Expression of the Cancer Stem Cell Markers CD44 and CD133 in Colorectal Cancer: An Immunohistochemical Staining Analysis

PURPOSE: The aim of this study was to assess the expressions of CD44 and CD133 in colorectal cancer tissue by using immunohistochemical staining and to analyze the clinical significance of the expressions related to other clinicopathological data and survival results. METHODS: One hundred sixty-two patients with a biopsy-proven colorectal adenocarcinoma who were operated on between January 1998 and August 2004 were enrolled in this study. Immunohistochemical staining for CD44 and CD133 was performed on primary colorectal cancer tissue, metastatic lymph nodes, and synchronous and metachronous metastatic tumor tissues if available. RESULTS: CD44 expression was stronger in the primary tumor than in metastatic lymph nodes (P < 0.001), and CD133 expression tended to be stronger in primary tumor than in metastatic lymph nodes (P = 0.057). No significant correlation was found between the CD44 and the CD133 expressions. The cases with recurrence showed low expression of CD44 (P = 0.017). CD133 expression was lower in cases with elevated CA 19-9 serum levels (P = 0.028) and advanced T stage (P = 0.038). Multivariate analysis proved that low expression of CD44 was an independent prognosis factor for short disease-free survival (P = 0.028). CONCLUSION: Low CD44 expression was correlated with increased tumor recurrence and short disease-free survival, and low CD133 expression was associated with advanced tumor stage. We suggest that further studies be performed to evaluate whether the immunohistochemical method for determining the CD44 and the CD133 expressions is appropriate for exploring cancer stem-cell biology in patients with colorectal cancer.

Inflammation-based score (Glasgow prognostic score) as an independent prognostic factor in colorectal cancer patients

PURPOSE: This study was conducted to evaluate the systemic inflammatory response in colorectal cancer patients, and to estimate the usefulness of the Glasgow prognostic score (GPS) as a prognostic factor. METHODS: Patients with biopsy-proven colorectal adenocarcinoma who were operated between April 2005 and December 2008 were enrolled in this study. The GPS was estimated based on the measurement of CRP and serum albumin level. The GPS was compared with other clinicopathological factors. Univariate and multivariate analyses were performed to evaluate the factors affecting cancer-specific survival. RESULTS: GPS was significantly higher in patients with anemia, thrombocytosis, a high neutrophil to lymphocyte ratio, tumor of the colon, and large tumor. Patient age, gender, serum CEA level, tumor gross appearance, TNM stage, and tumor differentiation were not related with the GPS. In univariate analysis, hemoglobin, CEA, gross appearance of tumor, TNM stage, tumor differentiation, and GPS were associated with cancer-specific survival. In multivariate analysis, TNM stage (III or IV : I or II; hazard ratio [HR], 12.322; P = 0.015), tumor differentiation (poorly differentiated : well or moderately differentiated; HR, 3.112; P = 0.021), and GPS (GPS 2 : GPS 0 or 1; HR, 5.168; P = 0.003) were identified as independent prognostic factors in colorectal cancer. CONCLUSION: Our study showed that the GPS was an independent variable from tumor stage and a good and convenient prognostic factor in colorectal cancer patients.

Matrix Metalloproteinase-2 and -7 Expression in Colorectal Cancer

PURPOSE: Matrix metalloproteinase-2 (MMP-2) and MMP-7 have been implicated in tumor growth and metastasis. This study aimed to investigate the expressions of MMP-2 and -7 in colorectal cancer and to evaluate their values as prognostic markers. METHODS: Immunohistochemical staining for MMP-2 and -7 was done in 144 resected colorectal cancer specimens. Clinicopathological data and survival results were compared with regard to the expression results. RESULTS: The expression rates of MMP-2 in tumor cells in the tumor center and the tumor border were 16.7% and 38.9%, respectively. That of MMP-2 in stromal cells was 27.8%. MMP-7 immunoreactivities of tumor cells in the tumor center and the tumor border were 6.9% and 23.6%. The expressions of MMP-2 and MMP-7 were correlated. MMP-2 expression in stromal cells was more increased in the distal part of the colorectum: 8.8% in right colon cancer, 29.5% in left colon cancer and 36.4% in rectal cancer. MMP-2 expression of tumor cells in the tumor border was correlated with T-stage. MMP-7 expression of tumor cells in the tumor border was increased in case of infiltrative cancer compared with fungating tumor. The expression patterns of MMP-2 and -7 were not correlated with other clinicopathological factors, including tumor markers, node metastasis, distant metastasis, lymphatic invasion, tumor differentiation, and recurrence. No significant associations between the overall and disease-free survival rates and the MMP-2 and -7 expression patterns were noted. CONCLUSION: The high expression rates of MMP-2 and -7 in tumor borders suggest that MMP-2 and -7 have some role in tumor invasion, but in this study, MMP-2 and -7 did not appear to be significant predictors of prognosis in colorectal cancer.

