Cyclooxygenase-2 Expression as a New Marker for Patients with Colorectal Cancer

PURPOSE: Epidemiologic studies indicate that the use of nonsteroidal anti-inflammatory drugs, which inhibit cyclooxygenase activity, reduce the risk of colorectal cancer. In addition, several studies demonstrate increased expression of cyclooxygenase-2 in human colorectal cancer tissues. However, the role of cyclooxygenase-2 expression in colorectal cancer has not yet been fully established. The aim of this study was to clarify the clinicopathologic significance of cyclooxygenase-2 expression in human colorectal cancer. METHODS: A total of 232 surgically resected colorectal cancer specimens were analyzed immunohistochemically with the use of a murine anti-human cyclooxygenase-2 monoclonal antibody. Cyclooxygenase-2 expression was then compared with clinicopathologic background and survival outcome. RESULTS: Cyclooxygenase-2 was expressed in the cytoplasm of the cancer cells but not in normal epithelium. Cyclooxygenase-2 expression was noted in 71.6 percent (166/232) of the cancer patients and correlated significantly with histologic type (P = 0.033), depth of invasion (P = 0.016), pathologic stage (P = 0.020), and metachronous liver metastasis (P = 0.001). Multivariate analysis for factors associated with metachronous liver metastasis showed that cyclooxygenase-2 expression was one of the independent risk factors, second only to lymph node metastasis. Patients with cyclooxygenase-2 expression showed a significantly poorer outcome compared with those without cyclooxygenase-2 expression (P = 0.002). CONCLUSION: Cyclooxygenase-2 expression in the primary lesion may be a useful marker for evaluating prognosis and liver metastasis in patients with colorectal cancer.     

Cyclooxygenase-2 Expression Correlates With Membrane-Type-1 Matrix Metalloproteinase Expression in Colorectal Cancer Tissue

Purpose Elevated expression of cyclooxygenase-2 has been found in colorectal cancer. One of the mechanisms through which cyclooxygenase-2 affects tumorigenesis is through its overexpression, which leads to increased invasiveness of cancer cells. A crucial step in this pathway is thought to be the induction of membrane-type-1 matrix metalloproteinase, which activates matrix metalloproteinase-2. However, to date there have been few clinicopathologic studies concerning cyclooxygenase-2-mediated invasiveness in human colorectal cancer tissues. Methods We performed immunohistochemical analysis of the respective antigens on colorectal cancer specimens obtained by surgical resections from 96 patients with colorectal cancer. Results Cyclooxygenase-2 and membrane-type-1 matrix metalloproteinase expression was positive exclusively in cancer cells in 88 cases (92 percent) and 23 cases (24 percent), respectively. All 23 cases expressing membrane-type-1 matrix metalloproteinase also expressed cyclooxygenase-2. Matrix metalloproteinase-2 expression was positive in cancer cells in 20 cases (21 percent) and stromal cells in 52 cases (54 percent). Expression of matrix metalloproteinase-2 in cancer cells correlated with lymphatic invasion and local recurrence. Statistically, a significant correlation was found between cyclooxygenase-2 and membrane-type-1 matrix metalloproteinase expression, and membrane-type-1 matrix metalloproteinase and matrix metalloproteinase-2 expression in cancer cells. There was no association between cyclooxygenase-2 expression and matrix metalloproteinase-2 expression. However, immunostaining of serial sections revealed that in the majority of cases examined, nearly 100 percent of cancer cells expressing matrix metalloproteinase-2 also coexpressed cyclooxygenase-2. Conclusions This study indicates strong association between both cyclooxygenase-2 and membrane-type-1 matrix metalloproteinase expression, and membrane-type-1 matrix metalloproteinase and matrix metalloproteinase-2 in colorectal cancer. These results support our thesis of a direct correlation between cyclooxygenase-2 and membrane-type-1 matrix metalloproteinase expression—with consequent association between cyclooxygenase-2 and matrix metalloproteinase-2 activation, and tumor invasiveness andrecurrence in certain cases of colorectal cancer. Presented at the meeting of the American Gastroenterological Association, Digestive Diseases Week, May 14 to 19, 2005, Chicago, Illinois. Reprints are not available.     

