织中的阳性表达率分别为81.58%(31/38)和78.95%(30/38),明显高于其在正常脑组织中的阳性表达率[分别为15%(3/20)和10%(2/20)](P<0.01)。mTOR蛋白和P70S6K蛋白在脑胶质瘤组织中的表达呈正相关(r=0.68,P<0.05),且两者在正常脑组织中的表达亦正相关性(r=0.89,P<0.01)mTOR蛋白及P70S6K蛋白阳性表达率在脑胶质瘤高级别组(Ⅲ~Ⅳ级)中的表达均明显高于低级别组(Ⅰ~Ⅱ级),说明随着肿瘤级别的升高二者的表达也增强。结论:mTOR_P70S6K信号通路在小儿脑胶质瘤中发生了特异性的激活。该通路可能与小儿脑胶质瘤的发生、发展密切相关。     

浸润性乳腺癌中Hepsin和c-Met的表达及临床病理意义

目的 探讨浸润性乳腺癌组织中Hepsin和c-Met的表达及临床病理意义.方法 采用免疫组化PV-6000方法检测106例浸润性乳腺癌中Hepsin和c-Met的表达.结果 106例浸润性乳腺癌组织中,Hepsin的阳性表达率为66.0%,c-Met的阳性表达率为58.5%,Hepsin与c-Met的表达呈正相关(rs=0.192,P<0.05);Hepsin和c-Met的表达与浸润性乳腺癌的病理分级呈正相关(rs=0.31,P<0.01;rs=0.245,P<0.01),与淋巴结转移亦呈正相关(rs=0.29,P<0.01;rs=0.26,P<0.01).结论 Hepsin和c-Met与提示浸润性乳腺癌的不良预后因素有关,可作为预测浸润性乳腺癌预后的参考指标之一.     

Cell cycle regulators in bladder cancer: a multivariate survival study with emphasis on p27Kip1

Cyclin-dependent kinase inhibitors (CKIs) prevent cyclin-dependent kinases from phosphorylating critical substrates such as retinoblastoma gene protein (pRb), hence blocking the cascade of events leading to cell proliferation. Currently, the list of CKIs includes p21WAF1/Cip1, p27Kip1, p57Kip2 (the Cip/Kip family), p15/ INK4b, p16/INK4a, p18/INK4c, and p19/INK4d (the INK4 family). Among them, p27 plays a crucial role linking extracellular growth-regulatory signals to progression to or exit from the cell cycle. Unlike p53, p16, and Rb, mutations in Kip1 and WAF1 genes are distinctly rare in bladder cancer. We analyzed immunohistochemically the expression of p27 and other interacting G1 proteins (ie, p21, p16, pRb, p53) in 120 consecutive cases of transitional cell carcinomas (TCCs) and related it to proliferation rate, clinicopathologic parameters, and survival. p27 levels were significantly higher in low-grade (P = .001), superficial (Ta-T1) (P = .001), papillary (P < .001), and slowly proliferating TCCs (rs = -0.235, P = .05). p27 also positively correlated with p16 expression (rs = 0.212, P = .05). In univariate analysis, decreased p27 expression was associated with poor overall (P = .0109) and postrelapse (P = .0344) survival, especially if combined to increased Ki-67 expression (P = .0004 and P = .036, respectively). Furthermore, in multivariate analysis, Ki-67/p27 status had the strongest bearing on the overall survival of muscle-invasive TCCs (P = .0019). Our results indicate that low p27 expression is more common in poorly differentiated muscle-invasive TCCs and is a major player in cell cycle control in these neoplasms. More importantly, the combined Ki-67/p27 expression provides prognostic information beyond that provided by conventional parameters or other cell cycle-related proteins, concerning overall survival in muscle-invasive TCCs.     

