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 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.     

Leptin and peroxisome proliferator-activated receptor γ expression in colorectal adenoma

AIM: To investigate the expressions of leptin and peroxisome proliferator-activated receptor γ (PPARG) in relation to body mass index (BMI).METHODS: We evaluated leptin and PPARG expression in 30 adenomas over 1 cm in size by immunohistochemical staining. In addition, clinicopathologic features including BMI were assessed.RESULTS: PPARG and leptin expression showed a strong positive correlation (P = 0.035). The average BMI of the leptin-positive group was higher than that of the leptin-negative group (25.4 ± 3.4 kg/m² vs 22.6 ± 2.4 kg/m², P = 0.018), and leptin expression was significantly correlated with high BMI (P = 0.024). Leptin expression was more frequently observed in intermediate/high grade dysplasia than in low grade dysplasia (P = 0.030). However, PPARG expression was not correlated with BMI and grade of dysplasia.CONCLUSION: BMI has influenced on the leptin expression of colorectal adenoma. The exact mechanism underlies the strong correlation between leptin and PPARG expression needs further study.     

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.     

The expression of CD66a and possible roles in colorectal adenoma and adenocarcinoma

Background The aim of our study was to analyze the expression and possible role of CD66a in colorectal adenoma and adenocarcinoma and the relationship between its expression and pre-operation serum carcinoembryonic antigen (CEA) level and tumor stage in patients with colorectal adenocarcinomas. Methods Paraffin-embedded sections from 184 patients including 42 colorectal adenomas with low-grade dysplasia, 43 adenomas with high-grade dysplasia, and 99 adenocarcinomas were collected for this study. Immunohistochemical analysis was performed, and the expression and the location of CD66a were evaluated and were correlated with β-catenin nuclear expression. Results The expression of CD66a was found not only in the apical membrane of neoplastic glands but also in secretion within the lumen of the neoplastic glands including adenomas and adenocarcinomas. Expressions of secreted CD66a were of higher level in adenocarcinoma than in adenoma with high-grade dysplasia and adenoma with low-grade dysplasia (p < 0.0001). High expression of secreted CD66a was also associated with tumor stage, invasion, and pre-operation serum CEA level of patients with colorectal adenocarcinoma. Conclusions This study implied that CD66a can function both as an epithelial cell adhesion protein or alternatively as secreted CD66a. In addition, a high expression of CD66a was significantly correlated with tumor invasion, stage, and pre-operation serum CEA level.     

AMACR is associated with advanced pathologic risk factors in sporadic colorectal adenomas

AIM: To analyze α-methylacyl CoA racemase (AMACR) expression in relation to various dysplasia phenotypes and clinicopathological parameters of sporadic colorectal adenomas.METHODS: Fifty-f ive cases of sporadic colorectal adenomas were categorized according to the Vienna classif ication for Gastrointestinal Neoplasia.These corresponded to a total of 98 different intra-lesion microscopic f ields that were further independently assigned a histological grade based on the old nomenclature (mild,moderate,severe ...     

Immunoreactive Transforming Growth Factor β-1, Its Receptor,bcl-2 Protein,and p53 Protein in Colorectal Adenomas

Abstract: Immunoreactive transforming growth factor-β1 (TGF-β1), its receptor (TGFR), bcl-2 protein, and p53 protein were stained in 47 samples of normal colonic mucosa and 33 samples of colorectal adenoma, with the aim of exploring an alternate, novel pathway of colorectal tumorigenesis. There was no difference in the percentage of cells positive for TGF-β1 immunoreactivity between normal mucosae and adenomas. TGFR immunoreactivity was detected in a significantly higher percentage of normal mucosae than of adenomas (p ±0.05). Bcl-2 protein and p53 protein immunoreactivities were detected in a significantly higher percentage of adenomas than of normal mucosae (p ±0.01). Expression of these immunoreactive proteins did not correlate with any of the clinicopathological features of adenomas, except for a significant negative correlation between TGFR expression and large tumor size (p±0.05) and a positive correlation between p53 protein expression and the grade of dysplasia (p±0.05). These findings indicate that (1) TGF-β1 plays little role in the tumorigenesis of colorectal adenomas, (2) TGFR is lost in most adenomas during tumorigenesis, (3) bcl-2 protein plays an important role in transformation of normal mucosa into adenoma, and (4) p53 protein is involved in the very early phase of malignant transformation from adenoma to carcinoma.     