Cyclooxygenase-2 expression as a predictor of outcome in colorectal carcinoma

AIM: To correlate cyclooxygenase-2 (COX-2) expression profile with clinical and pathological variables to assess their prognostic/predictive value in colorectal carcinoma (CRC).METHODS: Archival tumor samples were analyzed using immunohistochemistry for COX-2 expression in 94 patients with CRC. Patients were diagnosed and treated at the Departments of Surgery and Oncology, King Abdulaziz University Hospital, Saudi Arabia.RESULTS: Fifty-six percent of the tumors showed positive cytoplasmic COX-2 expression, whereas 44% of cases were completely COX-2-negative. There were no significant correlations between COX-2 expression and sex, age, grade or tumor location. However, COX-2 expression revealed a significant correlation with tumor stage (P = 0.01) and distant metastasis (P = 0.02), and a borderline association with lymph node involvement (P = 0.07). Tumors with high COX-2 expression showed a higher recurrence rate than tumors with no expression (P < 0.009). In univariate Kaplan-Meier survival analysis, there was a significant (P = 0.026) difference in disease-free survival between COX-2-positive and negative tumors in favor of the latter. COX-2 expression did not significantly predict disease-specific survival, which was much shorter for COX-2-positive tumors. In multivariate (COX) models, COX-2 did not appear among the independent predictors of disease-free survival or disease-specific survival.CONCLUSION: COX-2 expression seems to provide useful prognostic information in CRC, while predicting the patients at high risk for recurrent disease.     

5-Lipoxygenase is Coexpressed with Cox-2 in Sporadic Colorectal Cancer: A Correlation with Advanced Stage

Purpose It has been extensively documented that the cyclooxygenase inducible form and 15-lipoxygenase are implicated in colorectal carcinogenesis. Nonetheless, the role of other enzymes involved in the arachidonic acid metabolism, such as 5-lipoxygenase, in colorectal neoplasms has not been fully ascertained. This study was designed to evaluate 5-lipoxygenase expression in sporadic colorectal adenocarcinomas by using immunohistochemistry and to analyze its potential correlations with clinicopathologic parameters and with cyclooxygenase-2 expression. Methods Expression of 5-lipoxygenase and cyclooxygenase-2 were evaluated by immunohistochemistry in 50 surgically resected sporadic colorectal adenocarcinomas (28 male and 22 female patients age range, 47–88 (mean age, 69 ± 8) years). The chi-squared and Spearman correlation tests were used to analyze correlations with clinicopathologic characteristics and to evaluate any relationships between expression of the two enzymes. P values <0.05 were considered statistically significant. Results 5-Lipooxygenase and cyclooxygenase-2 immunostaining was found in the cytoplasm of neoplastic cells in 41 (82 percent) and in 43 cases (86 percent), respectively. Spearman correlation test demonstrated a positive correlation in the expression of the two enzymes. A statistically significant correlation also was observed between 5-lipoxygenase expression and tumor stage and lymph node metastasis, whereas no significant correlations emerged regarding cyclooxygenase-2 expression and clinicopathologic parameters. Conclusions Our study demonstrates that 5-lipoxygenase is expressed in colorectal adenocarcinomas in association with cyclooxygenase-2 expression. Moreover, an elevated expression of this enzyme seems to be significantly correlated with tumor aggressiveness. Further studies would clarify the need for target therapies inhibiting both metabolic pathways in such tumors. Supported by the grants from the University of Messina, Messina, Italy. Presented at the meeting of the Italian Society of Anatomic Pathology and Diagnostic Cytopathology (SIAPEC), Venice, Italy, October 4 to 5, 2006.     