HER2状态与脑膜瘤分级及复发的相关性

目的 探讨HER2、细胞增殖指标Ki-67、胸苷激酶1(TK1)与脑膜瘤分级和良性脑膜瘤复发的相关性.方法 按2007年WHO神经系统肿瘤分类分级标准选取良性未复发的脑膜瘤、不典型脑膜瘤及恶性脑膜瘤石蜡标本各20例,并选取间期良性复发的脑膜瘤石蜡标本20例,将实验对象分为4组:良性非复发组、良性复发组、不典型组及恶性组.采用免疫组织化学MaxVision法对4组石蜡切片进行HER2、Ki-67、TK1蛋白的检测;并运用双色荧光原位杂交(FISH)法检测HER2蛋白表达阳性样本的HER2基因扩增情况.结果 免疫组织化学:(1)良性非复发组、良性复发组、不典型组和恶性组脑膜瘤的HER2阳性的例数分别为3例(15%)、6例(30%)、7例(35%)和10例(50%),随恶性程度增加,HER2蛋白阳性率升高(P<0.05);良性复发组HER2阳性率高于良性非复发组(P<0.05);(2)良性非复发组Ki-67和TK1的标记指数(U)均分别低于不典型组和恶性组(P<0.05);不典型组低于恶性组(P<0.05),随着恶性程度增高,Ki-67、TK1 LI升高;且良性复发组高于良性非复发组(P<0.05);(3)HER2与Ki-67、TK1均呈正相关(均P<0.01),Ki-67与TK1呈正相关(P<0.05).FISH法:(1)在26例HER2蛋白阳性表达的脑膜瘤组织中HER2/neu基因的扩增率为26.9%(7/26);HER2蛋白表达3+、2+者HER2/neu基因扩增比例分别为3,/4和4/6,均多于1+者(均P<0.01),3+者与2+者比较差异无统计学意义(P>0.05).(2)26例HER2蛋白阳性表达的脑膜瘤组织中9例存在17号染色体的非整倍性(34.6%),但HER2蛋白表达1+、2+、3+者间17号染色体的非整倍性出现率差异均无统计学意义(均P>0.05).结论 HER2阳性且Ki-67或TK1 LI高提示脑膜瘤恶性程度较高或复发可能性较大.脑膜瘤组织中存在HER2/neu基因的扩增.HER2、Ki-67和TK1蛋白可能可以作为临床判断脑膜瘤生物学行为的参考指标.     

胃癌组织中c-FLIP及Ki-67表达的研究

目的 研究胃癌组织中c-FLIP及Ki-67的表达情况,并依此探讨胃癌细胞的凋亡与增殖之间的关系.方法 应用免疫组织化学的方法研究c-FLIP及Ki-67在100例胃癌标本中及100例胃良性疾病标本中的表达情况.结果 在胃癌组织中c-FLIP(χ2=35.17,P<0.01)及KI有较高表达(u=13.52,P<0.01);不同分化程度的胃癌标本中,c-FLIP表达差别有统计学意义(χ2=14.83,P<0.01),而KI差别无统计学意义(u=1.00,P>0.05).结论 在胃癌的发生与发展中,细胞凋亡受抑制与细胞增殖过度之间存在相互协同作用.     

Reduced expression of p27/Kip1 is associated with the development of pulmonary adenocarcinoma

p27/Kip1 (p27), a negative regulator of cell proliferation, is a powerful prognostic marker in non-small cell lung carcinoma. To clarify the significance of p27 aberrations in the tumourigenesis of lung adenocarcinoma, p27 expression was investigated by immunohistochemistry in lung adenocarcinoma and its precursor lesion, atypical adenomatous hyperplasia (AAH), and correlated with the expression of Ki-67, cyclin D1, and cyclin E. The p27 labelling index decreased in parallel with tumour progression (24.0% to 4.5%) and was found to be lower in neoplastic lesions than in normal bronchiolar epithelial cells (48.8%). There was a negative correlation between p27 and Ki-67 expression (rho=-0.384, p<0.001). Cyclin E-positive lesions (with labelling index >/=5%) were found only in overt adenocarcinomas. The Ki-67 labelling index of cyclin E-positive, high (>/=10%) p27 expressers was lower than that of cyclin E-positive, low (<10%) p27 expressers (16.8% vs. 42.6%; p=0. 046) and was similar to that of cyclin E-negative adenocarcinomas (15.0%). These results indicate that reduced p27 expression is associated with and may play a role in progression during the development of pulmonary adenocarcinoma.     