Clinical Importance of Vimentin and MMP 2 Expression in Hepatocellular Carcinoma

BACKGROUND / PURPOSE: Hepatocellular carcinoma (HCC) is a common cancer with a poor prognosis. A better understanding of the molecular mechanisms underlying the genesis of HCC, as well as the progression of HCC, allow for improved prediction of the prognosis of patients with HCC and more effective treatment. In this study, we determined the expression of vimentin and matrix metalloproteinase 2 (MMP 2) and evaluated the clinical significance in (HCC). METHODS: Immunohistochemical staining was performed for vimentin and MMP 2 in 98 surgically resected HCC specimens using the tissue microarray method. The clinicopathologic data and the outcomes were reviewed, and the levels of expression of vimentin and MMP 2 were compared. RESULTS: Positive expression of vimentin and MMP 2 was observed in 7.1% and 41.8% of specimens, respectively. The overexpression of vimentin and MMP 2 had a positive correlation with tumor cell proliferative activity, as measured by the Ki-67 labeling index (p<0.001 and p=0.043, respectively), but was not correlated with the TUNEL labeling index. Other clinicopathological factors, such as platelet count, serosal invasion, Edomondson grade, capsule infiltration, TNM stage(UICC, 6th edition) and extrahepatic metastases in patients with recurrences had a significant correlation with vimentin. The presence of portal vein thrombosis approached statistical significance with MMP 2 expression. In the survival analysis, overexpression of vimentin and MMP 2 was correlated with a poor overall survival rate based on univariate analysis (p=0.002 and, p=0.047, respectively), but not based on multivariate analysis. CONCLUSION: In HCC, vimentin and MMP 2 may have a role in cancer progression with more aggressive potential, thus suggesting their use as a prognostic markers in HCC.

Occult Papillary Thyroid Carcinoma Presenting as a Cystic Neck Mass / 대한내분비외과학회지

The majority of cystic masses in the lateral neck are benign entities, and these entities include branchial cyst. Occult papillary thyroid carcinoma can occasionally present with regional lymph node metastasis. However, cystic metastasis from occult papillary thyroid carcinoma is a very rare condition. We present here a case of a cystic neck mass as the sole initial clinical manifestation of metastatic occult papillary thyroid carcionoma.

Prognostic Value of Erythrocyte Sedimentation Rate in Patients with Colorectal Cancer

PURPOSE: Prognostic indicators are used increasingly in clinical trials and to guide surveillance for patients with colorectal cancer (CRC). The significance of a preoperative, elevated erythrocyte sedimentation rate (ESR) as a predictive indicator for malignancy and for prognosis in colorectal cancer has not been elucidated. Hence, the current study was conducted to evaluate the ESR as a prognostic indicator in patients with CRC. METHODS: This study enrolled 232 patients who underwent surgery in our hospital between 1997 and 2004. ESR with clinicopathologic features and overall survival were evaluated retrospectively. RESULTS: The ESRs of 139 patients were elevated, and those of 93 patients were normal. Elevated ESR was associated with the male gender, decreased hemoglobin, increased platelet count, high preoperative CEA, high preoperative CA19-9, tumor size (> or =5 cm), T stage, and TNM stage. Patients with elevated ESR had poorer survival (P=0.001), but a multivariate analysis did not reveal an elevated ESR as an independent factor for prognosis. CONCLUSIONS: Preoperative elevation of ESR in patients with CRC suggests the presence of a tumor with aggressive behavior and a poor outcome.