大肠癌和大肠腺瘤COX-2和BFGF表达的意义

目的:研究COX-2和BFGF在大肠癌及大肠腺瘤组织中的表达及意义．方法:采用免疫组化SP方法检测了手术切除的大肠癌49例,腺瘤性息肉25例,正常大肠黏膜组织20例中的COX-2和BFGF表达．结果:COX-2和BFGF在大肠癌中的表达阳性率分别为59．2％和69．3％,在腺瘤性息肉的表达率为52．0％和56．0％,COX-2和BFGF在大肠癌组织与腺瘤性息肉中表达无显著性差异(P>0．05):正常肠黏膜中未检出COX-2和BFGF．COX-2和BFGF在大肠癌中表达与性别,年龄,肿瘤大小,肿瘤位置,分化程度无关(P>0．05)．但与肿瘤Dukes分期有关,C,D期高于A,B期(81．5％vs 54．5％,P<0．05),淋巴结转移之间具有显著性差,有异淋巴结转移高于无淋巴结转移(81．5％vs 54．5％,P<0．05)．肠癌组织中COX-2、BFGF表达二者间有相关性(r= 0．349,P<0．05)．结论:COX-2、BFGF在大肠癌组织及大肠腺瘤中的表达水平增高,在大肠腺瘤恶变及大肠癌的发生发展过程中起协同作用,共同促进肿瘤的发生．     

COX-1和COX-2在结直肠腺瘤中的表达

目的观察COX-1和COX-2在结直肠腺瘤中的表达情况。方法16例经病理证实的散发性结直肠腺瘤活组织检查标本，15例肠镜检查无明显病变的IBS患者肠黏膜活组织检查标本。免疫组化染色观察COX-1和COX-2表达水平的变化。结果COX-2在结直肠腺瘤组织中的表达异常增高（P〈0．05），而COX-1在正常组织和腺瘤中的表达水平没有明显的变化。结论在结直肠腺瘤组织中，COX-2表达明显升高，提示COX-2参与结直肠腺瘤的发生和发展。     

Bcl-2与PCNA在大肠腺瘤和大肠癌中的表达

目的　探讨增殖细胞核抗原 (proliferatingcellnuclearantigen ,PCNA)与原癌基因bcl 2在大肠腺瘤和大肠癌中的表达变化以及与大肠腺瘤和大肠癌的发生、发展的关系。方法　采用免疫组化S P法 ,分别检测PCNA与bcl 2在 18例大肠腺瘤和 18例大肠癌中的表达。结果　PCNA在大肠腺瘤和大肠癌中的标记指数分别为 65 95± 12 94%和 84 5 3± 10 3 9% ,两者均明显高于正常肠粘膜中的指数 ,P <0 0 0 1,两者相比有显著性差异 ,P <0 0 1。Bcl 2在大肠腺瘤和大肠癌中的表达分别为 81 10± 10 0 0 %和 65 78±12 95 % ,两者均明显高于正常肠粘膜中的表达P <0 0 0 1。两者相比有显著性差异 ,P <0 0 1。结论　大肠癌的癌前病变腺瘤中存在活跃的细胞增殖 ,而且同时有细胞凋亡的改变 ,细胞增殖和细胞凋亡的调控失常共同导致了肿瘤的发生。     

