Expression of maspin in colon cancers: its relationship with p53 expression and microvessel density

We studied the expression of maspin in colonic adenocarcinoma compared with adenoma and metastatic adenocarcinoma as well as the relationship with its possible regulator, p53. The colonic specimens consisted of 24 adenomas, 49 adenocarcinomas, and 17 metastatic adenocarcinomas. Immunohistochemical staining of paraffin sections was done with microwave-based antigen retrieval methods. The Ki-67 index and the microvessel density were counted using an image analysis system. Maspin expression was positive in 75.5% of adenocarcinomas and 91.7% of adenomas. Only 47.1% of the nodal metastasis showed positive maspin expression. In colonic adenocarcinomas, p53 expression was positive in 44.7% of the maspin-positive groups compared with 100% of the maspin-negative groups (P < 0.005). Colonic adenocarcinomas with the positive maspin expression groups showed less intense microvessel density (181.1 ± 54.2) than those of the negative maspin expression groups (256.1 ± 75.4, P < 0.001). In conclusion, we demonstrated maspin expression in colon cancer with a sequential decreased expression rate from adenoma to metastatic carcinomas, which signifies the tumor suppressive function of maspin, and an inverse correlation with p53 and microvesel density, which indicates the regulatory effect of p53 on maspin and anti-angiogenesis effect of maspin.     

结肠肿瘤PTHrP的表达及其与P53蛋白表达关系的研究

目的 研究ＰＴＨｒＰ在肿瘤发生过程中的作用以及ＰＴＨｒＰ和Ｐ５３在结肠腺中表达的关系。方法 用免疫组织化学ＡＢＣ法对６８例结肠组织（３０例结肠腺癌,２０例腺瘤性息肉,１８例正常结肠组织）进行ＰＴＨｒＰ检测,并对其中３０例结肠腺癌进行Ｐ５３检测。结果 结肠癌组ＰＴＨｒＰ的阳性率明显高于腺瘤组（Ｐ〈０．０５）和正常组（Ｐ〈０．０５）。绫 ＰＴＨｒＰ的过度表达与细胞的恶性 经有关,与肿瘤分化程度无明显关     

p53 gene mutation and p53 protein overexpression in a patient with simultaneous double cancer of the gallbladder and bile duct associated with pancreaticobiliary maljunction

Pancreaticobiliary maljunction (PBM) is associated with the occurrence of biliary cancer due to pancreatobiliary reflux. We present a case of simultaneous double cancer of the gallbladder and bile duct. A 77-year-old woman who had jaundice, intra- and extra-hepatic biliary ductal dilatation and a space-occupying lesion in the gallbladder and lower bile duct underwent pancreatoduodenectomy. The gallbladder cancer showed papillary carcinoma without mutation of the K-ras gene and with p53 non-sense mutation of CCA (Pro) to CA (Stop) on codon 301 in exon 8. The bile duct cancer revealed a well-differentiated adenocarcinoma without mutation of the K-ras gene and with p53 miss-sense mutation of GTG (Val) to GAG (Glu) on codon 272 in exon 8. There were no mutations of either the K-ras or p53 gene in non-cancerous epithelia. In contrast, only the mucosa of the common channel had p53 protein accumulation and high cell proliferation activity. Therefore, the genetic pathway might be the same in both the gallbladder and bile duct cancer, and a high potential for carcinogenesis might be present in the epithelium of the common channel in patients with PBM.     

Expression of p53, p16 and COX-2 in pancreatic cancer with tissue microarray

BACKGROUND: Pancreatic cancer development and progression is driven by the accumulation of genetic changes. In this study we constructed tissue microarray containing specimens from pancreatic cancer, adjacent non-cancer tissue and normal tissue to survey the expression of p53, p16 and cyclooxyganase-2 (COX-2). METHODS: Tissue microarray containing 337 specimens from different stages of pancreatic cancer, adjacent noncancer tissue and normal tissues was constructed, and the expression of p53, p16 and COX-2 was assayed by immunohistochemistry to consecutive formalin-fixed tissue microarray sections. RESULTS: The expression of p53, p16 and COX-2 was significantly higher in tumorous tissues than in non-tumorons ones. A significant relationship was observed between p53 and COX-2, or p16 and COX-2. But no obvious correlation was seen between p53 and p16 expressions. Logistic regression analysis showed p53 and COX-2 as dependent predictors in pancreatic carcinogenesis, and a reciprocal relationship to neoplastic progression between p53 and COX-2. CONCLUSION: Combination analysis of p53 and COX-2 may be useful in predicting pancreatic carcinogenesis.     

