COX-2与突变型p53蛋白在乳腺癌组织中的表达及临床意义

目的研究COX-2蛋白和突变型p53蛋白在乳腺癌组织中的表达情况,探讨两者在乳腺癌发生、发展中的作用、相互关系及与临床病理学特征之间的关系。方法运用链霉菌抗生物素蛋白-过氧化物酶免疫组织化学方法（S-P）对99例乳腺癌组织中COX-2蛋白和突变型p53蛋白的表达进行检测。结果99例乳腺癌中COX-2蛋白表达阳性率为69.7%（69/99）,COX-2蛋白表达与患者年龄、原发肿瘤大小、腋淋巴结转移状况、TNM临床分期、激素受体状况均无显著相关（P〉0.05）,而与C-erbB-2蛋白表达呈显著相关（P〈0.05）。99例乳腺癌中突变型p53蛋白表达阳性率为48.5%（48/99）,突变型p53蛋白表达与患者年龄、TNM临床分期、激素受体状况无显著相关（P〉0.05）,而与原发肿瘤大小、腋淋巴结转移状况、C-erbB-2蛋白表达呈显著相关（P〈0.05）。COX-2蛋白表达与突变型p53蛋白在乳腺癌组织中的表达呈正相关（r=0.288,P〈0.05）,两者共表达与肿瘤大小、腋淋巴结转移状况呈显著相关（P〈0.05）。结论COX-2蛋白和突变型p53蛋白在乳腺癌组织中高表达,COX-2蛋白与突变型p53蛋白在乳腺癌组织中的表达呈正相关,两者在乳腺癌的发生、发展中可能起协同作用,是反映乳腺癌生物学行为的重要指标。     

延边地区乳腺癌中Ki-67、COX-2和p53的表达及意义

[目的]探讨乳腺癌中Ki-67、COX-2和p53表达及意义。[方法]应用免疫组化方法检测51例乳腺癌中Ki-67、COX-2、p53、ER、PR和C-erb B-2的表达情况,并分析其与乳腺癌临床病理特征的关系。[结果](1)乳腺癌中Ki-67、COX-2和p53的阳性表达率分别为70.6%(36/51)、64.7%(33/51)和66.7%(34/51);C-erb B-2、ER和PR的阳性表达率分别为23.5%(12/51),70.6%(36/51)和74.5%(38/51)。(2)Ki-67、COX-2和p53的表达与乳腺癌患者年龄、肿瘤大小、临床分期和病理类型无关,与淋巴结转移有关(P均<0.05)。(3)Ki-67、COX-2、p53表达与ER、PR水平呈负相关,而与C-erb B-2水平呈正相关。(4)COX-2与Ki-67及p53表达呈正相关。[结论]Ki-67、COX-2和p53的在乳腺中高表达,可能与乳腺癌的发生发展有关。     

Nm23-H1和p53基因在乳腺癌细胞增殖及转移评估中的价值研究

目的探讨乳腺癌中nm23-H1、p53基因与肿瘤细胞增殖活性、淋巴结转移之间的关系。方法应用免疫组化技术检测乳腺癌组织中nm23-H1、p53基因蛋白及增殖指标k i-67的表达,结合临床及病理指标,探讨其临床意义。结果乳腺癌组织中nm23-H1、p53蛋白阳性表达率分别为50.8%(61/120)和60.0%(72/120),nm23-H1蛋白的表达与增殖程度(k i-67)和腋窝淋巴结转移有关,k i-67低增殖组nm23-H1阳性表达率为68.0%(49/72),而k i-67高增殖组nm23-H1阳性表达率则为25.0%(12/48),差异有显著性(P<0.05)。无合并淋巴结转移组中nm23-H1阳性表达率为72.2%(39/54),明显高于淋巴结转移组的阳性率33.3%(22/66)(P<0.05)。p53蛋白表达与雌激素受体有关,雌激素受体阳性组p53阳性阳性表达率为55.8%(47/86),阴性组阳性表达率为73.5%(25/34),差异有显著性(P<0.05)。结论nm23-H1和p53基因均与乳腺癌生物学行为有关,检测它们在乳腺癌中的表达可用来评估肿瘤是否具转移和侵袭能力。     