Moderate Alcohol Consumption Protects Against Colorectal Adenomas in Smokers

Background Although some studies have shown an association between alcohol consumption and colorectal adenomas, the effect of moderate alcohol consumption is not well defined, nor is the interaction between alcohol and smoking. Aim To investigate the relationship between different levels of alcohol consumption and colorectal adenomas and to determine whether smoking modifies this relationship. Methods Eligible patients who underwent a complete colonoscopy were included (179 cases and 466 controls). Alcohol consumption was obtained from a lifestyle questionnaire. Patients were divided into three groups: (1) Abstainers: 0 drinks/week; (2) Moderate drinkers: > 0 to <7 drinks/week; (3) Heavy drinkers: > 7 drinks/week. Odds ratios (OR) were calculated using logistic regression, controlling for gender, age, body mass index, use of non-steroidal anti-inflammatory medications. Results were stratified by the number of years smoked. Results The proportion of patients with adenomas was 29.6% in abstainers, 22.1% in moderate drinkers, and 36.7% in heavy drinkers. The relationship between alcohol consumption and colorectal adenomas varied significantly by smoking history. For individuals who had never smoked, heavy drinkers were at significantly increased odds of having an adenoma compared to moderate drinkers (OR 3.08; 95% CI: 1.50–6.32), while no difference was seen for abstainers (OR 0.99; 95% CI: 0.52–1.89). Similarly, among individuals who had smoked 1–14 years, heavy drinkers were at increased odds of having an adenoma compared to moderate drinkers (OR 2.61; 95% CI: 1.04–6.51), and no difference was seen for abstainers (OR 1.02; 95% CI: 0.33–3.10). Somewhat unexpectedly, among individuals who had smoked for 15 or more years, abstainers were at increased odds of having an adenoma compared to moderate drinkers (OR 2.04; 95% CI: 0.91–4.59), while heavy drinkers were not at increased odds of having an adenoma (OR 0.73; 95% CI: 0.27–1.97). Conclusions Consumption of less than seven alcohol drinks per week does not increase the risk of having a colorectal adenoma. We found evidence in this study that moderate alcohol consumption among long-term smokers may potentially decrease the risk of an adenoma compared to abstainers.     

Cholecystectomy and the Risk of Colorectal Adenomas

Cholecystectomy has been identified as a risk factor for colorectal cancer, yet little attention has been given to the relationship between cholecystectomy and colorectal adenomas. Utilizing data collected in two large cross-sectional studies of colorectal adenoma risk factors, we examined the association between cholecystectomy and colorectal adenomas. In the adjusted logistic regression model, both men and women showed no effect of cholecystectomy on risk of colorectal adenomas (men: OR 0.67 [95% CI 0.30–1.47]; women: OR 1.46 [95% CI 0.92–2.29]). No effect was seen when examining the time since cholecystectomy for men. There was a slight association found for women who had a cholecystectomy less than 10 years prior (OR 2.02 [95% CI 1.06–3.87]) but no association was seen in women with cholecystectomy at least 10 years prior (OR 1.14 [95% CI 0.62–2.09]). Thus, we conclude that, although cholecystectomy is a risk factor for colorectal cancer, cholecystectomy is not a risk factor for colorectal adenomas.     

Cyclooxygenase-2 expression in primary human colorectal cancers and bone marrow micrometastases

BACKGROUND: Both the expressions of the inducible form of cyclooxygenase-2 and the presence of bone marrow micrometastases are poor prognostic markers in patients with colorectal carcinoma. AIMS: As cyclooxygenase-2 expression in these tumours is associated with increased metastatic potential in vitro, our objectives were to determine the relationship between cyclooxygenase-2 and haematogenous spread to bone marrow. PATIENTS AND METHODS: Thirty-two patients with resection of colorectal carcinoma were evaluated (median age: 69.5 years). Bone marrow was obtained from all patients from both iliac crests before manipulation of the primary tumour. The tumours were of varying stages at diagnosis (5 Dukes' A, 14 Dukes' B, 11 Dukes' C and 2 Dukes' D). Tumour sections were stained for cyclooxygenase-2 using the avidin-biotin immunohistochemical technique. Extent of staining was graded depending on the percentage of epithelial cells staining positive for cyclooxygenase-2. Micrometastases were detected by staining contaminant cytokeratin-18 positive cells in the bone marrow aspirates by either immunohistochemical (ARAAP) or immunological (flow cytometry) methods. Fisher's exact probability test was used to calculate statistical significance. RESULTS: Cyclooxygenase-2 expression in the primary tumour was detected in 72% of the patients. Twelve (38%) patients had bone marrow micrometastases detected by either immunohistochemistry or flow cytometry. Of the 12 patients who had bone marrow micrometastases, 8 tumours demonstrated increased expression of cyclooxygenase-2 protein (66.6%). In contrast, 9 out of the 20 (45%) patients in whom micrometastases were not detected expressed increased levels of cyclooxygenase-2 (P = 0.29). When dividing the patients into subgroups of localised (Dukes' A and B) versus disseminated (Dukes' C and D) disease, there was no further association between cyclooxygenase-2 expression and bone marrow micrometastases (P = 0.179 and 1.0). CONCLUSION: In this pilot study, there was no association between cyclooxygenase-2 expression and bone marrow micrometastases in patients with otherwise localised or disseminated disease.     