p53 protein accumulation as a prognostic marker in sporadic colorectal cancer

Background and aims p53 protein plays a crucial role in the pathogenesis of a large number of malignancies. In this study, our goal was to elucidate the prognostic role of p53 overexpression and its relationship to clinicopathological variables in colorectal cancer. Materials and methods Between 1999 and 2004, surgical specimens of 258 patients who received surgical treatment for colorectal cancer at the Veterans General Hospital, Taipei were collected. p53 expression in tumor tissue was evaluated by immunohistochemical analysis using the human p53-specific mouse monoclonal antibody, PAb 1801. Results Of the 258 patients, 97 (37.6%) had overexpression of p53 in tumor tissues. The accumulation of p53 protein in tumor tissues did not correlate with age, gender, preoperative serum carcinoembryonic antigen (CEA) level, mucin content, nodal status, and tumor stage. A statistically significant correlation was found between p53 overexpression and location of the tumor in the rectum (p=0.038). Well to moderately differentiated tumors had significantly higher frequency of p53 overexpression than poorly differentiated tumors (40.0 vs 20.0%, p=0.050). Each patient was followed up for a minimum of 2 years (median 35 months). In univariate analysis, 3-year cancer-specific survival rate was significantly higher in patients with tumor p53 overexpression (88.2%) than in patients without overexpression (log rank test, p=0.037). However, in multivariate analysis, the tumour node metastasis stage remained the most significant independent prognostic factor. Conclusion The accumulation of p53 protein might have a favorable prognostic value in colorectal cancer, but it is not an independent prognostic factor.     

Expression of p53, p16 and cyclooxygenase-2 in esophageal cancer with tissue microarray

OBJECTIVE: The aim of this study was to obtain a comprehensive survey on the expression of p53, p16 and cyclooxygenase‐2 (COX‐2) in esophageal cancer progression and their clinical significance. METHODS: A tissue microarray containing 86 specimens from esophageal cancer and 40 specimens from adjacent non‐cancer tissue was constructed to survey the expression of p53, p16 and COX‐2 by immunohistochemistry. The influence of each biomarker on the histotype of esophageal lesion was assessed by logistic regression analysis. RESULTS: The expression of p53 and COX‐2 was significantly higher in tumorous tissue than in non‐tumorous tissue. As to p16, no significant difference was detected between tumorous and non‐tumorous tissue. A significant correlation was observed among p53, COX‐2 and p16 expression. Logistic regression analysis revealed that the risk factors of a tumorous histotype were the positive expression of p53 (odds ratio [OR] = 18.214) or COX‐2 (OR = 42.703), and no reciprocal relationship to neoplastic progression was recognized with p53, p16 and COX‐2. CONCLUSIONS: p53 and COX‐2 were independent predictors in esophageal carcinogenesis. Esophageal tissue with a positive expression of p53 or COX‐2 was more likely to develop esophageal cancer.     

PUMA蛋白在结肠癌组织中的表达及其临床意义

目的检测PUMA蛋白在结肠癌组织和癌旁正常组织中的表达水平,从而探讨其在结肠癌发生、发展中的作用及其临床意义。方法针对40例结肠癌组织标本及30例癌旁正常组织标本,通过免疫组化方法对其PUMA蛋白的表达进行测定。结果 PUMA蛋白在结肠癌组织中的表达阳性率为22.5%（9/40）,在癌旁正常结肠组织中表达阳性率为66.7%（20/30）,PUMA蛋白的表达与结肠癌临床病理分期、肿瘤病理分化程度、是否伴有淋巴结转移有关。结论 PUMA蛋白在结肠癌的发生、发展中起重要作用,可能成为结肠癌的分子标记物或结肠癌治疗的新分子靶点。     

Apoptosis of colon cancer: Comparison with Ki-67 proliferative activity and expression of p53

The role of apoptosis in colon cancer was investigated in terms of control of growth and expression of p53, using the nick-ended-DNA labelling method and immunohistochemistry. The apoptotic labeling index was highest in the T1 stage (24 cases), as was the proliferative activity, assessed in terms of the Ki-67 labeling index. Both labeling indices demonstrated similar overall incidence curves for the total 95 colon cancer cases, and examination of individual cases revealed a statistically significant correlation (P=0.01). However, neither index had any relation to p53. The results thus suggest that apoptosis in colon cancers has a linkage with proliferative activity that can be assessed by Ki-67 labeling, but is not regulated by the p53 system. This might contribute to the diversity of colon cancer growth.     