Prognostic significance of p27 and Ki-67 expression in mucoepidermoid carcinoma of the intraoral minor salivary gland.

p27 and Ki-67, a universal cyclin-dependent kinase inhibitor and a proliferative cell marker, respectively, have been useful in predicting clinical aggressiveness in various human tumors. We studied clinicopathologic significance of these molecules in mucoepidermoid carcinoma of the intraoral minor salivary gland. Expression of p27 and Ki-67 was assessed immunohistochemically in primary mucoepidermoid carcinomas from 31 patients without distant metastasis at surgery. Correlation each of p27 and Ki-67 expression was analyzed with various clinicopathologic parameters including age, sex, primary tumor site, tumor size, nodal metastasis, clinical stage, and histologic grade. The latter was evaluated using a point-scoring scheme of Auclair et al. that consists of five histologic factors (intracystic component, neural invasion, necrosis, mitosis, and anaplasia). p27 expression was correlated inversely with histologic grade (P =.007), but with none of other factors. When the correlation of p27 expression was further examined with each of the histologic factors, it was correlated significantly with intracystic component, but not with neural invasion, necrosis, mitosis, or anaplasia. Ki-67 expression was correlated significantly with histologic grade only in the clinicopathologic factors (P <.0001), and in the histologic factors, with necrosis, mitosis, and anaplasia. Multivariate prognostic analyses were performed to identify independent risk factors for both disease-free and overall survivals. Large tumor size (P =.031, relative risk = 5.5) and low p27 expression (P =.012, relative risk = 5.2) were risk factors for worse disease-free survival. Low p27 expression (P =.015, relative risk = 15.2) was selected as a risk factor for worse overall survival. Other factors including age, sex, tumor site, nodal status, clinical stage, histologic grade, and Ki-67 did not emerge as independent risk factors in either prognostic analysis. These data suggest that p27 may be useful in estimating prognosis of the patients who have mucoepidermoid carcinoma of the intraoral minor salivary gland.     

Expression of p27(kip) and other cell cycle regulators in malignant peripheral nerve sheath tumors and neurofibromas: the emerging role of p27(kip) in malignant transformation of neurofibromas

There is little information regarding the status of cell cycle regulators in malignant peripheral nerve sheath tumors (MPNSTs) and neurofibromas (NFs). In this study, we investigated patterns of expression of p53 and pRB, cyclin-dependent kinase inhibitors (CKIs) p21 and p27, as well as cyclins D1 and E, in a cohort of 35 well-characterized MPNSTs and 16 NFs. These phenotypes were correlated with proliferative index, as assessed by Ki-67, as well as clinicopathological parameters of poor outcome. p53 nuclear overexpression was found in 10 of 35 (29%) MPNSTs, and it was lacking in NFs (P = 0.02). There were no differences in the patterns of expression of pRB, cyclin D1, and p21 between MPNSTs and NFs. However, p27 nuclear expression was present in most NFs, but it was absent in the majority of MPNSTs, which displayed cytoplasmic staining (P < 0.001). Nuclear cyclin E expression was more pronounced in MPNSTs than in NFs. We observed inverse patterns of expression for nuclear p27 and nuclear cyclin E expression. The staining profiles of cytoplasmic p27 and nuclear cyclin E expression were found to be statistically associated (P = 0.01). High Ki-67 expression was found in 20 of 34 (59%) MPNSTs but was absent in NFs (P < 0.001). Furthermore, detection of cytoplasmic p27 expression was found to be a prognostic factor for poor survival in MPNSTs (P = 0.03, relative risk = 2.4).     

Atypical immature cervical metaplasia: immunoprofiling and longitudinal outcome

Atypical proliferations of immature cervical squamous metaplasia were reviewed and correlated with p16 and Ki-67 expression to determine whether immunoprofiling could enable more conventional classification. The longitudinal outcome of atypical immature metaplasia (AIM) and predictive role of biomarker expression were also investigated. All atypias of immature squamous metaplasia in the year 2000 were reviewed and stained with p16 and Ki-67. Biomarker features were evaluated and the Ki-67 index calculated. Diagnoses were correlated with the immunoprofile of each antibody, both separately and combined. The progression to squamous intraepithelial lesion (SIL) of lesions reclassified as AIM was determined, and biomarker immunoprofiles were correlated with outcome. The 172 atypias were reviewed as 3 (1.7%) negative, 54 (31.4%) benign, 60 (34.9%) AIM, 43 (25%) low-grade SIL (LSIL), and 12 (6.9%) high-grade SIL (HSIL). HSIL correlated significantly with a combined high index (>15%) and p16 diffusely positive profile (P = .01). Benign diagnoses correlated significantly with a low index (1%-15%) and p16 negative or focal profile (P = .01). AIM and LSIL correlations were not significant, but their profiles were very variable and nearly identical. AIM was the only pathology in 43 cases, and follow-up was available for 32 (74.4%). SIL developed in 66% (50% LSIL and 16% HSIL) and p16 positivity correlated (P = .02). p16 and Ki-67 immunoprofiling are reliable in reclassifying some atypical proliferations of immature squamous metaplasia as HSIL and some as benign. The similarity between AIM and LSIL in regard to their immunoprofile as well as outcome suggests AIM is a morphological type of LSIL.     

