胃癌组织中p57kip2和Ki-67的表达及意义

目的探讨胃癌组织中p57kip2和Ki-67的表达及二者相关性。方法采用免疫组化Envision二步法检测40例胃癌组织的p57kip2和Ki-67。结果p57kip2和Ki-67在胃癌组织中的阳性表达率分别为35%（14/40）和87.5%（35/40）,均与胃癌组织的病理组织学分级、临床分期、淋巴结转移有关（P〈0.05）,而与组织学类型无关（P〉0.05）。p57kip2和Ki-67表达强度呈负相关（r=-0.326,P〈0.01）。结论胃癌组织中p57kip2表达下调,Ki-67表达上调,在胃癌的发生发展过程中发挥着重要的作用。     

Ezrin蛋白在结肠癌组织中的表达及意义

目的进一步探讨结肠癌的发生、发展机制。方法应用免疫组织化学染色法检测69份结肠癌组织及其对应癌旁良性组织、23份转移淋巴结组织中Ezrin蛋白、Ki-67蛋白表达,分析Ezrin蛋白表达与结肠癌临床病理特征及Ki-67蛋白表达的关系。结果Ezrin、Ki-67蛋白在结肠癌组织及转移淋巴结组织中的阳性表达率均明显高于癌旁组织（P均〈0．01）,Ezrin蛋白在结肠癌组织中的表达与组织分化程度及有无淋巴结转移、浆膜侵犯有关（P均〈0．01）;Ezrin蛋白与Ki-67蛋白表达呈显著正相关,P〈0．05（r=0．317）。结论Ezrin蛋白在结肠癌发生、发展中起重要作用;此为结肠癌的分子靶向治疗提供了依据。     

结肠癌组织中p53和凋亡相关基因bcl-2、bax的表达及其临床意义

组织芯片已广泛应用于恶性肿瘤的相关研究，但用于研究相关癌基因在结肠癌中表达变化的报道尚较少。目的：研究结肠癌、结肠腺瘤和癌旁结肠黏膜组织中p53和凋亡相关基因bcl-2、bax的表达及其临床意义。方法 取85例结肠癌、18例结肠腺瘤和9例癌旁结肠黏膜组织分别制成72点和104点两块组织芯片，以免疫组化方法检测芯片中p53、bel-2和bax的表达。结果：p53、bcl．2和bax在结肠癌、结肠腺瘤和癌旁结肠黏膜组织中的表达有显著差异（P〈0．01），p53、bel-2在结肠癌中的表达高于结肠腺瘤和癌旁结肠黏膜组织，bax在结肠癌中的表达低于结肠腺瘤和癌旁结肠黏膜组织。p53和bax在不同组织学分化程度结肠癌中的表达有显著差异（P〈0．01，P〈0．05），但两者之间无相关性（L=-0．081，P〉0．05），p53与bcl-2的表达呈正相关（rs=0．245，P〈0．01）。bcl-2的表达与结肠癌临床病理参数无关。结论：p53异常表达可能是结肠癌发生中的较晚期事件，bcl-2高表达和bax低表达可能参与了结肠癌的形成过程。bax低表达的结肠癌细胞更具有恶性分化潜能。     

中老年口腔癌前病变、口腔鳞癌中Ki-67蛋白异常表达的研究

目的 探讨Ki—67在口腔癌前病变、口腔鳞癌中的表达情况及其作用。方法 采用免疫组化SABC法检测10例正常口腔粘膜、8例上皮单纯增生、20例上皮异常增生和32例鳞状细胞癌组织中Ki—67的表达。结果 口腔鳞癌发展过程中存在看明显的Ki-67表达的上调；各组间Ki-67标记指数均存在差异显著性(P＜0．05)；上皮单纯增生组与轻、中度上皮异常增生组织中的Ki—67标记指数差异无显著性意义，但较重度异常增生上皮组织均有显著性差异(P＜0．05)；鳞癌各病理分级之间Ki—67标记指数差异无显著性(P＞0．05)；各类疾病中，老年组的Ki—67标记指数高于相应的中年组。结论 Ki—67的异常表达可能是口腔鳞癌发生发展过程中的早期事件，其基底上层细胞着色可视为是上皮异常增生的标志，同类疾病中，老年人的增殖活性较中年人有所增高。     