CCR2在结直肠癌的表达及意义

目的探讨大肠癌中CCR2蛋白的表达与肿瘤病理特征的关系。方法用免疫组织化学方法检测148例大肠癌患者手术切除大肠癌组织及66例癌旁对照组织中CCR2表达情况。结果大肠癌组织中CCR2的表达明显高于大肠正常组织（P〈0．01）,并且其表达强度与DukeC＋D期、肿瘤淋巴结转移、远处脏器转移以及较低的分化程度有关（各组中P〈0．01,差异具有统计学意义）;与年龄、性别、肿瘤发生部位以及肿瘤大小无关。结论CCR2的过表达在大肠癌发生、发展及转移的过程中可能发挥一定作用。CCR2可以作为大肠癌分化程度较低且伴淋巴结转移、肝转移的预测指标之一。     

Immunohistochemical Expression of Matrix Metalloproteinase-7 in Human Colorectal Adenomas Using Specified Automated Cellular Image Analysis System: A Clinicopathological Study

Background/Aim:

To evaluate the immunohistochemical expression of matrix metalloproteinase-7 (MMP-7) in colorectal adenomas, and to correlate this expression with different clinicopathological parameters.

Patients and Methods:

The study was retrospectively designed. Thirty three paraffin blocks from patients with colorectal adenoma and 20 samples of non-tumerous colonic tissue taken as control group were included in the study. MMP-7 expression was assessed by immunohistochemistry method. The scoring of immunohistochemical staining was conducted utilizing a specified automated cellular image analysis system (Digimizer).

Results:

The frequency of positive immunohistochemical expression of MMP-7 was significantly higher in adenoma than control group (45.45% versus 10%) (P value < 0.001). Strong MMP-7 staining was mainly seen in adenoma cases (30.30%) in comparison with control (0%) the difference is significant (P < 0.001). The three digital parameters of MMP-7 immunohistochemical expression (Area (A), Number of objects (N), and intensity (I)) were significantly higher in adenoma than control. Mean (A and I) of MMP-7 showed a significant correlation with large sized adenoma (≥ 1cm) (P < 0.05), also a significant positive correlation of the three digital parameters (A, N, and I) of MMP-7 expression with villous configuration and severe dysplasia in colorectal adenoma had been identified (P < 0.05).

Conclusion:

MMP-7 plays an important role in the growth and malignant conversion of colorectal adenomas as it is more likely to be expressed in advanced colorectal adenomatous polyps with large size, severe dysplasia and villous histology. The use of automated cellular image analysis system (Digmizer) to quantify immunohistochemical staining yields more consistent assay results, converts semi-quantitative assay to a truly quantitative assay, and improves assay objectivity and reproducibility.     

结肠癌及癌前病变组织中COX-2及VEGF的表达

目的: 探讨结肠癌及癌前病变中COX-2和血管内皮生长因子(VEGF)的表达意义.方法:应用免疫组织化学ABC法检测COX-2及VEGF在40例癌旁正常结肠黏膜和结肠癌、27例结肠腺瘤组织中COX-2和VEGF的表达.结果: 结肠腺瘤和结肠癌组COX-2阳性表达率明显高于癌旁正常结肠黏膜组(63.0%, 77.5% vs 0.0%, 0.0%;P<0.05). 结肠腺瘤和结肠癌组VEGF阳性表达率明显高于癌旁正常结肠黏膜组(70.4%, 80.0% vs 25.0%, 25.0%;P<0.05), 且二者表达有相关性(r = 0.411, P<0.01). 结论:COX-2和VEGF在结肠腺瘤及结肠癌中表达异常增高.     