COX-2、p53和C-erbB-2在乳腺癌组织中的表达及其临床意义

目的:探讨COX-2、p53和C-erbB-2与乳腺癌的关系.方法:用免疫组化方法检测96例乳腺癌标本中COX-2、p53和C-erbB-2的表达情况并结合临床病理特征分析.结果:三者在乳腺癌组织中均表达阳性,且三者阳性表达与淋巴结转移、肿瘤直径、ER阴性、乳腺癌临床分期有关.提示三者表达均可作为判断乳腺癌预后的指标,联合检测可更好的评价乳腺癌的预后.同时p53和C-erbB-2阳性表达在COX-2阳性表达的乳腺癌标本中表达尤为明显.结论: COX-2和p53、C-erbB-2阳性表达之间可能存在某种互调机制,为COX-2特异性免疫抑制剂治疗乳腺癌提供了新的思路.     

乳腺癌组织DAPK和p53及Bc1-2表达及其相互关系的研究

目的:检测乳腺癌组织中死亡相关蛋白激酶(DAPK)、p53和Bcl-2表达,探讨DAPK、p53和Bcl-2在乳腺癌组织中的作用及其相互关系。方法:用免疫组化SP法检测42例乳腺增生组织和68例乳腺浸润性癌组织中DAPK、p53和Bcl-2的表达水平,分析它们与乳腺癌临床病理的关系。结果:p53蛋白在乳腺增生组织中的表达为阴性,在乳腺癌组织中阳性表达率为51.5%(35/68);p53的阳性率与乳腺癌的组织学分级、淋巴结转移呈正相关。乳腺癌组织中Bcl-2阳性表达率为69.1%(47/68),明显高于乳腺增生组织;Bcl-2的阳性率与乳腺癌的肿瘤大小、淋巴结转移呈负相关。DAPK在乳腺癌组织中的阳性表达率为42.6%(29/68),明显低于乳腺增生组织;DAPK的阳性率与乳腺癌的病理分型、组织学分级、淋巴结转移、p53及Bcl-2呈负相关。结论:DAPK、p53和Bcl-2蛋白可作为预测乳腺癌生物学行为的参考指标。DAPK可能抑制乳腺癌的侵袭转移,这个作用可能与p53、Bcl-2相关。     

EZH2和p53在乳腺癌中的表达及相关性探讨

目的：研究乳腺癌中EZH2和p53表达及其相关性.方法：用免疫组织化学方法检测54例乳腺癌组织中EZH2和p53的表达情况,分析与临床病理特征之间的关系并探讨二者的相关性.结果：乳腺癌中EZH2表达阳性率48%（26/54）,EZH2表达与肿瘤大小、淋巴结转移、病理分级、ER受体相关,而与年龄、临床分期、PR受体不相关.在p53阳性的25例乳腺癌患者中,16例EZH2表达阳性,表达率64%（16/25）,p53阴性表达的29例中,9例EZH2表达阳性,表达率31%（9/29）,两者比较有相关性（P=0.03）.结论：EZH2在乳腺癌中表达增加且与p53相关,提示乳腺癌中EZH2与p53可能相互协调,促进乳腺肿瘤的发生发展.     