MDM2与P14ARF在结肠肿瘤中的表达及意义

目的 探讨MDM2和P14ARF（alternative reading frame)在人结肠癌组织中的表达及其意义。方法 用免疫组织化学方法检测36例癌旁正常结肠组织，28例结肠腺瘤及42例结肠癌中二者的表达及其与组织分化程度的关系。结果 MDM2、P14ARF在癌旁正常结肠组织，结肠腺瘤，结肠腺癌中的阳性表达率分别为0、0、21．4％和100％、82．14％、80．95％。MDM2在结肠腺癌中的表达率明显高于癌旁正常结肠组织及腺瘤组织（P＜0．05），P14ARF在结肠腺瘤和结肠腺癌中的表达率均明显低于癌旁正常结肠组织（P＜0．05）。MDM2和P14ARF在不同分化程度结肠癌中的表达率分别为11．1％，24．0％，25．0％和88．9％、92．0％、37．5％。MDM2在不同分化程度结肠癌中的表达无明显差异（P＞0．05），而P14ARF在低分化结肠癌中的表达明显低于高分化和中等分化的结肠癌（P＜0．05）。结论 MDM2和P14ARF在人结肠癌中的表达异常可能与结肠癌的发生发展有关。     

Brgl在结肠癌中的表达研究

Brgl是一种抑癌基因,参与染色质重塑过程,在细胞增殖、分化过程中起重要作用。研究发现Brgl参与了某些恶性肿瘤的发生。目的：检测Brgl在结肠癌中的表达,初步探讨Brgl与结肠癌的关系。方法：应用免疫组化法检测30例结肠癌、30例结肠腺瘤、20例癌旁组织中Brgl的表达情况。结果：Brgl在结肠癌组织中的表达强度显著高于结肠腺瘤和癌旁组织（P〈0．05）,结肠腺瘤与癌旁组织中的表达强度差异无统计学意义（P=0．05）。Brgl在结肠癌、结肠腺瘤、癌旁组织中的阳性表达率分别为86．7％、60．0％、25．0％,结肠癌和结肠腺瘤组织Brgl阳性表达率显著高于癌旁组织（P〈0．05）,结肠癌组织Brgl阳性表达率显著高于结肠腺瘤组织（P〈0．05）。结论：Brgl可作为判断结肠肿瘤分化程度的生物学指标。     

胰腺癌组织Survivin与Ki-67的表达及其意义

目的:探讨Survivin和Ki-67在胰腺癌组织中的表达及其与临床病理特征的关系．方法:采用免疫组织化学技术检测各期胰腺癌86例及癌旁组织78例中Survivin和Ki-67的表达水平,并结合病理特征进行分析。结果:胰腺癌旁组织或良性肿瘤旁组织不表达Survivin 蛋白．胰腺癌组织Survivin阳性表达率为87．9％,显著高于胰岛细胞癌(12．7％)或胰岛细胞瘤(5．2％)(P<0．01),而且Survivin表达程度与肿瘤分化程度、淋巴结转移相关(P<0．05)．Ki-67蛋白在胰腺癌组织中阳性表达率为 94．4％,显著高于胰岛细胞癌或胰岛细胞瘤组(P<0．01), 并与胰腺癌组织分化程度相关(P<0．05)．两种蛋白表达有高度相关性(r=0．87)．结论:Survivin和Ki-67在胰腺癌组织中过表达,并且与胰腺癌病理特征密切相关．Survivin可能是反应胰腺癌预后不良的指标．     