The Prognostic Value of CA19-9 in Patients with Colorectal Cancer

PURPOSE: There has been much debate about the significance of the CA19-9 level for predicting the prognosis of colorectal cancer patients. This study aimed to evaluate the prognostic value of the preoperative serum CA19-9 level and the CA19-9 expression in the tumor tissues of colorectal cancer patients METHODS: One hundred patients with colorectal cancer and who had been treated by resection were studied. We assessed the correlations of the preoperative serum CA19-9 level and the status of the CA19-9 immunohistochemical staining with the clinicopathologic features, including the prognosis of the patients. RESULTS: The preoperative serum CA19-9 level had significant correlation with the status of CA19-9 immunohistochemical staining. The presence of distant metastasis was significantly correlated with an elevated level of serum CA19-9. The depth of tumor, the presence of lymph node metastasis, the TNM stage and tumor cell differentiation were significantly correlated with the status of the CA19-9 immunohistochemical staining. In addition, the gross morphology, depth of tumor, the presence of lymph node metastasis, the TNM stage, the status of the CA19-9 immunohistochemical staining and the serum CEA level were correlated with survival on univariate analysis. However, multivariate analysis did not validate the status of CA19-9 immunohistochemical staining as a significantly independent predictor of the prognosis. CONCLUSION: The CA19-9 expression was frequently observed in advanced stage tumor tissue, yet its expression in tumor tissue or the preoperative CA19-9 serum level did not show independent prognostic value for colorectal cancer patients.

Clinical Significance of Thrombocytosis in Patients with Colorectal Cancer

PURPOSE: Thrombocytosis is commonly associated with various tumors, including stomach, ovarian, lung, liver and pancreas cancers. Some clinical reports have shown thrombocytosis to be associated with the disease stage and prognosis. This study investigated the prevalence of the thromobocytosis in patients with colorectal cancer, and its association with the prognosis. METHODS: Two hundreds ninety-six patients with colorectal cancer who had been surgically treated at our hospital between 1997 and 2004 were enrolled in this study. The incidence, relationship with other clinicopathological factors, and the prognostic value of thrombocytosis were evaluated retrospectively. RESULTS: Thirty-seven of the 290 (12.8%) patients had thrombocytosis. The incidence of thrombocytosis was examined with regard to gender (P=0.018), tumor location (P=0.021), and T stage of tumor (P or =5 ng/ml) to be associated with both the disease-free survival (DFS) and overall survival (OS). Multivariate analysis revealed thrombocytosis to be significantly associated with the disease-free survival (P=0.026). CONCLUSION: Preoperative thrombocytosis appears to be an independent prognostic indicator of the DFS in patients with colorectal cancer.

Prognostic Value of Preoperative Serum Levels of CEA and CA19-9 in Patients with Colorectal Cancer

PURPOSE: The significance of serum levels of CEA and CA19-9 in forming a prognosis for colorectal cancer patients remains as subject for debating. The aim of this study is to assess their correlations with tumor pathology and their prognostic values. METHODS: We analysed the data on 274 patients with colorectal cancer who had been treated by resection from Jan. 1997 to Aug. 2005. Correlation of the preoperative serum values of CEA and CA19-9 with clinocopathologic features, including prognosis, of the patients was investigated. RESULTS: The positivity rates of the two tumor markes were significantly correlated with tumor size, differentiation, TNM staging, venous invasion, and neural invasion. In addition, the positivity rate of CEA was related to lymphatic invasion and that of CA19-9 to gender. In the univariate analysis, CEA (P<0.001), CA19-9 (P<0.001), tumor size (P=0.011), TNM staging (P<0.001), lymphatic invasion (P=0.003), venous invasion (P<0.001), neural invasion (P<0.001), and differentiation (P=0.023) correlated with survival of the patients. In the stepwise multivariate analysis, an advanced TNM stage (P<0.001), positive venous invasion (P=0.011), and positive neural invasion (P=0.013) were independent prognostic factors for poor survival. CONCLUSIONS: Our results demonstrated that high serum levels of tumor markers were associated with more aggressive cancers, but in the multivariate analysis, CEA and CA19-9 were found not to be independent prognostic factors.

Study of CpG Methylation of the p16 and MGMT Promoter in Hepatocellular Carcinoma