氧化苦参碱对慢性心力衰竭大鼠心肌胞浆型磷脂酶A2、环氧合酶1、环氧合酶2、前列腺素I2合酶表达的影响

目的　探讨氧化苦参碱对异丙肾上腺素（ISO）诱导心力衰竭大鼠模型中心肌组织胞浆型磷脂酶A2（cPLA2）、环氧合酶1（COX-1）、环氧合酶2（COX-2）及前列腺素I2合酶（PGIS）的影响。方法　采用Sprague-Dawley大鼠皮下注射ISO（5　mg/kg）7天建立慢性心力衰竭大鼠模型。实验分为5组：正常对照组、ISO组、氧化苦参碱100　mg/kg组、ISO＋氧化苦参碱100　mg/kg组、ISO＋氧化苦参碱50　mg/kg组。各组大鼠预先灌胃给药（不同剂量氧化苦参碱或等体积生理盐水）7天后,ISO组、ISO＋氧化苦参碱（100　mg/kg、50　mg/kg）组大鼠灌胃给药同时皮下注射ISO（5　mg/kg）,正常对照组、氧化苦参碱100　mg/kg组皮下注射等体积生理盐水7天,共14天。随后检测各组大鼠心功能血流动力学参数、血清脑钠肽含量,观察心肌病理学表现,用Western　blot法对大鼠心肌cPLA2、COX-1、COX-2、PGIS进行半定量分析。结果　氧化苦参碱（100　mg/kg、50　mg/kg）能改善心力衰竭心脏收缩和舒张功能,显著降低ISO诱导的心力衰竭大鼠升高的血清脑钠肽水平;氧化苦参碱可显著减轻心力衰竭大鼠的心肌纤维化,并且显著升高ISO诱导的心力衰竭大鼠心肌组织中COX-2、PGIS的表达（P<0.01）,降低COX-1的表达（P<0.01）;氧化苦参碱对ISO诱导的慢性心力衰竭大鼠心肌组织中cPLA2的表达无明显影响。结论　氧化苦参碱可改善ISO诱导的心力衰竭大鼠的心脏功能及心肌纤维化,其机制可能与调节环氧合酶通路中COX-1、COX-2及PGIS的表达相关。     

食管癌组织环氧化酶-2的表达与血管生成的关系

目的:探讨环氧化酶-2(COX-2)在食管癌组织的表达及其与肿瘤血管生成的关系．方法:免疫组化法检测食管鳞癌手术切除标本90例和癌旁正常黏膜34例中COX-2表达,采用抗CD34抗体标记微血管内皮细胞,计算微血管密度(MVD)．分析COX-2表达与MVD及其与食管癌主要临床病理特征的相关性．结果:食管癌组织COX-2阳性表达率为84．4％显著高于癌旁正常黏膜的20．6％(x2=45．47,P =0．00)．COX-2表达与肿瘤细胞分化程度、临床TNM分期和淋巴结转移密切相关,TNM分期中Ⅲ Ⅳ期的食管鳞癌组织中COX-2表达率为92．9％,显著高于Ⅰ Ⅱ期的70．6％(x2= 7．99,P=0．005)．高、中分化的食管鳞癌组织中COX-2表达率为92．9％,显著高于低分化的 70．6％(x2=7．99,P=0．005)．伴有淋巴结转移的食管鳞癌组织中COX-2表达率为94．3％,显著高于无淋巴结转移的70．3％(x2=9．61,P= 0．002)．食管癌组织MVD值为29．68±3．81, 显著高于癌旁正常黏膜的15．12±2．80(t= 20．28,P=0．00)．MVD与肿瘤的TNM分期和淋巴结转移密切相关,TNM分期中Ⅲ Ⅳ期的食管鳞癌组织中MVD值为31．46±3．52,显著高于Ⅰ Ⅱ期的26．74±2．06(t=-7．09,P=0．00)．伴有淋巴结转移的食管鳞癌组织中MVD为 31．72±3．43,显著高于无淋巴结转移的26．76 ±2．01(f=-7．90,P=0．00)．Spearman等级相关分析表明,MVD与COX-2表达呈显著正相关(r =0．607．P=0．00)．结论:COX-2异常表达及其诱导的血管生成在食管癌的侵袭和淋巴结转移中起重要作用．     