凋亡调控通路P53-MDM2-P14ARF对结肠癌生物学行为的影响

采用免疫组织化学 S- P法检测 3 6例正常结肠组织、 2 8例结肠腺瘤及 42例结肠癌组织中凋亡调控蛋白P53、 MDM2 、 P1 4 ARF三者的表达。P53和 MDM2 在结肠癌中的表达明显高于正常结肠组织 ( P <0 .0 5 ) ,P1 4 ARF在结肠腺瘤和结肠癌中的表达明显低于正常结肠组织 ( P<0 .0 5 )。P53和 MDM2 在结肠癌中的表达与分化程度及临床分期无明显关系 ( P >0 .0 5 ) ,而 P1 4 ARF在低分化及 C期结肠癌中的表达明显低于高分化及 A期结肠癌 (P <0 .0 5 )。三者的相关分析提示 ,P53与 MDM2 之间为正相关 ( r =0 .63 3 9) ,与 P1 4 ARF之间为负相关 ( r =-0 .9169) ,MDM2 与 P1 4 ARF之间亦存在负相关 ,但相关不显著 ( r=- 0 .3 2 68)。认为 P53、 MDM2 和 P1 4 ARF在人结肠组织中的表达异常可能与结肠癌的多种生物学行为有关 ,三者联检的协同表达可作为结肠癌辅助诊断和判断预后的参考指标     

ID-1、Ki-67及Bcl-2在食管鳞状细胞癌中的表达及意义

目的探讨食管鳞状细胞癌中DNA结合抑制蛋白-1（inhibitors of DNA binding1，ID-1）与Ki-67及Bcl-2表达的关系及其临床意义。方法应用免疫组织化学方法检测118例食管鳞状细胞癌手术切除标本及20例癌旁正常组织中ID-1、Ki-67及Bcl-2的表达情况。结果食管鳞状细胞癌中ID-1、Ki-67及Bcl-2表达上调，阳性比例分别为86．44％、81．36％和59．32％；ID-1及Bcl-2表达程度与肿瘤组织分化程度正相关（分别为r=0．289，P=0．002；及r=0．319，P=0．001）；Ki-67表达程度与肿瘤组织分化程度负相关（r=-0．320，P〈0．001）；ID-1与Bcl-2表达正相关而与Ki-67表达无关；ID-1、Ki-67及Bcl-2表达与患者的年龄、性别及是否伴淋巴结转移均无关。结论细胞凋亡抑制可能是ID-1参与食管鳞状细胞癌发生发展的主要机制，ID-1不适用于评价食管鳞状细胞癌的淋巴结转移。     

结直肠癌组织中Ki-67和pAKT的表达及其临床意义

[目的]探讨结直肠癌组织中Ki-67和pAKT的表达及其临床意义,为临床诊治结直肠癌提供依据。[方法]选取结直肠癌患者80例,患者均经病理确诊为结直肠癌。应用免疫组织化学SP法检测80例结直肠癌组织(结直肠癌组)、80例结直肠癌癌旁组织(癌旁组)、20例正常大肠组织(正常组)中Ki-67和pAKT的表达阳性率。分析结直肠癌患者癌组织中Ki-67和pAKT表达与结直肠癌转移、分期及预后的关系。采用Spearman相关分析法分析Ki-67及pAKT表达的相关性。[结果]结直肠癌组中Ki-67和pAKT的表达阳性率明显高于癌旁组和正常组的阳性率(P=0.000,0.000,0.012)(P=0.000,0.011,0.024)。有淋巴结转移的患者癌变组织中Ki-67和pAKT表达阳性率明显高于无淋巴结转移患者(P=0.013,P=0.009);Ⅰ+Ⅱ期患者癌组织中Ki-67和pAKT表达阳性率明显低于Ⅲ+Ⅳ分期(P=0.003,P=0.002);Ki-67与pAKT表达呈正相关关系(r=0.520,P=0.020);Ki-67阴性表达患者总生存率与Ki-67表达(+)、(++)及(+++)的患者总生存率比较差异有统计学意义(P=0.021,0.022,0.000);pAKT阴性表达患者总生存率与pAKT表达(+)、(++)及(+++)的患者总生存率比较差异有统计学意义(P=0.011,0.012,0.001)。[结论]Ki-67和pAKT异常表达与结直肠癌的发生发展密切相关,其表达上调参与肿瘤形成、发展、侵袭和转移,可作为判断结肠癌生物学行为的临床参考指标。     

Increased proliferation activity measured by immunoreactive Ki67 is associated with survival improvement in rectal／recto sigmoid cancer