Down-expression of tumor protein p53-induced nuclear protein 1 in human gastric cancer

AIM: Overexpression of tumor protein p53-induced nuclear protein 1 (TP53INP1) induces G1 cell cycle arrest and increases p53-mediated apoptosis. To clarify the clinical importance of TP53INP1, we analyzed TP53INP1 and p53 expression in gastric cancer. METHODS: TP53INP1 and p53 expression were examined using immunohistochemistry in 142 cases of gastric cancer. The apoptosis of gastric cancer cells was analyzed using the TUNEL method. The relationship between the expression of TP53INP1 and clinicopathological factors was statistically analyzed. RESULTS: TP53INP1 was expressed in 98% (139/142 cases) of non-cancerous gastric tissues and was down-expressed in 64% (91/142 cases) of gastric cancer lesions from the same patients. TP53INP1 expression was significantly decreased (43.9%) in poorly differentiated adenocarcinoma compared with well or moderately differentiated adenocarcinoma (81.6%). Cancers invading the submucosa or deeper showed lower positively (59.1%) compared with mucosal cancers (85.2%). Decrease or loss of TP53INP1 expression was significantly correlated with lymphatic invasion (54.3% vs 82.0% without lymphatic invasion) and node-positive patients (31.3% vs 68.3% in node-negative patients). P53 was expressed in 68 (47.9%) patients of gastric cancer, whereas it was absent in normal gastric tissues. A significant association was also observed between TP53INP1 status and the level of apoptosis in tumor cells: the apoptotic index in TP53INP1-positive tissues was significantly higher than that in TP53INP1-negative portions. Finally, when survival data were analyzed, loss of TP53INP1 expression had a significant effect in predicting a poor prognosis (P=0.0006). CONCLUSION: TP53INP1-positive rate decreases with the progression of gastric cancer. TP53INP1 protein negativity is significantly associated with aggressive pathological phenotypes of gastric cancer. TP53INP1 is related to the apoptosis of gastric cancer cells. The decreased expression of the TP53INP1 protein may reflect the malignant grade of gastric cancer and is regarded as an adverse prognostic factor.     

结肠癌合并血吸虫感染患者癌细胞p53基因的表达

目的 研究原发性结肠癌细胞p53基因mRNA的表达水平及合并血吸虫感染后的差异,探讨其与患者临床病理特征的关系。 方法 38例原发性结肠癌患者分为两组,A组（合并血吸虫感染）20例和B组（未合并血吸虫感染）18例。应用实时荧光定量 PCR和相对定量分析法检测患者肿瘤组织中的p53 mRNA。 结果 p53 mRNA在两组中均可检出,A组中的基因表达水平显著高于B组（P＜0.05）。p53基因mRNA表达水平与年龄、性别相关无显著性,与肿瘤大小、有无淋巴结转移相关具有显著性。结论 p53基因mRNA的高水平表达与结肠癌的侵袭和发展具有显著性差异,血吸虫感染可能对结肠癌患者p53基因的突变有一定影响。     

p53 allele deletion and protein accumulation occurs in the absence of p53 gene mutation in T-prolymphocytic leukaemia and Sezary syndrome

In a series of 24 patients with chronic T-lymphoid disorders [13 T-prolymphocytic leukaemia (T-PLL) and 11 Sezary syndrome] we have studied (i) chromosome 17p abnormalities and p53 allele deletion by fluorescence in situ hybridization; (ii) mutation in the exons of the p53 gene by direct DNA sequencing; and (iii) p53 protein expression by immunocytochemistry and, in some cases, also by flow cytometry with DO-1, a monoclonal antibody to the p53 protein. The study revealed p53 deletion and accumulation of p53 protein in the absence of mutation in the exons that included the hot-spots and differs from that described in B-prolymphocytic leukaemia. Seven T-PLL and five Sezary syndrome patients had p53 overexpression, and five T-PLL and nine Sezary syndrome patients showed p53 deletion. Although the majority of cases with p53 accumulation had p53 deletion, the proportion of cells with the deletion did not correlate with the proportion of cells positive for p53 expression. Two cases of T-PLL showed strong p53 expression in the absence of p53 deletion, and one case of Sezary syndrome with p53 deletion in 97% of cells did not express p53. These findings suggest that a non-mutational mechanism exists for the accumulation of p53 protein in these T-cell disorders. The oncogenic effect of the accumulating wild-type protein has been reported in other malignancies. Whether haploidy resulting from p53 deletion contributes to this mechanism has yet to be determined. Alternatively, the frequent loss of the p53 gene could be associated with the deletion of an adjacent gene, which could be involved in the pathogenesis of these diseases.     