Expression of cyclooxygenase-2 in colorectal cancer and its clinical significance

AIM: To clarify the clinicopathologic significance of COX-2 expression in human colorectal cancer. METHODS: A total of 128 surgically resected colorectal cancer specimens were immunohistochemically analyzed with the use of anti-COX-2, anti-VEGF and anti-MMP-2 antibodies. The relationship between the cyclooxygenase-2 expression in primary lesions of colorectal cancer and clinicopathoiogic parameters was evaluated by chi-square test. RESULTS: Among 128 cases of colorectal cancer, 87 (67.9%) were positive for cyclooxygenase-2. The expression of cyclooxygenase-2 was significantly correlated with the depth of invasion, stage of disease, and metastasis (lymph node and liver). Patients in T3-T4, stages Ⅲ-Ⅳand with metastasis had much higher expression of cyclooxygenase-2 than ones in T1-T2, stages Ⅰ-Ⅱ and without metastasis (P<0.05). Among 45 cases of colorectal cancer with lymph node metastasis, the COX-2-positive rate was 86.7% (39/45) for primary lesions and diffuse cytoplasmic staining for COX-2 protein was detected in cancer cells in 100% of metastatic lesions of the lymph nodes. VEGF expression was detected in 49 tumors (38.3%), and VEGF expression was closely correlated with COX-2 expression. The positive expression rate of VEGF (81.6%) in the cyclooxygenase-2-positive group was higher than that in the cyclooxygenase-2-negative group (18.4%, P<0.05). MMP-2 expression was detected in 88 tumors (68.8%), and MMP-2 expression was closely correlated with COX-2 expression. The positive expression rate of MMP-2 (79.6%) in the positive COX-2 group was higher than that in the negative COX-2 group (20.4%, P<0.05). CONCLUSION: Cyclooxygenase-2 may be associated with tumor progression by modulating the angiogenesis and cancer cell motility and invasive potential in colorectal cancer and it can be used as a possible biomarker.     

Cyclooxygenase-2 Overexpression Is Related to Polypoid Growth and K-<Emphasis Type="Italic">ras</Emphasis> Gene Mutation in T1 Colorectal Carcinomas

PURPOSE Cyclooxygenase-2 is thought to play a role in the development of intestinal tumors and levels are elevated in approximately 80 to 90 percent of human colorectal carcinomas. To clarify the role that cyclooxygenase-2 plays in the development of colorectal carcinoma, we studied the relationship between cyclooxygenase-2 expression and tumor morphology and that between cyclooxygenase-2 expression and K-ras mutation.METHODS We classified 48 T1 colorectal carcinomas as polypoid or nonpolypoid and analyzed the clinicopathologic features. The expression of cyclooxygenase-2 was determined immunohistochemically, and nested polymerase chain reaction-restriction fragment length polymorphism detected a K-ras codon 12 mutation.RESULTS Cyclooxygenase-2 expression was higher in polypoid carcinomas than in nonpolypoid carcinomas (P < 0.001). The K-ras codon 12 mutation was associated with higher levels of cyclooxygenase-2 expression compared with carcinomas without this mutation (P = 0.028).CONCLUSIONS Polypoid growth and K-ras gene mutation are both associated with increased levels of cyclooxygenase-2 expression in T1 tumors.Supported in part by grants from the Ministry of Education, Science, Sports, and Culture of Japan.     