AIM: To assess the expression of Ki67 as prognosticator in rectal/recto sigmoid cancer. METHODS: Samples from 146 patients with rectal and recto sigmoid cancer were studied for expression of Ki67 and its prognostic significance in comparison with clinico-pathological predictors of survival. Formalin-fixed, paraffin-embedded tissues from 6 (4.1%) patients with T1,26(17.8%) with T2,94(64.4%) with T3,and 20 (13.7%) with T4 tumors were studied. Ki67 expression was determined immunohistochemically.Samples were divided according to mean value into high (>40%) and low (≤40%) expression.Areas of extensive proliferation (>50%) were defined as 'hot spot' areas. RESULTS: Hot spot areas were present in samples regardless of histopathological grade. Lower TNM and Dukes stage and higher expression of Ki67 and presence of Ki67 hot spot areas in histopathological samples were associated with better survival, whereas no association was observed with histopathological grade (P=0.78). In Cox multivariate regression analysis, significant prognostic factors were Dukes stage (P<0.001), presence of lymph node metastases (P=0.015),age(P=0.035) and presence of Ki67 hot spot areas (P = 0.044). CONCLUSION: Proliferative activity as measured by Ki67 in rectal cancer is associated with survival improvement compared with patients with low Ki67. Areas of prognostically significant increased proliferation were found independently of histopathological tumor grade.     

Expression of p57(kip2) and its relationship with clinicopathology, PCNA and p53 in primary hepatocellular carcinoma

AIM: To investigate the expression of p57kip2 and its relationship with clinicopathology, PCNA and p53 in primary hepatocellular carcinoma (HCC). METHODS: Expression of p57kip2, PCNA and p53 in tumor tissues from 32 patients with HCC and 10 liver tissues of normal persons was detected with Elivision immunohistochemical technique. RESULTS: The p57kip2 protein positive-expression rate in HCC was 56.25%, lower than that in normal tissues (100%, P<0.05). The reduced expression of p57kip2 protein correlated significantly with moderate or low differentiation of tumor cells (P = 0.007 <0.05), high clinical stage (P= 0.041 <0.05) and poor prognosis (P= 0.036 <0.05), but did not correlate significantly with metastasis, tumor size, level of AFP and age (P>0.05). The PCNA positive-expression rate was 56.25%, which was correlated significantly with the expression of p57kip2 (P= 0.025<0.05). The p53 positive-expression rate was 46.88%, which was not correlated significantly with the expression of p57kip2 (P>0.05). CONCLUSION: There is a marked loss or absence of p57kip2 expression and high expression of PCNA in HCC, which are involved in carcinogenesis and development of HCC. The p57kip2 and p53 may induce apoptosis via different mechanisms.     

胰腺癌p57~(kip2)、视网膜母细胞瘤蛋白和增殖细胞核抗原的表达及与临床病理的关系

目的 探讨细胞周期蛋白依赖性激酶抑制因子p57~(kip2),视网膜母细胞瘤蛋白(Rb)和增殖细胞核抗原(PCNA)在胰腺癌发生发展中的作用。方法 应用免疫组化技术,对32例胰腺癌及癌旁组织中p57~(kip2)蛋白和PCNA表达进行检测。结果 p57~(kip2)蛋白阳性表达率在胰腺癌组织中为46.9％,显著低于癌旁胰腺组织的75.0％(x~2=5.317,P<0.05),并与胰腺癌组织分化程度有关(P<0.05),而与淋巴结转移无关(P>0.05)。Rb蛋白阳性表达率在胰腺癌组织中为50％,显著低于癌旁胰腺组织的78.1％(x~2=5.497,P<0.05)。PCNA阳性表达率在胰腺癌组织中为71.9％,显著高于癌旁胰腺组织的43.8％(x~2=5.189,P<0.05),并与胰腺癌组织分化程度和淋巴结转移均有关(P<0.05)。p57~(kip2)蛋白阳性表达组Rb蛋白阳性表达率为53.3％;p57~(kip2)蛋白阴性表达组Rb蛋白阳性表达率为47.1％,两组间无相关性(γ=0.16507,P>0.05)。结论 P57~(kip2)、Rb蛋白低表达和PCNA蛋白过度表达与胰腺癌的发生发展有关。     