PURPOSE: The aims of this study were to examine the methylation status of the p16 and MGMT promoters in hepatocellular carcinoma (HCC), and to evaluate the relationship between the loss of gene expression, the promoter methylation status and hepatocarcinogenesis. METHODS: We included 24 HCC tissues and their adjacent non-tumorous tissues and 5 normal liver tissues in our study, and all the specimens were obtained by hepatectomy. The methylation status of the p16 and MGMT promoter regions were evaluated by methylation-specific polymerase chain reaction (MSP) and quantitative analysis by using a Gel-pro analyzer (Media Cybernetics, CA, USA). We also analyzed the p16 and MGMT gene expressions by performing immunohistochemical staining of the HCC tissues. RESULTS: Methylation of the p16 promoter was detected in HCC (100%, 24/24) and the adjacent non-tumorous tissues (79.2%, 19/24), but not in the normal liver tissues. Methylation of the MGMT promoter was detected in the HCC (8.3%, 2/24) and the adjacent non-tumorous tissues (4.2%, 1/24), but not in the normal liver tissues. Methylation positive HCC samples showed the loss of p16 expression in 58.3% (14/24). The loss of the p16 expression in the HCC tissues was well correlated with the increased rate of p16 promoter methylation (p=0.009). When the p16 promoter methylation status of the HCC tissues was higher than that of the adjacent non-tumorous tissues, 77.8% of the cases showed the loss of the p16 expression (p=0.002). No correlation was observed between MGMT promoter methylation and the loss of the gene expression in the HCC tissues. CONCLUSION: These results suggest that methylation of the p16 promoter and the resulting loss of p16 protein expression are significant events in hepatocarcinogenesis, and further studies are needed to evaluate the relationship between the methylation of the MGMT promoter and HCC carcinogenesis.

Solitary Intra-abdominal Tuberculous Lymphadenopathy Mimicking Duodenal GIST

Tuberculosis remains prevalent in developing countries and has recently re-emerged in the Western world. Intra-abdominal tuberculosis can mimic a variety of other abdominal disorders, and here we describe a patient with solitary tuberculous mesenteric lymphadenopathy mimicking duodenal gastrointestinal stromal tumor (GIST). A 22-year-old woman complained of epigastric discomfort and was presumed to have a duodenal GIST after an endoscopic examination and abdominal CT scan. However, exploratory laparotomy revealed an enlarged node penetrating the duodenal bulb, which was diagnosed histopathologically as tuberculous lymphadenitis. This case suggests that in regions with a high prevalence of tuberculosis, intra-abdominal tuberculosis is often mistaken as a malignant neoplasm. A high index of suspicion and the accurate nonsurgical diagnosis of intra-abdominal tuberculosis continues to be a challenge.

Expression of Vascular Endothelial Growth Factor (VEGF) in Papillary Thyroid Carcinoma

PURPOSE: Papillary thyroid carcinomas are hypervascular tumors. The tumor growth and their metastases are dependent on factors that stimulate vessel formation (angiogenesis). Vascular endothelial growth factor (VEGF) has been reported to play an important role in the angiogenesis in papillary thyroid carcinomas in terms of the clinicopathological prognostic factors. METHODS: The expression of VEGF in specimens surgically removed from 23 papillary thyroid cancer patients were examined by immunohistochemical methods. RESULTS: The rate of VEGF expression was 56.5% in the tumor cells. The degree of VEGF expression was significantly correlated with local lymph node metastases (P=0.029) and the tumor extent (P=0.036). However, the degree of VEGF expression did not correlate with any clinicopathological characteristics. CONCLUSION: VEGF expression can be a useful prognostic factor of papillary thyroid carcinomas.

Serum Vascular Endothelial Growth Factor (VEGF) and Microvessel Tumor Invasion in Hepatocellular Carcinomas

PURPOSE: Vascular endothelial growth factor (VEGF) is a potent angiogenic factor in a number of cancers. The aim of this study was to evaluate the clinical significance of the serum level of VEGF in hepatocellular carcinoma (HCC) patients. METHODS: Serum VEGF was measured by an enzyme linked immunosorbent assay (ELISA) method. The correlation between serum VEGF level and clinico-pathological data of HCC patients were evaluated. RESULTS: The serum VEGF levels significantly increased with increasing tumor size and platelets count. The mean serum VEGF level in HCC patients with microvessel tumor invasion was higher than in those without microvessel tumor invasion. CONCLUSION: A high serum VEGF level may be an indicator of tumor progression and an important predictor of microvessel tumor invasion.