前列腺素E2在环氧合酶-2促胰腺癌新生血管生成中的介导作用

目的 探讨环氧合酶-2(COX-2)促进胰腺癌新生血管生成过程中前列腺素E2(PGE2)的介导作用，进一步揭示COX-2促进胰腺癌生长的机制。方法 体外培养胰腺癌细胞株PC-3，分别应用酶联免疫吸附(ELISA)和放射免疫(RIA)等方法，检测选择性COX-2抑制剂Celebrex对胰腺癌PC3细胞血管内皮生长因子(VEGF)和PGR表达的调节作用，并观察外源性PGE2对Celebrex调节VEGF表达的干预。建立裸鼠PC3细胞移植瘤，Western印迹检测Celebrex对胰腺癌组织VEGF表达的影响，RIA测定Celebrex对胰腺癌组织PGB变化的调节。结果 随着Celebrex作用浓度的提高以及作用时间的延长，PC3细胞分泌的VEGF和PGE2受到抑制，呈时间和剂量依赖性。外源性PGE2显著上调Celebrex作用后PC-3细胞VEGF蛋白表达，呈剂量依赖性，体内实验表明，Celebrex可显著抑制移植瘤组织VEGF和PGE2的表达。结论 COX-2参与了PC-3细胞VEGF分泌的调节，进而促进胰腺癌新生血管形成，而PGE2则在该过程中起着重要的介导作用。     

Colorectal Adenomas and Diet

It has been postulated that high intakes of animal fat and protein and low intakes of fiber, calcium, and antioxidants increase the risk of colorectal cancer. Whether specific types of protein such as that from red meat are important, and whether vegetables might be key protective factors will also be considered in this study. Dietary intake over the past year was studied according to the diet history method by means of a case-control study in 184 cases and matched controls. After adjustment for energy, relative weight, and social class, no associations were found for fat or protein in comparison with either control group. Unexpectedly, carbohydrate intake was inversely related with adenoma risk, the RR being 0.29 (0.10-0.81) for quintile 5 versus 1 in comparison with hospital controls. None of the antioxidants showed a significant protective effect except beta-carotene intake in comparison with hospital controls, the RR being 0.24 (0.11-0.50) for the highest versus the lowest quintile. There was, however, a statistically significant positive association between adenomas and meat consumption with the RR for the highest versus the lowest quintile. There was, however, a statistically significant positive association between adenomas and meat consumption with the RR for the highest versus the lowest quintile of intake being 3.6 (1.7-7.5) in comparison with hospital controls and 4.4 (1.6-12.1) in comparison with population controls. Our data support the protective role for carbohydrate intake and of beta-carotene intake in the etiology of colorectal adenomas and show a strong increased risk for developing adenomas in those with high meat intake.     

15-PGDH在大肠腺癌中的表达

目的研究NAD+依赖性15-羟基前列腺素脱氢酶(15-PGDH)在大肠腺癌组织、大肠腺瘤组织及正常大肠组织中的表达,探讨15-PGDH在大肠腺癌组织中的表达情况及其与大肠腺癌临床病理因素的关系。方法应用免疫组织化学(SABC)法检测40例大肠腺癌组织、20例大肠腺瘤组织和20例正常大肠组织中15-PGDH的表达情况。结果15-PGDH在大肠腺癌(15%)和腺瘤组织(20%)中的阳性表达率显著低于在正常大肠组织(100%)中的阳性表达率(P0.01),而15-PGDH在大肠腺癌和腺瘤中的表达无统计学差异(P0.05)。15-PGDH蛋白表达情况与大肠腺癌患者的性别、年龄、分化程度及Dukes分期和有无淋巴结转移等临床病理参数均无关系(P0.05)。结论大肠腺癌组织中15-PGDH表达减少或缺失,且其表达与大肠腺癌的分期分化等病理参数并无关系。15-PGDH的表达缺失或减少可能发生在大肠腺癌发生发展的早期,是大肠腺癌发生的抑制物。