Expression of cell cycle regulator p57^kip2, cyclinE protein and proliferating cell nuclear antigen in human pancreatic cancer： An immunohistochemical study

AIM: To investigate the effects of p57kip2, cyclinE protein and proliferating cell nuclear antigen (PCNA) on occurrence and progression of human pancreatic cancer. METHODS: The expression of p57kip2, cyclinE protein and PCNA in tumor tissues and adjacent tissues from 32 patients with pancreatic cancer was detected by SP immunohistochemical technique. RESULTS: The positive expression rate of p57kip2 protein in tumor tissues was 46.9%, which was lower than that in adjacent pancreatic tissues (x2 = 5.317, P<0.05). p57kip2 protein positive expression remarkably correlated with tumor cell differentiation (P<0.05), but not with lymph node metastasis (P>0.05). The positive expression rate of cyclinE protein in tumor tissues was 68.8%, which was higher than that in adjacent pancreatic tissues (x2 = 4.063, P<0.05). CyclinE protein positive expression significantly correlated with tumor cell differentiation and lymph node metastasis (P<0.05). The positive expression rate of PCNA in the tumor tissues was 71.9%, which was higher than that in adjacent pancreatic tissues (x2 = 5.189, P<0.05). PCNA positive expression remarkably correlated with tumor cell differentiation and lymph node metastasis (P<0.05). CONCLUSION: The decreased expression of p57kip2 and/or overexpression of cyclinE protein and PCNA may contribute to the occurrence and progression of pancreatic cancer. p57kip2, cyclinE protein, and PCNA play an important role in occurrence and progression of pancreatic cancer.     

环氧合酶-2、基质金属蛋白酶-9和核增殖抗原在胃癌组织中的表达及临床意义

目的 探讨环氧合酶-2(COX-2)、基质金属蛋白酶-9(MMP-9)及核增殖抗原(Ki67)在胃癌中的表达与胃癌发生、浸润和转移的关系.方法 选择2003年1月至2005年12月手术切除、病理证实的胃癌存档蜡块标本58例,其中男37例,女21例.年龄31～76岁,中位年龄58.2岁.另取上述胃癌根治术患者距肿瘤5～6 cm的癌旁组织作对照.采用免疫组化法检测胃癌组织中COX2、MMP-9、Ki67的表达.结果 COX-2、MMP-9在胃癌组织中的表达率分别为82.76%和68.9%,均高于对照组(37.93%和24.14%,P＜0.01).COX-2、MMP-9的表达与胃癌患者性别、年龄、部位及大小无相关性(P＞0.05),与胃癌浸润深度、淋巴结转移及TNM分期有关(P＜0.05),MMP-9还与胃癌分化程度相关(P＜0.05).COX-2与MMP-9在胃癌组织中的表达有相关性(P＜0.05,C=0.359).MMP-9、COX-2表达阳性者Ki67表达水平高于阴性者,两者间差异有统计学意义(P＜0.01).结论 COX-2、MMP-9、Ki67在胃癌浸润、转移过程中起重要作用,共同促进肿瘤的发生、发展.     

结肠癌中心和边缘组织增殖能力的差异及相关基因的表达

目的探索结肠癌组织不同区域肿瘤细胞是否存在增殖能力的差异，且这种区域性差异和多重抑痛基因p16及其可变读码框架pl4基因的表达情况及其甲基化状态的相关性。方法免疫组化法测定癌块不同区域增殖蛋自Ki67和P16、P14的表达差异，激光显微切割技术结合甲基化特异性PCR、巢式逆转录PCR观察同一癌块不同区域癌细胞p16及p14基因甲基化状态的改变及其mRNA的表达情况。结果在42份癌组织标本的中心，增殖蛋自Ki67均呈强阳性表达，而P16和P14蛋白表达缺失；在癌组织标本的边缘．有13份Ki67表达阳性（30．1％）。不同区域癌细胞的增殖能力差异有统计学意义（P〈0．05）．且与年龄、性别、Dukes分期、p14的表达无关，但与p16的表达显著相关（X^2=25．37，P〈0．01）。且p16基因的甲基化状态和mRNA的表达也存在明冠的区域性差异（P〈0．05）。结论人结肠癌组织中存在肿瘤细胞增殖能力的区域性差异，在癌组织边缘肿瘤细胞侵袭力增强的同时增殖能力下降，癌边缘区P16基因去甲基化后的再表达可能是这一细胞事件的分子原因。     