端粒酶催化亚单位和p53基因在大肠癌中表达的研究

目的　研究端粒酶催化亚单位 (hTERT)和p5 3基因在大肠癌组织中的表达 ,进而探讨大肠癌发生过程中端粒酶活化的分子机制。方法　分别采用原位逆转录聚合酶链反应 (RT PCR)和端粒重复序列扩增 (TRAP)法检测 46例大肠癌及其相应正常组织中hTERTmRNA表达与端粒酶活性。用免疫组化S P法测定上述组织标本中的p5 3蛋白表达。结果　hTERTmRNA与端粒酶活性在大肠癌组织中阳性表达率分别为 87 0 % (4 0 /4 6)和 80 4% (3 7/4 6) ,均明显高于相应正常组织 (P <0 .0 1)。大肠癌中hTERYmRNA表达与端粒酶活性明显相关 (r=0 .696,P <0 .0 1)。p5 3蛋白在大肠癌中阳性表达率为 67 4% (3 1/4 6) ,而正常组织未见阳性表达 ,二者比较差异有显著性 (P <0 .0 1)。大肠癌组织p5 3蛋白表达与hTERTmRNA表达或端粒酶活性无显著相关性 (P >0 .0 5 )。结论　端粒酶激活与大肠癌的发生密切相关 ,hTERTmRNA表达上调可能在大肠癌端粒酶活性调节中发挥重要作用。p5 3蛋白表达增强可能与端粒酶激活无直接相关     

胃癌组织中hPOT1和p53表达及其临床意义

目的探讨人端粒保护蛋白1（hPOT1）和p53在胃癌发生发展中的作用及机制。方法采用免疫组化SP法检测53份胃癌组织标本（观察组）及10份正常胃黏膜组织标本（对照组）hPOT1和p53蛋白表达;分析其与胃癌病理参数的关系。结果观察组hPOT1和p53蛋白阳性率均显著高于对照组P〈0.05;hPOT1表达与胃癌组织学分型、分化程度及浸润深度有关（P〈0.05）。p53表达与肿瘤浸润深度有关,P〈0.05;观察组hPOT1与p53蛋白表达呈正相关,P〈0.05。结论 hPOT1和p53参与了胃癌的发生、发展;联合检测hPOT1和p53蛋白表达有助于判断胃癌患者的预后。     

p53与人类肺癌关系研究的进展

p53基因是目前人类所发现的与肿瘤发病相关性最大的抑癌基因(tumorsuppressorgene,TSG)。p53基因的点突变、缺失及灭活在肺癌的发生和进展过程中起着关键性的作用。随着各项研究的不断进展以及高新检测技术的出现,p53在肺癌的早期诊断中的价值得到进一步的肯定。同时,利用p53进行基因治疗及评价肺癌患者预后的研究也逐渐开展起来并取得一定成效。因此深入探讨p53基因与人类肺癌的关系具有重大的意义。本文就p53与人类肺癌关系研究的进展作一论述。     

Correlation of p53 gene mutation and expression of P53 protein in cholangiocarcinoma

AIM: To characterize the tumor suppressor gene p53 mutations and study the correlation of p53 gene mutation and the expression of P53 protein in cholangiocarcinoma. METHODS: A total of 36 unselected, frozen samples of cholangiocarcinoma were collected. p53 gene status(exon 5-8) and P53 protein were examined by automated sequencing and immunohistochemical staining, combined with the clinical parameters of patients. RESULTS: p53 gene mutations were found in 22 of 36 (61.1%) patients. Nineteen of 36 (52.8%) patients were positive for P53 protein expression. There were significant differences in extent of differentiation and invasion between the positive and negative expression of P53 protein. However, there were no significant differences in pathologic parameters between the mutations and non-mutations. CONCLUSION: The alterations of the p53 gene evaluated by DNA sequence analysis is relatively accurate. Expression of P53 protein could not act as an independent index to estimate the prognosis of cholangiocarcinoma.     

Mina53在结肠癌组织中的表达意义及与肿瘤增殖的关系

目的:研究Mina53在结肠癌中的表达及与各临床病理特征和肿瘤增殖活性的关系.方法:运用实时定量PCR分别检测51例结肠癌、19例结肠腺瘤和20例正常结肠组织Mina53mRNA的表达,及结肠癌组织中Ki67mRNA的表达.结果:结肠癌、结肠腺瘤和正常结肠组织中Mina53mRNA的表达水平分别为1.369±0.874、0.453±0.233、0.347±0.128,结肠癌组织Mina53mRNA的表达明显高于结肠腺瘤及正常结肠组织;而与肿瘤的组织分化程度、临床分期、远处转移和淋巴结转移均相关(均P<0.05);结肠癌中Ki67mRNA表达水平为1.117±0.805,通过相关分析Mina53mRNA的表达与Ki67mRNA呈正相关(r=0.727,P<0.01).结论:Mina53在结肠癌中高表达,其表达与肿瘤的增殖活性相关,在结肠癌发生发展中Mina53可能起着重要作用.     