The Immunohistochemical expression of endothelial cell differentiation gene-2 receptor in human colorectal adenomas

BACKGROUND/AIMS: The EDG-2 (endothelial cell differentiation gene-2) has been characterized as one of the high-affinity receptors of lysophosphatidic acid: an extracellular lipid mediator which can induce tumor progression. Recent studies have revealed that EDG-2 plays an important role in various pathological events including cell proliferation and tumor development. The investigation of EDG-2 is thus considered important for eliciting the mechanism of tumorigenesis. However, in colorectal tissue, the clinical significance of EDG-2 expression remains unclear. In the current study, we examined the immunohistochemical expression of EDG-2 in colorectal mucosa and adenoma, and clarified its relation with the clinicopathological features. METHODOLOGY: One hundred and sixty-one colorectal polyps were resected endoscopically or surgically at our institute from 2000 to 2001. According to the degree of dysplasia, adenomas were grouped into two categories: low-grade (mild or moderate dysplasia) and high-grade (severe dysplasia or carcinoma in situ). We investigated EDG-2 expression by immunohistochemistry. RESULTS: EDG-2 was expressed almost exclusively in the cytoplasm in colorectal normal mucosa and adenoma. EDG-2 expression in normal mucosa and adenoma was 8% and 76%, respectively. EDG-2 expression was increased in low-grade adenoma compared with that in normal mucosa (P < 0.001). EDG-2 expression was significantly greater in adenomas with larger diameters (P < 0.001). CONCLUSIONS: We demonstrated that EDG-2 expression was increased in the early stage of adenoma. A significant correlation between EDG-2 expression and the size of the adenomas suggests that EDG-2 may play an important role in the growth of these adenomas.     

CD44 expression in benign and malignant colorectal polyps

PURPOSE: This retrospective study was undertaken to evaluate immunohistochemically the expression of CD44 standard protein and CD44v5 and CD44v6 isoforms in colorectal adenomas and early invasive cancers developing within adenomas as possible markers characterizing colorectal polyps with a more aggressive biologic potential. METHODS: Archival tissues of 81 consecutive locally resected colorectal polyps, comprising 57 colorectal adenomas and 24 carcinomas-in-adenomas, were stained immunohistochemically with the use of commercially available mouse monoclonal antibodies: SFF-2 for CD44 standard protein, VFF-8 for CD44v5, and VFF-7 for CD44v6. RESULTS: Sixtythree percent of the colorectal polyps were positive for CD44 standard protein, 59 percent were positive for CD44v5, and 27 percent were positive for CD44v6. Ninetythree percent of the low-grade adenomas were CD44 standard protein-positive, in contrast to 50 percent of the high-grade adenomas and only 42 percent of the carcinomas-in-adenomas (Kendall's Tau =–0.42;P<0.0001). CD44v6 expression was more frequently found in early invasive cancers (54 percent) than in high-grade adenomas (25 percent) and low-grade adenomas (7 percent). This difference also was statistically significant (Kendall's Tau-b =0.39;P=0.00003). Surprisingly, a downregulation of CD44 standard protein expression was observed in the adenoma tissue adjacent to carcinomas (62 percent) and areas with high-grade atypia (71 percent), compared with low-grade adenomas (93 percent; Kendall's Tau-b =–0.28;P=0.004). CONCLUSIONS: Our data suggest that CD44 standard protein and CD44 isoform v6 expression differs considerably in benign and malignant colorectal polyps. Clinical studies with larger patient groups could clarify the prognostic potential of CD44 further     