Expression of p57kip2, Rb protein and PCNA and their relationships with clinicopathology in human pancreatic cancer

AIM: To investigate the effects of inhibiting factor of cellcycle regulation p57kip2, retinoblastinoma protein (Rb protein)and proliferating cell nuclear antigen (PCNA) in the genesisand progression of human pancreatic cancer.METHODS: The expression of p57kip2, Rb protein and PCNAin tumor tissues and adjacent tissues of 32 patients withpancreatic cancer was detected with SP immunohistochemicaltechnique.RESULTS: p57kip2 protein positive-expression rate in tumortissues of pancreatic cancer was 46.9 %, which was lowerthan that in adjacent pancreatic tissues (75.0 %) (x2=5.317,P＜0.05), p57kip2 protein positive-expression correlatedsignificantly with tumor cell differentiation (well-differentiationversus moderate or low-differentiation, P＜0.05) but did notcorrelate significantly with lymph node metastasis (lymph nodemetastasis versus non-lymph node metastasis, P＞0.05); Rbgene protein positive-expression rate in tumor tissues was50.0 %, which was also lower than that in adjacent pancreatictissues (78.1%) (x2=5.497, P＜0.05); PCNA positive-expression rate was 71.9 %, being higher than that inadjacent pancreatic tissues (43.8 %) (x2=5.189, P＜0.05),PCNA positive-expression also correlated significantly withtumor cell differentiation and lymph node metastasis (well-differentiation versus moderate or low- differentiation, lymphnode metastasis versus non-lymph node metastasis, P＜0.05).Rb protein positive-expression rate in the tumor tissues ofp57kip2 protein positive-expression group was 53.3 %; andRb protein positive-expression rate in the tumor tissues ofp57kip2 protein negative-expression group was 47.1%. Therewas no significant relationship between the two groups(r=0.16507, P＞0.05).CONCLUSION: The decreased expression of p57kip2, Rbprotein or over-expression of PCNA protein might contributeto the genesis or progression of pancreatic cancer, p57kip2,Rb protein and PCNA may play an important role in genesisand progression of pancreatic cancer.     

SDF-1/CXCR4 signal is involved in decreased expression of p57kip2 in de novo MDS patients

p57kip2 is considered as a candidate tumor suppressor gene involvement in cell cycle control. In this study, we explored the expression of p57kip2 in various myelodysplastic syndrome (MDS) subsets by real-time quantitative PCR, as well as the relationship between p57kip2 and CXC receptor 4 (CXCR4). We also searched the role of stromal cell-derived factor-1 (SDF-1)/CXCR4 signal in p57kip2 expression in vitro. The expression of p57kip2 decreased in MDS cases (low grade MDS, P<0··001, n = 46; high grade MDS, P<0··001, n = 21), compared with that in control group. Patients with poor karyotype (according to IPSS) had lower p57kip2 than that in the normal group (P<0··05). p57kip2 expression increased after treatment with decitabine in the cases that had achieved response (P = 0··009, n = 7). Additionally, a positive correlation between p57kip2 and CXCR4 was investigated (r = 0··652, P<0··001, n = 67). p57kip2 expression in bone marrow mononuclear cells of normal controls increased significantly when co-cultured with SDF-1 in vitro, which could be blocked by AMD3100, whereas SDF-1 only induced a mild increase in p57kip2 in MDS. In conclusion, low expression of p57kip2 is common in MDS, which may play an important role in MDS pathogenesis. Reduced response to SDF-1 contributed to low expression of p57kip2 in MDS cases.     