Immunohistochemical markers of cell cycle control applied to ovarian and primary peritoneal surface epithelial neoplasms: p21(WAF1/CIP1) predicts survival and good response to platinin-based chemotherapy.

Immunohistochemistry for p53, p21(WAF1/CIP1), and Ki-67 provides insight into the molecular events controlling the cell cycle. We tested the hypothesis that these cell cycle markers will aid in the clinical evaluation of ovarian and primary peritoneal surface epithelial neoplasms (SENs). Paraffin sections from a retrospective surgical series of 117 SENs were immunostained with anti-p53 (clone DO7, Novacastra Laboratories, UK), anti-p21(WAF1/CIP1) (clone EA10, Oncogene Science, Cambridge, MA), and anti-Ki-67 (clone MIB-1, Immunotech, Westbrook, ME). The Ki-67 proliferation index (Ki-67PI) and immunoreactivity were evaluated. One hundred seventeen SENs reacted as follows: p53 50%+ and p21(WAF1/CIP1) 65%+. Ki-67PI ranged from 4% to 88% (mean/median = 44/46%). p53 reactivity associated with transitional cell histology, decreased p21(WAF1/CIP1) staining, increased Ki-67PI, architectural/nuclear grade, and stage (P < .05, 1 x 10(-7), .01, .05/.0001, .001,). p21(WAF1/CIP1) staining was associated with endometrioid/clear cell histology, decreased Ki-67PI, architectural/nuclear grade, and stage (P < 05/.05, .05, .01/1 x 10(-8), 1 x 10(-5)). Ki-67PI associated with increased architectural/nuclear grade but not mucinous histology (P < 1 x 10(-5)/1 x 10(-6), .01). Sixty-seven patients had disease at last follow-up; 53 were dead of disease at 0 to 67 months (mean/median, 21/18), and 14 were alive with disease at 12 to 224 months (mean/median, 56/40). Fifty patients were disease free at 5 to 214 months (mean/median, 59/41). Predictors of survival include decreased Ki-67PI, stage, architectural/nuclear grade (P < 1 x 10(-6), 1 x 10(-10), 1 x 10(-10)/.005) and p21(WAF1/CIP1) IMS (multivariate P < 1 x 10(-6)). p21(WAF1/CIP1), a potent inhibitor of cyclin-dependent kinases necessary for cell cycle progression, functions as a key checkpoint in cell cycle control. Immunoreactivity for p21(WAF1/CIP1) provides prognostic information independent of other histological and clinical predictors, p53 IMS, and Ki-67PI in this series of 117 PTs with SENs. Our preliminary data suggest an interrelationship between p21(WAF1/CIP1) expression and an effective clinical response to platinin-based chemotherapy, both associated with apoptosis. Further investigation seems warranted.     

Correlation of enhanced cell turnover with prognosis of gastrointestinal stromal tumors of the stomach: relevance of cellularity and p27kip1

The aim of the present study was to determine whether expression of molecules associated with cell cycle regulation and apoptosis might reflect tumor grade and patients' prognosis of gastrointestinal stromal tumor (GIST). Forty-nine cases of gastric GIST were divided into three grades; low, intermediate, and high risk. Ki-67, cyclin A, cyclin D1, cyclin E, p16(Ink4), p21(Waf1), p27(Kip1), cyclin-dependent kinase (cdk)2, cdk4 and single-strand DNA (ssDNA) were immunohistochemically stained and assessed. Ki-67, ssDNA, cyclin A and cdk2 had higher labeling indices (LI) in high-risk than in low-risk cases. Cyclin E expression was greater in the intermediate- than in the low-risk grade. On Kaplan-Meier analysis, tumor size, necrosis, cellularity, Ki-67, ssDNA, and cyclin A LI were significantly correlated with disease-free survival. Necrosis, cellularity, and Ki-67 LI were significant as prognostic factors on univariate, and Ki-67 LI on multivariate Cox hazard tests. Within the high-risk grade, high cellularity and low p27(Kip1) subgroups had the worst prognosis. The histological grade is related to cell turnover, assessed in terms of Ki-67, ssDNA, cyclin A, cyclin E, and cdk2 levels. Ki-67, ssDNA, and cyclin A are useful for prediction of prognosis, with cellularity and p27(Kip1) expression as further prognostic factors in high-risk cases.