Cyclooxygenase-2 expression according to size and location of gastric and colorectal tubular adenomas]

BACKGROUND/AIMS: Recent studies have shown that cyclooxygenase-2 (COX-2) may be involved in the process of invasion, growth and apoptosis in colorectal carcinoma and in the growth and tumorigenesis in familial adenomatous polyposis. This study was conducted to determine the significance of the expression of COX-2 in gastric and colorectal adenomas. METHODS: Forty-nine samples of gastric adenoma and fifty-seven samples of colorectal adenoma were obtained by endoscopic mucosal resection or polypectomy from 106 patients from January 2000 to July 2003. COX-2 expression was determined by immunohistochemistry. Correlation between COX-2 expression and several clinical factors were compared in each gastric and colorectal adenomas. RESULTS: The expression of COX-2 in epithelial cells was significantly higher in the group with large adenoma (>1 cm) compared with the group with small adenoma (< or =1 cm) in gastric (76.5% vs. 46.7%, p=0.04) and colorectal adenomas (75% vs. 41.5%, p=0.023). Moreover, increased COX-2 expression was shown in distal compared to proximal colorectal adenoma (64.3% vs. 37.9%, p=0.047). CONCLUSIONS: COX-2 was expressed in a size-dependent manner in gastric and colorectal tubular adenomas. The expression of COX-2 was different according to the location of colorectal adenoma. The association of COX-2 expression with the size of adenoma may suggest that the role of COX-2 is not related to the early development of adenoma, but related to the progression of adenoma.     

Characteristics of and risk factors for colorectal neoplasms in young adults in a screening population

AIM: To investigate prevalence and risk factors for colorectal neoplasms in adults aged 50 years, for whom screening is not recommended.METHODS: This cross-sectional study compared prevalence and characteristics of colorectal and advanced adenomas in patients aged 50 years who underwent colonoscopy screening with subjects aged ≥ 50 years. To evaluate risk factors for colorectal and advanced adenoma in young adults, we used multivariable logistic regression models. Colorectal neoplasm characteristics were evaluated and compared with those in older patients.RESULTS: Among 2819 patients included, prevalences of colorectal adenoma and advanced adenoma were 19.7% and 1.5%, respectively. As patient age increased, so did the prevalence of colorectal neoplasm. However, prevalence of advanced adenoma did not differ between age-groups 45-49 years and ≥ 50 years(OR = 0.43, 95%CI: 0.17-1.07, P = 0.070). In younger age-group( 50 years), colorectal adenoma was significantly associated with older age, waist circumference(OR = 1.72, 95%CI: 1.15-2.55, P = 0.008), and current smoking(OR = 1.60, 95%CI: 1.07-2.41, P = 0.023). Alcohol consumption was an independent risk factor for colorectal advanced adenoma(OR = 3.69, 95%CI: 1.08-12.54, P = 0.037). Multiple neoplasms and large neoplasms(≥ 1 cm) were more prevalent in subjects ≥ 50 years.CONCLUSION: Current screening strategies for colorectal cancer may need to be amended to account for patient age, especially in young subjects with abdominal obesity, current smoking and alcohol consumption.     

Cyclooxygenase-2 is overexpressed in serrated adenoma of the colorectum

PURPOSE: The aim of this study was to clarify whether cyclooxygenase-2 and cyclooxygenase-1 is expressed in hyperplastic polyps and serrated adenomas. METHODS: Forty-nine serrated adenomas and 25 hyperplastic polyps were immunostained using anticyclooxygenase-2 and anticyclooxygenase-1 antibodies. Cyclooxygenase-2 and cyclooxygenase-1 expression was investigated in all specimens. RESULTS: Cyclooxygenase-2 was expressed in dysplastic glands in the majority of serrated adenomas. Thirty-five of 49 (71.4 percent) serrated adenomas exhibited moderate to intense cyclooxygenase-2 immunoreactivity, and 8 of 25 hyperplastic polyps (32 percent) showed weak to moderate cyclooxygenase-2 immunoreactivity. Cyclooxygenase-1 immunoreactivity was very weak in all the hyperplastic polyps and serrated adenomas. CONCLUSIONS: These results suggest that cyclooxygenase-2 is overexpressed in serrated adenoma of the colorectum. Cyclooxygenase-2 inhibitors will reduce the incidence of serrated adenomas.     