非小细胞肺癌组织COX-2和p53表达及其临床意义的探讨

目的:探讨COX-2 和突变性p53蛋白在非小细胞肺癌(NSCLC)发生、发展中的作用机制及两者之间的相关性.方法:流式细胞仪检测80例NSCLC组织和20例癌旁正常肺组织中COX-2 蛋白、突变型p53蛋白的表达情况.结果:NSCLC组织中COX-2蛋白较正常组织高表达,P<0.01.COX-2表达与有无淋巴结转移(P=0.002)和肿瘤大小(P=0.045)有关,与NSCLC患者性别、TNM分期、分化程度和组织学类型无关,P>0.05.NSCLC组织中p53蛋白较正常组织高表达,P<0.01.p53蛋白表达与有无淋巴结转移(P=0.01)有关;而与NSCLC患者性别、肿瘤的大小、TNM分期、肿瘤分化程度和组织学类型无关,P>0.05.NSCLC组织中p53和COX-2蛋白同时阳性表达率为47.82%(22/46),p53阴性COX-2蛋白阳性表达率为58.82%(20/34),两者表达无相关性,P=0.33.结论:COX-2的过表达及p53蛋白突变与NSCLC的发生发展有关,两者之间无相关性.     

Acsl4在浸润性乳腺癌组织中的表达及其临床意义

目的:探讨Acsl4在浸润性乳腺癌组织中的表达及其临床意义。方法:采用免疫组织化学法检测108例浸润性乳腺癌组织中Acsl4的表达。结果:108例浸润性乳腺癌组织中,33例(30.6%)阳性表达,75例(69.4%)阴性表达。组织学G3级的乳腺癌组织中Acsl4阳性率为42.3%(22/52),高于G1+G2级的阳性率(19.6%,11/56),差异具有统计学意义(P<0.05)。ER阳性组织的Acsl4的阳性率15.8%(6/38),低于ER阴性的病例(38.6%,27/70),差异具有统计学意义(P<0.05)。Acsl4的表达与患者年龄、肿瘤大小、淋巴结是否转移、HER2、PR、p53、Ki67的表达情况无统计学意义的相关性(P均>0.05)。结论:Acsl4在浸润性乳腺癌组织中存在异常表达,其阳性表达与乳腺癌患者组织学分级较高及ER阴性表达密切相关。     

乳腺癌组织中COX-2与MDR1/P-gp表达的相关性研究

目的:探讨环氧化酶-2(COX-2)蛋白与P糖蛋白(P-gp)在乳腺癌组织中表达的相关性。方法:应用免疫组织化学染色法,检测32例乳腺癌组织中COX-2蛋白与P-gp蛋白的表达情况。结果:32例乳腺癌组织中COX-2表达阳性率为62·5%(20/32),P-gp表达阳性率为46·9%(15/32),两者表达呈正相关性(r=0·598,P<0·05)。结论:乳腺癌组织中COX-2与P-gp表达呈正相关,COX-2可干预P-gp的表达并参与乳腺癌多药耐药(MDR)的调节。     

乳腺癌组织p53蛋白与P-耐药糖蛋白表达水平的关系

目的 :研究p53蛋白表达与P 糖蛋白 (P gp)的关系。方法 :用免疫组织化学法检测 50例乳腺癌组织中p53蛋白及P gp表达。结果 :乳腺癌组织中p53阳性表达率为 6 4 % ,P gp阳性表达率为50 % ;p53阳性组的P gp表达率 (6 5.6 % ,2 1/ 32 )显著高于p53阴性组 (2 2 .2 % ,4 / 18) ,(P <0 .0 0 5) ,p53表达与P gp有关。结论 :p53表达可引起多药耐药基因 (MDR1)编码产物P gp表达增高 ,从而使乳腺癌细胞获得多药耐药 (MDR)表型 ;P gp不能作为评判乳腺癌预后和生物学行为的独立指标。     