Immunoreactivity evaluation of mutant p53 gene product with DNA ploidy pattern in colorectal carcinoma

BACKGROUND/AIMS: Studying p53 protein expression in tumor cells is one of the effective methods for detecting p53 gene mutations. This study attempted simultaneous monitoring of p53 overexpression in colon cancer using immunohistochemical and immunoblotting techniques and also to compare abnormalities of p53 with DNA ploidy and clinicopathological variables. METHODOLOGY: The occurrence of p53 protein expression was analyzed in forty-nine fresh colorectal cancer specimens by immunohistochemical and p53 protein expression also demonstrated by Western immunoblotting technique in 28 colorectal cancer specimens, using an anti-human p53 monoclonal antibody (Do-7), and 25 normal colon mucosa as a negative control. DNA ploidy in 36 specimens of colon cancer tissues was determined by Flow cytometry. RESULTS: Overexpression of p53 protein was detected immunohistochemically in 53.1% (26 of 49) of the tumor specimens. DNA ploidy was performed in 36 cases, 55.6% (20 of 36) of colon cancer specimens were DNA aneuploidy, p53 immunostaining was positive in 60% of cases with DNA aneuploidy compared to 31.3% in diploid tumors (p<0.001). There was no significant association between p53 immunostaining and clinicopathological variables. Overexpression of p53 protein was demonstrated in nuclear protein extract by immunoblotting in 75% (21 of 28) of colorectal carcinoma. Aneuploidy carcinomas were more frequently p53 positive by immunoblotting than DNA diploidy carcinomas; 76.5% (13 of 17) vs. 72.7% (8 of 11) (p<0.2). P53 expression by immunoblotting was more frequently found in good lymphocytic infiltration than moderate and poor lymphocytic infiltration (p<0.001). Also, p53 expression in right colon was significant with rectum (p<0.009). The incidence of p53 expression in Duke's stage B was significant if compared with Duke's stage C (p<0.005). Immuno-reactivity of p53 expression was detected by immunostaining and immunoblotting in 89.3% (25 of 28) of colorectal cancer. P53 immunoreactivity by immunostaining and immunoblotting were closely related to the clinicopathological variables such as pathological type (p<0.01), lymphocytic infiltration (p<0.0001), tumor grade, and tumor site (p<0.001). DNA aneuploidy was more frequently p53 positive than DNA diploid tumor by immunostaining and immunoblotting (p<0.001). CONCLUSIONS: Immunohistochemistry confirmed by immunoblotting assay is a sensitive method for detecting the trace amount of p53 protein and provides valuable information for the understanding of colorectal cancer biology.     

Cytotoxic and antiproliferative activity of the single agent epirubicin versus epirubicin plus tamoxifen as primary chemotherapy in human breast cancer: a single-institution phase III trial

This study was designed to address whether simultaneous primary chemo-hormonal therapy provides additional activity compared with chemotherapy alone in breast cancer patients with operable or locally advanced disease. Between January 1997 and January 2002, 211 consecutive patients with T2-4, N0-1, M0 breast cancer were randomized to receive either epirubicin alone (EPI) or epirubicin plus tamoxifen (EPI-TAM). Ki67 expression was evaluated immunohistochemically in tumor specimens obtained before chemotherapy by incision biopsy and at definitive surgery. Tumor shrinkage of >50% was obtained in 76% of patients randomized in the EPI arm and 81.9% of patients randomized in the EPI-TAM arm (not significant). The corresponding rates of clinical and pathological complete response were 20.2 and 21.9% (not significant), and 4.8 and 6.7% (not significant), respectively. Pathologically complete response was more frequently observed in estrogen receptor (ER)-negative (ER-) tumors (P=0.04) and correlated with elevated baseline Ki67 expression (P<0.01). Both EPI and EPI-TAM treatments resulted in a significant reduction in Ki67 expression, either in overall patients (P=0.000) or in patients with ER+ breast cancer (P=0.000). The reduction in Ki67 immunostaining in the EPI-TAM arm was greater than in the EPI arm, leading to a lower Ki67 expression at post-operative residual histology (P=0.0041). The addition of tamoxifen to epirubicin chemotherapy did not improve the response rate but led to a significantly higher reduction in the Ki67 expression. Baseline elevated Ki67 expression and the ER- status were both associated with a greater chance of obtaining a pathological complete response at residual histology.