Proximal adenomas in hereditary non-polyposis colorectal cancer are prone to rapid malignant transformation

BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is thought to arise from adenomas. HNPCC mostly occurs in the proximal colon. We investigated whether this proximal preponderance is due to a proximal preponderance of adenomas or (also) differences in transformation rates from adenomas to cancer between the distal and proximal colon. METHODS: A total of 100 HNPCC adenomas were evaluated and compared with 152 sporadic adenomas for location, size, and dysplasia. Twenty five adenomas from patients with a known mismatch repair (MMR) gene mutation were stained for expression of MLH1 and MSH2. RESULTS: HNPCC adenomas were more often located proximally (50% v 26%; p=0.018) and were smaller in comparison with sporadic adenomas. They were similarly dysplastic. However, all proximal HNPCC adenomas > or =5 mm were highly dysplastic compared with 17% of the larger proximal sporadic polyps (p<0.001). They were also more often highly dysplastic than larger distal HNPCC adenomas (p<0.001). Small HNPCC adenomas were, except for their location, not different from sporadic adenomas. Fifteen of the 25 "known mutation" adenomas showed loss of expression of either MLH1 or MSH2. The 10 adenomas with expression were all small with low grade dysplasia. CONCLUSION: HNPCC adenomas are located mainly in the proximal colon. The progression to high grade dysplasia is more common in proximal than distal HNPCC adenomas, indicating a faster transformation rate from early adenoma to cancer in the proximal colon. MMR gene malfunction probably does not initiate adenoma development but is present at a very early stage of tumorigenesis and heralds the development of high grade dysplasia.     

Incidence of colorectal neoplasms among male pilots

AIM: To assess the prevalence of colorectal neoplasms (adenomas, advanced adenomas and colorectal cancers) among Israeli military and commercial airline pilots.METHODS: Initial screening colonoscopy was performed on average-risk (no symptoms and no family history) airline pilots at the Integrated Cancer Prevention Center (ICPC) in the Tel-Aviv Medical Center. Visualized polyps were excised and sent for pathological examination. Advanced adenoma was defined as a lesion >10 mm in diameter, with high-grade dysplasia or villous histology. The results were compared with those of an age- and gender-matched random sample of healthy adults undergoing routine screening at the ICPC.RESULTS: There were 270 pilots (mean age 55.2 ± 7.4 years) and 1150 controls (mean age 55.7 ± 7.8 years). The prevalence of colorectal neoplasms was 15.9% among the pilots and 20.6% among the controls (P = 0.097, χ² test). There were significantly more hyperplastic polyps among pilots (15.5% vs 9.4%, P = 0.004) and a trend towards fewer adenomas (14.8% vs 20.3% P = 0.06). The prevalence of advanced lesions among pilots and control groups was 5.9% and 4.7%, respectively (P = 0.49), and the prevalence of cancer was 0.7% and 0.69%, respectively (P = 0.93).CONCLUSION: There tends to be a lower colorectal adenoma, advanced adenoma and cancer prevalence but a higher hyperplastic polyp prevalence among pilots than the general population.     