乳腺癌中环氧合酶2与p53的表达及其与预后的关系

目的探讨环氧合酶2（COX．2）和p53蛋白在乳腺癌组织中的表达及其与乳腺癌预后的关系。方法用免疫组化法检测152例乳腺癌组织和16例正常乳腺组织COX．2和p53蛋白表达情况。通过生存分析研究它们与预后的关系。结果COX．2与p53在正常乳腺组织均不表达。COX．2和p53蛋白在乳腺癌组织中的表达率分别为58．6％（89／152）、61．2％（93／152）,二者呈显著相关性（r=0．426,／9〈0．01）;二者表达在Ⅰ、Ⅱ级乳腺癌组织中均显著相关（r值分别为0．414,0．381,均P〈0．01）,在Ⅲ级乳腺癌组织中二者无相关性（／9〉0．05）。I、Ⅱ、Ⅲ、Ⅳ期乳腺癌COX-2、p53表达均显著相关（r值分别为0．659,O．557,0。390,0．685,均P〈0．01）。两者表达与淋巴结、远处转移均相关（均／9〈0．05）。COX-2高表达组的5年无进展生存（PFS）率显著低于低表达者,但p53高表达组与低表达组的5年PFS率差异无统计学意义。COX-2与p53均高表达者的5年PFS低于COX-2或p53单一高表达者,亦低于两者均双低表达者。结论COX－2和p53的表达与临床分期、淋巴结转移、远处转移、病理分级等临床预后不良因素有关。检测COX-2和p53对乳腺癌的预后有重要价值。     

Expression of cyclooxygenase-2 in primary and remnant gastric carcinoma: comparing it with p53 accumulation,Helicobacter pylori infection,and vascular endothelial growth factor expression

BACKGROUND AND OBJECTIVES: Cyclooxygenase-2 (COX-2) expression may contribute to the synthesis of prostanoids, which have been related to carcinogenesis and tumor progression. It is well known that the gastric remnant is at greater risk of the development of gastric cancer than is the whole stomach; incidence rates for gastric cardia adenocarcinoma are rising in the United States and Europe. Our objective was to determine the involvement of COX-2 in primary and remnant gastric cancer tissues as well as in adjacent noncancerous mucosa. METHODS: We investigated the expression of COX-2 in 91 human gastric cancer tissue and adjacent noncancerous mucosa samples (40 remnant gastric cancer, 37 gastric cardia cancer, and 14 gastric corpus and antrum cancer), using immunohistochemistry. In addition, p53 expression, Helicobacter pylori infection, and vascular endothelial growth factor in the tissues were evaluated by immunohistochemical staining and compared with COX-2 expression. RESULTS: There were no significant differences in clinicopathological data in the gastric cancer tissues. There was a significant relation between the expression of COX-2 and p53 in gastric cancer tissues (P = 0.0048). However, vascular endothelial growth factor expression and Helicobacter pylori infection showed no correlation with the expression of COX-2. In the case of adjacent noncancerous mucosa, the positive rate of COX-2 expression was significantly higher in the remnant gastric cancers (75.0%) than in the primary gastric cancers (25.5%) (P < 0.0001). CONCLUSIONS: This information may help in the analysis of the carcinogenesis of gastric cancer; there is also a possibility that the COX-2 selective inhibitor to the remnant gastric cancer has a chemopreventive effect.     

Loss of FHIT expression in breast cancer is correlated with poor prognostic markers.

OBJECTIVE: The fragile histidine triad (FHIT) gene is a putative tumor suppressor gene that is thought to be involved in the carcinogenesis of breast cancer. Loss of FHIT expression has been observed in up to 72% of breast cancers and has been associated with increased p53, a high proliferation index, and increased tumor size and grade. However, loss of FHIT expression has not been investigated in association with apoptosis and cyclooxygenase-2 (COX-2) expression in breast cancer. Furthermore, expression of FHIT in primary breast tumors and their metastatic axillary lymph nodes has also not been previously described. The purpose of this study was to evaluate the expression of FHIT, COX-2, bcl-2, and p53 in primary breast tumor tissue; correlate their expression with known clinical and pathologic markers; and in cases when tissue was available, evaluate the expression of FHIT and COX-2 in the corresponding metastatic axillary lymph node in the same patient. METHODS: Primary breast tumor specimens from 80 patients were examined for the presence of FHIT, COX-2, bcl-2, and p53 expression by immunohistochemistry using standard methods. When tissue was available, the expression of FHIT and COX-2 was also evaluated in the corresponding metastatic axillary lymph node specimen. RESULTS: FHIT expression in primary breast tumors was 56%. There was a significant correlation between FHIT expression in primary breast tumor and bcl-2 expression (P = 0.017). We also observed a significant inverse correlation between FHIT expression in primary breast tumor tissue and p53 expression (P = 0.023) in lymph node-negative cases. A significant inverse correlation between FHIT expression in the primary tumor and Ki-67 (P = 0.009) was also observed in lymph node-negative cases. FHIT expression in primary tumors correlated with FHIT expression in the metastatic lymph node (52.5%; P = 0.001). FHIT expression in primary tumors did not correlate with COX-2 expression. CONCLUSION: Our results suggest that loss of FHIT expression in breast cancer is associated with poor prognostic features. Furthermore, loss of FHIT expression is also seen in metastatic axillary lymph node. The prognostic and predictive value of these findings needs to be further evaluated in larger trials with longer follow-up.     