结肠癌血管内皮生长因子与微血管密度和p53的关系

目的探讨血管内皮生长因子(VEGF)在结肠癌中的表达及其与微血管密度(MVD)和p53之间的关系.方法用免疫组化SABC法检测68例结肠癌组织不同区域VEGF、MVD和p53的阳性表达.结果结肠癌区VEGF、MVD和p53的表达明显高于癌旁区和正常区.结肠癌组织VEGF及p53的表达与肿瘤浸润深度、淋巴结转移、远处转移、血管侵犯及Dukes分期密切相关,而与组织学分型无关.p53(+)或VEGF(+)组MVD(34.6±12.2;31.2±12.6)均显著高于p53(-)或VEGF(-)组(15.0±7.9;12.7±6.3,P＜0.01);VEGF和p53均为阳性时,MVD值最大(36.5±11.9,P＜0.01).MVD记数与VEGF表达明显相关(P＜0.01),p3表达与VEGF表达和MVD记数均显著相关(P＜0.01).结论在结肠癌血管生成过程中,可能存在p53-VEGF调节旁路,p53基因在调控肿瘤血管形成方面起重要作用.     

非小细胞肺癌患者呼出气冷凝液中p53基因突变检测的研究

目的 探讨非小细胞肺癌(NSCLC)患者呼出气冷凝液(EBC)中p53基因突变检测的临床意义.方法 采用PCR结合DNA测序法,检测53例NSCLC患者(治疗前)EBC中p53基因第5、6、7、8外显子的突变情况,32名健康体检者EBC标本作为对照.结果 肺癌组(治疗前)EBC标本中扩增到p53基因26例,其中10例检...     

非小细胞肺癌患者呼出气冷凝液中p53蛋白检测的临床意义

Objective To study the clinical significance of the detection of p53 protein in exhaled breath condensate (EBC) of patients with non-small cell lung cancer (NSCLC). Methods EBC and plasma of 98 patients with NSCLC were collected,p53 protein expression in EBC and plasma was detected by enzyme-linked immunosorbent assay,and the data were compared with those of 98 healthy controls. p53 protein expression in cancer tissue of 98 patients with NSCLC was detected by immunohistochemistry. p53 protein expression in EBC and plasma and positive expression rate of p53 protein in cancer tissue were compared among patients with different lung cancer type,stage,histologic type,tumor size,and lymph node metastasis,smoking history. The specificity and sensitivity of diagnosis of p53 protein in patients with NSCLC were analyzed by ROC curve. Results ① The level of p53 protein in EBC of patients with NSCLC was significantly higher than that in healthy control group [(233.99±7.91) ng/L vs ( 130. 26 ± 4. 73) ng/L,P ＜0. 01]. The level of p53 protein in serum of patients with NSCI.C was significantly higher than that in healthy control group [(292. 58 ± 8. 79) ng/L vs (141. 66±3. 33) ng/L,P ＜0. 01]. ② The level of p53 protein in EBC of patients with central lung cancer was higher than that in patients with peripheral lung cancer [(248. 22 ± 8. 58) ng/L vs (215. 78 ± 6.61) ng/L,P＜0. 01]. ③The level of p53 protein in EBC of patients with positive immunostaining group was higher than that in negative group [(249.77 ± 8.07) ng/L vs (216.86 ± 7.44) ng/L,P ＜ 0. 05]. ④The level of p53 protein in serum of smokers was significantly higher than that in non-smokers [(310.18 ± 9.04) ng/L vs (254. 55 ± 6. 91) ng/L,P ＜0. 01]. ⑤The positive expression rate of p53 protein in cancer tissue was 47. 96% (47/98). ⑥The sensitivity and specificity of diagnosis of p53 protein were 95. 90% and 90. 04% in plasma,and those were 92. 90% and 79. 59% in EBC. The cut off values of p53 protein were respectively 175. 68 ng/L and 166. 26 ng/L in EBC and serum. Conclusions The detection of p53 protein in EBC of patients with NSCLC is helpful for the diagnosis of lung cancer.