Association between colorectal adenoma and coronary atherosclerosis detected by CT coronary angiography in Korean men; a cross-sectional study

Background: Colorectal adenoma and coronary artery disease (CAD) appear to share common risk factors, such as male gender, diabetes mellitus, smoking, and obesity. We investigated the relationship between colorectal adenoma and coronary atherosclerosis, as a risk factor for colorectal adenoma. Methods: A cross‐sectional study was conducted on Korean men who presented for a health check‐up. The subjects were 488 men (217 colorectal adenoma and 271 normal colonoscopic findings) who underwent colonoscopy and coronary computed tomography angiography (CTA) on the same day as a screening examination. Advanced colonic lesion was defined as a presence of adenoma with villous component, high‐grade dysplasia, and/or with size of ≥1 cm. CTA findings were classified as normal, mild (low‐grade atherosclerosis or <50% stenosis), and significant CAD (≥50% stenosis). Abnormal CTA findings included mild and significant CAD. Results: Patients with abnormal CTA findings were more likely to have colorectal adenoma compared with those with normal CTA findings (P < 0.005). Furthermore, presence of advanced adenoma was significantly associated with significant CAD (P < 0.01). On multivariate analyses, abnormal CTA findings (OR = 1.66, 95% CI: 1.14–2.41, P < 0.01) and significant CAD (OR = 1.96, 95% CI: 1.15–3.35, P < 0.05) were found to be independent risk factors for colorectal adenoma after adjusting for age, current smoking, and metabolic syndrome. Conclusions: In this study, in the population who underwent CTA and colonoscopy for health check‐up, prevalence of colorectal adenoma was greater in subjects with low‐grade coronary atherosclerosis or significant CAD. The presence of advanced adenoma was significantly associated with significant CAD.     

Increased tumor necrosis factor receptor 1 expression in human colorectal adenomas

AIM: To determine the expression statuses of tumor necrosis factor (TNF)-α, its receptors (TNF-R) and downstream effector molecules in human colorectal adenomas. METHODS: We measured the serum concentrations of TNF-α and its receptors in 62 colorectal adenoma patients and 34 healthy controls. The protein expression of TNF-α, TNF-R1, TNF-R2 and downstream signals of the TNF receptors, such as c-Jun N-terminal kinase (JNK), nuclear factor-κ B and caspase-3, were also investigated in human colorectal adenomas and in normal colorectal mucosal tissues by immunohistochemistry. Immunofluorescence confocal microscopy was used to investigate the consistency of expression of TNF-R1 and phospho-JNK (p-JNK). RESULTS: The serum levels of soluble TNF-R1 (sTNF-R1) in adenoma patients were significantly higher than in the control group (3.67 ± 0.86 ng/mL vs 1.57 ± 0.72 ng/mL, P 0.001). Receiver operating characteristic analysis revealed the high diagnostic sensitivity of TNF-R1 measurements (AUC was 0.928) for the diagnosis of adenoma, and the best cut-off level of TNF-R1 was 2.08 ng/mL, with a sensitivity of 93.4% and a specificity of 82.4%. There were no significant differences in the serum levels of TNF-α or sTNF-R2 between the two groups. Immunohistochemistry showed high levels of TNF-R1 and p-JNK expression in the epithelial cells of adenomas. Furthermore, a high incidence of co-localization of TNF-R1 and p-JNK was identified in adenoma tissue. CONCLUSION: TNF-R1 may be a promising biomarker of colorectal adenoma, and it may also play an important role in the very early stages of colorectal carcinogenesis.     

Immunohistochemical Expression of PCNA and CD34 in Colorectal Adenomas and Carcinomas Using Specified Automated Cellular Image Analysis System: A Clinicopathologic Study

Background/Aim:

To evaluate the immunohistochemical expression of proliferating cell nuclear antigen (PCNA) and CD34 in colorectal adenomas and carcinomas, and to correlate this expression with different clinicopathologic parameters.

Materials and Methods:

The study was retrospectively designed. A total of 86 tissue samples, including 33 paraffin blocks from patients with colorectal adenomas, 33 paraffin blocks from patients with colorectal adenocarcinomas, and a control group of 20 samples of nontumerous colonic tissue, were included in the study. From each block, 3 sections of 5 ΅m thickness were taken, 1 section was stained with hematoxylin and eosin (H and E) and the other 2 sections were stained immunohistochemically for PCNA and CD34. Scoring of the immunohistochemical staining was performed using a specified automated cellular image analysis system (Digimizer).