上皮性卵巢癌组织中环氧化酶-2的表达与化疗耐药的相关性研究

目的:探讨上皮性卵巢癌组织中环氧化酶-2(cyclooxygenase-2,COX-2)表达与化疗耐药的关系,以及与p53表达的相关性。方法:用免疫组化SP法检测108例上皮性卵巢癌组织和20例正常卵巢组织中COX-2和p53表达。结果:COX-2和p53在上皮性卵巢癌组织中阳性表达率分别为48.1%和59.3%,正常卵巢组织均未见表达,差异有极显著性(P<0.01);COX-2和p53表达呈显著正相关(P<0.01)。COX-2表达与患者病理类型、临床分期、病理分级及年龄无关,与术后残留灶直径有显著相关性(P<0.01)。COX-2和p53阳性表达率,耐药组和非耐药组相比均有显著差别(P<0.01)。多因素分析显示,卵巢癌患者COX-2、p53表达和术后残留灶直径是与化疗耐药密切相关的独立因素。结论:COX-2表达是与化疗耐药相关的独立危险因素。COX-2过表达与抑癌基因p53的突变可能具有相互促进作用,在卵巢癌化疗耐药中起重要作用。     

乳腺癌血清VEGF水平与癌组织中VEGF和COX-2表达及微血管密度的关系

目的探讨乳腺癌患者血清血管内皮生长因子(sVEGF)水平与乳腺癌血管生成的关系。方法采用酶联免疫吸附试验(ELISA)检测68例乳腺癌、35例乳腺良性病变和20例健康女性的sVEGF水平,免疫组化S-P法检测相应乳腺癌组织中VEGF、环氧合酶-2(COX-2)及微血管密度(MVD)表达水平,并分析sVEGF水平与VEGF、COX-2及MVD表达的关系。结果(1)健康女性组、乳腺良性病变组和乳腺癌组sVEGF浓度中位数分别为105.93、150.82和306.51 pg/ml,乳腺癌组明显高于健康女性组。(2)乳腺癌组VEGF和COX-2表达阳性率分别为67.6%和44.1%,乳腺良性病变组VEGF和COX-2表达阳性率分别为42.9%和11.4%,两组间差异有统计学意义(P值分别为0.015和0.002)。(3)乳腺癌患者sVEGF水平与癌组织中VEGF、COX-2及MVD表达均呈正相关。(4)乳腺癌患者中,VEGF表达阳性组COX-2阳性率(65.21%)明显高于VEGF表达阴性组(18.18%); COX-2表达阳性组MVD(22.94±5.51)明显高于COX-2表达阴性组(10.30±4.42)。结论乳腺癌患者sVEGF水平明显增高于健康女性,并与癌组织中VEGF、COX-2及MVD表达呈正相关。     

Expression of cyclooxygenase-2 and its relationship to p53 accumulation in ovarian adenocarcinomas