Cyclooxygenase-2 Expression in Intrahepatic Cholangiocarcinoma / 한국간담췌외과학회지

BACKGROUND/AIMS: Cyclooxygenase (COX)-2 levels are elevated in several types of human cancer tissues. COX-2 is not constitutively expressed by most normal tissues, but it is rapidly induced by certain inflammatory cytokines, tumor promoters, growth factors and oncogenes. Inflammation is important risk factor for intrahepatic cholangiocarcinoma. Therefore, this study was aimed to evaluate the role of COX-2 in intrahepatic cholangiocarcinoma development. METHODS: 18 intrahepatic cholangiocarcinoma patients was conducted in this study. COX-2 expression was investigated by immunohistochemical staining in resected liver specimen that involved 47 hyperplasia, 30 low-grade dysplasia, 38 high- grade dysplasia and 18 cancer. The relationship of clinicopathological factor and COX-2 expression of cancer was evaluated. RESULTS: COX-2 expression was not observed in normal bile duct epithelium. COX-2 expression in high-gade dysplasia was higher than in low-grade dysplasia. COX-2 expression in cancer was higher than in hyperplasia, low-grade and high grade dysplasia. There was no significant correlation between clinicopathological factors and COX-2 expression in cancer. CONCLUSION: These findings suggest that COX-2 may play a role in the early and late carcinogensis of intrahepatic cholangiocarcinoma.

Serum Vascular Endothelial Growth Factor after Transcatheter Arterial Chemoembolization in Patients with Hepatocellular Carcinoma / 한국간담췌외과학회지

BACKGROUND/AIMS: Vascular endothelial growth factor (VEGF) is a potent angiogenic factor. Hepatocellular carcinoma (HCC) is a typical hypervascular tumor and VEGF may play a important role in its carcinogensis and progression. Transcatheter arterial chemoembolization (TACE) which is one of the therapeutic modalities of HCC induces hypoxia to the tumor. VEGF is known to be up-regulated by hypoxia. In this study, we examined the level of VEGF in the course of TACE. METHODS: Twenty-two HCC patients were enrolled in this study. Serum VEGF level was investigated before and 1, 5 and 10 days after TACE. The correlation of clinical factors of patients and the level of serum VEGF before TACE was evaluated. Platelet count was also measured with VEGF. RESULTS: Mean serum VEGF level increased significantly 1 and 5 days after TACE. Platelet count decreased significantly 1 day after TACE. Serum VEGF level was positively correlated with platelet count before and 1 day after TACE. CONCLUSION: TACE may increase the serum level of VEGF induced by hypoxia.

Study of Genomic Heterogeneity of Hepatocellular Carcinomas by Using Arbitrary Primer Polymerase Chain Reaction (AP-PCR) / 한국간담췌외과학회지

BACKGROUND/AIMS: Discrimination between intrahepatic metastasis (IM) and de novo multicentric occurrence (MO) in multiple hepatocellular carcinoma (HCC) is important not only for the study of hepatocarcinogenesis but also for determination of therapeutic strategies. The purpose of this study is to evaluate the clonality of multiple or recurrent hepatocelluar carcinoma by using AP-PCR. METHODS: Paraffin-embedded blocks of 9 multiple synchronous hepatocellular carcinomas, one recurrent hepatocellular carcinoma and one combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma were used. None of the tumors was larger than 3.3 cm in diameter. Microdissection was done by using sterile 27 gauge needles and microscope. Two different arbitrary primers (AR3, ZF3) were utilized in AP- PCR. The clonality of tumor was assessed by DNA band pattern (DNA fingerprint) of PCR product. RESULTS: Eight of nine multiple synchronous hepatocellular carcinomas had distinctly different DNA fingerprints. One recurrent hepatocellular carcinoma and one combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma also had different DNA fingerprints. CONCLUSION: AP-PCR is a simple and very powerful method for determining the clonality of multiple hepatocellular carcinomas. The majority of multiple, small-sized hepatocellular carcinomas have different clonalities and it seems that a significant number of multiple hepatocellular carcinomas are of multicentric, de novo nature.

Expression of Vascular Endothelial Growth Factor (VEGF) and Microvessel Density in Hepatocellular Carcinoma / 한국간담췌외과학회지

BACKGROUND/AIMS: Hepatocellular carcinoma is a typical hypervascular tumor. Growth of tumor and their metastases are dependent on factors that stimulate vessel formation (angiogenesis). Vascular endothelial growth factor (VEGF) has been reported to play an important role in angiogenesis in hepatocellular carcinoma. The present study examined VEGF expression immunohistochemically in hepatocellular carcinoma in clinicopathological prognostic factors. METHODS: We examined the VEGF expression and microvessel density in specimens surgically removed from 37 HCC patients by immunohistochemical methods. RESULTS: The expression rate on VEGF was 43.2% in tumor cells. The degree of VEGF expression was significantly correlated with cumurative survival rate (p=0.034). But the degree of VEGF expression did not correlate with any clinicopathological characteristics (p.0.05). VEGF expression demonstrated no correlation with microvessel density (p=0.064). CONCLUSIONS: Our findings suggest that VEGF expression can be useful prognostic factor (survival rate) of hepatocellular carcinoma.