Results:

PCNA expression was significantly increased in a sequence of normal mucosa–adenoma–carcinoma. It was significantly higher in adenomas ≥ 1 cm and those with severe dysplasia, and it showed a significant positive correlation with grade and lymph node involvement in colorectal carcinoma. CD34 showed significantly higher expression in carcinoma than adenoma and in adenoma than in the control group. CD34 expression showed a significant correlation with adenomas carrying severe dysplasia and large-sized adenomas (≥1cm). It was significantly correlated with tumor grade, lymphovascular invasion, and lymph node involvement in colorectal carcinoma.

Conclusion:

PCNA plays an important role in colorectal neoplastic progression and can be utilized as ancillary marker for the risk of malignant transformation in colorectal adenomas as it correlates with high grade dysplasia and size. Intratumoral quantification of the mean (A and N) of CD34 in colorectal carcinoma reflects the grade of tumors and can predict lymph node involvement and lymphovascular invasion, to make a useful additional prognostic factor.     

Helicobacter pylori infection concomitant with metabolic syndrome further increase risk of colorectal adenomas

AIM: To investigate the association of colorectal adenomas with both Helicobacter pylori (H. pylori) infection and metabolic syndrome. METHODS: Using a cross-sectional hospital-based study, we analyzed physical examination data from 9311 healthy subjects with overnight physical examinations performed between January 2004 and December 2006. Examined data included gender, age, life style, anthropometric measurements, blood pressure, biochemical and hematological studies, H. pylori infection detected by esophagogastroduodenoscopy and biopsy urease tests, and colorectal adenomas detected with a complete total colonoscopy. RESULTS: The prevalence values for H. pylori infection, metabolic syndrome, and colorectal adenoma were39.2%, 18.7%, and 20.7%, respectively. Colorectal adenoma risk factors included male gender [odd ratio (OR): 2.005, 95% conf idence interval (CI): 1.740-2.310, P < 0.001], advanced age (OR: 1.046, 95% CI: 1.040-1.052, P < 0.001), smoking (OR: 1.377, 95% CI: 1.146-1.654, P = 0.001), increased body fat (OR: 1.016, 95% CI: 1.007-1.026, P = 0.001), higher white blood cell count (OR: 1.038, 95% CI: 1.005-1.073, P = 0.025), H. pylori infection (OR: 1.366, 95% CI: 1.230-1.517, P < 0.001), and metabolic syndrome (OR: 1.408, 95% CI: 1.231-1.610, P < 0.001). In addition, concomitant H. pylori infection with metabolic syndrome further increased the probability of colorectal adenomas. CONCLUSION: Our study revealed H. pylori infection with concomitant metabolic syndrome might further increase the risk of colorectal adenomas.     

Potential Role of Apoptosis and Apoptotic Regulatory Proteins in Colorectal Neoplasia: Correlations with Clinico-Pathological Parameters and Survival

An imbalance between apoptotic and proliferative processes is believed to underlie colorectal neoplasia. We evaluated the expression of bcl-2, p53, mdm2 proteins, and apoptosis in colorectal neoplasms, as well as their correlation with clinico-pathological parameters, using image analysis. Biopsies from 46 colorectal cancers, 121 adenomas, and 25 controls were studied using monoclonal antibodies against p53, bcl-2, mdm2 and the terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL) method for apoptosis. P53 and bcl2 protein expression was higher in adenomas ≥1 cm (P < 0.03) and tubulovillous-villous adenomas (P < 0.03), and correlated with dysplasia (P < 0.03). In Cox regression analysis, Dukes’ stage was the most significant independent prognostic indicator of a worse survival (P < 0.019), whereas when stage was eliminated, bcl-2 expression was also a powerful predictor for bad prognosis (P = 0.02). In conclusion, both bcl-2 and p53 immunohistochemical profiles may be useful adjuncts in detecting adenomas with a malignant potential, whereas bcl-2 could be used in combination with Dukes’ stage as a predictor of prognosis in colorectal cancer.