To investigate cyclooxygenase-2 (COX-2) expression and its relationship to p53 accumulation in ovarian adenocarcinomas, COX-2 and p53 protein expressions were examined by immunohistochemistry in 86 ovarian adenocarcinomas and six normal ovaries. In addition, COX-2 mRNA expression level was examined by semi-quantitative PCR in 36 ovarian adenocarcinomas. Neither COX-2 expression nor p53 accumulation were detected in normal ovarian surface epithelium or germinal inclusion cyst epithelial cells. In contrast, COX-2 protein expression was detected in 31.4% of adenocarcinomas, and p53 protein accumulation was found in 30.2% of adenocarcinomas. A significantly higher COX-2 expression rate was observed in endometrioid adenocarcinomas than in either mucinous (p=0.019) or clear cell (p=0.021) adenocarcinomas, and a significantly higher p53 accumulation rate was observed in serous adenocarcinomas compared to clear cell adenocarcinomas (p=0.015). p53 accumulation correlated with advanced clinical stage (stage I vs. stage II/III/IV: p=0.007), whereas no correlation was found between COX-2 expression and clinical stage. There was a significant positive correlation between COX-2 expression and p53 accumulation status (p=0.003). Log-rank testing showed that p53 accumulation was significantly correlated with poor patient survival (p=0.004), whereas no correlation was found between COX-2 expression and survival. COX-2 mRNA expression was detected in 72.2% of ovarian adenocarcinomas, and a significant correlation between COX-2 mRNA expression status and immunoreactivity (p=0.023) was observed. These results suggest that COX-2 expression might play an important role in ovarian cancer development and that COX-2 expression in ovarian adenocarcinomas is frequently associated with p53 protein accumulation. COX-2 overexpression in ovarian cancer cells might partly be caused by dysfunctional p53.     

Cyclooxygenase-2 expression correlates with diminished survival in invasive breast cancer treated with mastectomy and radiotherapy

PURPOSE: To evaluate the relationship between cyclooxygenase-2 (COX-2) expression and pathologic features and outcome in invasive breast cancer. METHODS AND MATERIALS: Formalin-fixed, paraffin-embedded tumor specimens from 23 women with invasive breast cancer were stained for COX-2 expression. All women underwent mastectomy and locoregional radiotherapy. The distribution (percentage of positive staining cells) and intensity of COX-2 expression within the tumor cells were compared with clinical factors, including stage, grade, lymph node involvement, and outcome. RESULTS: For invasive breast cancer, the distribution and intensity of COX-2 tumor expression correlated significantly with diminished overall survival. The 5-year overall survival rate was 100% for patients with <75% of breast cancer cells expressing COX-2 compared with 49% for patients with > or =75% (p = 0.044). The 5-year overall survival rate was 100% for patients with COX-2 intensity <80 compared with 60% for patients with COX-2 intensity > or =80 (p = 0.018). The percentage and intensity of COX-2 expression also correlated significantly with disease-free survival. The percentage of cells expressing COX-2 was significantly greater in women <40 years old than in women > or =40 years old (81% vs. 59%, respectively, p = 0.04). CONCLUSION: Both the distribution and the intensity of COX-2 expression correlated significantly with disease-free and overall survival in patients with invasive breast cancer. Younger patients with invasive breast cancer may have a greater percentage of COX-2 expression in their tumors.     

Survivin在乳腺癌中的表达及其与p53的关系

目的:观察Survivin在乳腺癌及癌旁组织中的表达情况,探讨其与突变型p53基因表达的相关性。方法:用免疫组化SP法检测60例乳腺癌组织,60例癌旁乳腺正常组织中Survivin和p53的表达情况,分析其与腋窝淋巴结转移之间的关系。结果:60例乳腺癌组织中Survivin蛋白的阳性表达率为78.33%,明显高于癌旁正常组织(5.00%)(P<0.05),Survivin在p53阳性的乳腺癌组织中的表达率明显高于p53阴性组,Survivin的表达与乳腺癌的病理分级和淋巴结转移状况无显著相关。结论:乳腺癌组织中Survivin表达上调与乳腺癌的发生与发展密切相关,其表达与p53基因突变显著相关,两者可能协同作用参与乳腺癌的发生与发展。