Expression of Cyclooxygenase-2 in Colorectal Adenocarcinoma

PURPOSE: Several studies indicate that nonsteroidal anti-inflammatory drugs including aspirin and sulindac reduce the risk of colon cancer. Futhermore, nonsteroidal anti-inflammatory drugs that inhibit the cyclooxygenase (COX) are shown to inhibit the development colon cancer in animal models of carcinogenesis. COX-1 is constitutively expressed to fulfill its beneficial housekeeping roles. COX-2 is not constitutively expressed by most normal tissues, but it is rapidly induced by certain inflammatory cytokines, tumor promoters, growth factors and oncogenes. The purpose of this study is to evaluate the role of COX-2 in colorectal carcinoma development and the correlation between COX-2 expression and tumor angiogenesis and p53 overexpression. METHODS: Immunohistochemical analyses using antibodies against COX-2, factor VIII-related antigen, vascular endothelial growth factor (VEGF) and p53 were carried out on archival specimens of 15 colorectal adenoma and 41 adenocarcinoma. RESULTS: COX-2 expression was increased in 5/15 (33.3%) adenomas and 24/41 (58.5%) adenocarcinomas. COX-2 expression in adenocarcinoma was nearly significantly higher than in adenoma (P=0.050). In adenocarcinoma, COX-2 expression was increased in early cancer (TNM stage) (P=0.028) and well differentiated tumor (P=0.029). COX- 2 expression was not correlated with VEGF expression, microvessel density and p53 overexpression. CONCLUSIONS: These findings indicate that enhanced expression of COX-2 occurs early during colorectal cancer progression. However, further investigations are needed to evaluate the relationship of COX-2 and tumor angiogenesis using other laboratory methods.

Resection of Colorectal Liver Metastases / 한국간담췌외과학회지

BACKGROUNDING/AIMS: It has been nearly established that liver resection for colorectal metastases is a relatively safe procedure with survival benefit to patients. This study was performed to evaluate if the liver resection for colorectal metastases is effective method and to determine the appropriate therapeutic modality. METHODS: Between January 1995 and January 1999, sixteen patients who had liver resectin for metastatic colorectal carcinoma at our hospital were analyzed retrospectively. RESULTS: Wedge resection was performed in 7 patients, segmentectomy in 3 patients, and lobectomy in 6 patients. The median survival time was 26 months and cumulative 1 and 4-year survival rate were 83.1% and 34.6%, respectively. Extent of hepatic resection had marginally influenced the survival(p=0.0514). No prognostic factor was related significantly to survival. Recurrence in remaining liver following the anatomical liver resection was significantly low compared with wedge resection( 12.5% vs. 71.5%, p=0.035). CONCLUSION: Liver resection is an effective and safe treatment for colorectal liver metastases. The anatomical liver resection decreased recurrence rate in the remnant liver. The curative resection with an adequate surgical margin will improve outcome.

Expression of Vascular Endothelial Growth Factor (VEGF) and p53 in Colorectal Cancer

PURPOSE: Neovascularization has been shown to be essential for the growth of solid tumors. Vascular endothelial growth factor (VEGF) is one of the most important mediators of angiogenesis, and recent studies have demonstrated that the p53 tumor suppressor gene plays an important role in controlling tumor angiogenesis. We examined the expression of VEGF and p53 as a function of microvessel density to evaluate its clinical significance in colorectal cancer and to investigate the correlation of VEGF and p53. METHODS: The study material included 20 patients who survived more than 5 years postoperatively without distant metastasis (non-metastasis group) and 21 patients who had synchronous (10 patients) and metachronous (11 patients) metastasis (metastasis group). Immunohistochemical staining for VEGF, p53 protein and factor VIII-related antigen was done. RESULTS: The expression rate of VEGF was 20% in non-metastatic tumors and 71% in metastatic tumors (p<0.05). The VEGF expression was not correlated with microvessel density. Otherwise, the microvessel density were 32.9 9.1 in non-metastatic tumors and 40.1 12.0 in metastatic tumors (p<0.05). VEGF expression was correlated with p53 over expression. CONCLUSION: VEGF expression might be a useful prognostic factor for metastasis in colorectal cancer. Also, our findings suggest the presence of a p53-VEGF pathway in colorectal cancer.