Expression In Colorectal Carcinoma Research Articles

Promoter hypomethylation and reactivation ofMAGE-A1andMAGE-A3genes in colorectal cancer cell lines and cancer tissues

To verify the expression and methylation status of the MAGE-A1 and MAGE-A3 genes in colorectal cancer tissues and cancer cell lines. We evaluated promoter demethylation status of the MAGE-A1 and MAGE-A3 genes by RT-PCR analysis and methylation-specific PCR (MS-PCR), as well as sequencing analysis, after sodium bisulfite modification in 32 colorectal cancer cell lines and 87 cancer tissues. Of the 32 cell lines, MAGE-A1 and MAGE-A3 expressions were observed in 59% and 66%, respectively. Subsequent to sodium bisulfite modification and MS-PCR analysis, the promoter hypomethylation of MAGE-A1 and MAGE-A3 was confirmed in both at 81% each. Promoter hypomethylation of MAGE-A1 and MAGE-A3 in colorectal cancer tissues was observed in 43% and 77%, respectively. Hypomethylation of MAGE-A1 and MAGE-A3 genes in corresponding normal tissues were observed in 2% and 6%, respectively. The promoter hypomethylation of MAGE genes up-regulates its expression in colorectal carcinomas as well as in gastric cancers and might play a significant role in the development and progression of human colorectal carcinomas.

A genome-wide map of aberrantly expressed chromosomal islands in colorectal cancer

BackgroundCancer development is accompanied by genetic phenomena like deletion and amplification of chromosome parts or alterations of chromatin structure. It is expected that these mechanisms have a strong effect on regional gene expression.ResultsWe investigated genome-wide gene expression in colorectal carcinoma (CRC) and normal epithelial tissues from 25 patients using oligonucleotide arrays. This allowed us to identify 81 distinct chromosomal islands with aberrant gene expression. Of these, 38 islands show a gain in expression and 43 a loss of expression. In total, 7.892 genes (25.3% of all human genes) are located in aberrantly expressed islands. Many chromosomal regions that are linked to hereditary colorectal cancer show deregulated expression. Also, many known tumor genes localize to chromosomal islands of misregulated expression in CRC.ConclusionAn extensive comparison with published CGH data suggests that chromosomal regions known for frequent deletions in colon cancer tend to show reduced expression. In contrast, regions that are often amplified in colorectal tumors exhibit heterogeneous expression patterns: even show a decrease of mRNA expression. Because for several islands of deregulated expression chromosomal aberrations have never been observed, we speculate that additional mechanisms (like abnormal states of regional chromatin) also have a substantial impact on the formation of co-expression islands in colorectal carcinoma.

Correlations of telomere length, telomerase activity, and telomeric‐repeat binding factor 1 expression in colorectal carcinoma

Telomere maintenance has been proposed as an essential step for tumor cell immortalization. The objectives of the current study were to investigate the mechanisms implicated in telomere length in colorectal carcinoma (CRC) and to evaluate the prognostic impact of telomere status. Ninety-one colorectal carcinoma samples that were obtained from patients who underwent surgery were analyzed to investigate the factors related to telomere function. The authors studied telomerase activity, terminal restriction fragment (TRF) length, and telomeric-repeat binding factor (TRF1) expression and analyzed the prognostic implications of those factors. Most tumors (81.3%) displayed telomerase activity. Overall, telomeres in CRC specimens were significantly shorter compared with telomeres in normal, adjacent specimens (P=0.02). Moreover, tumors that demonstrated shortened telomeres displayed higher TRF1 levels than tumors without telomere shortening. In relation to patient prognosis, a significantly poor clinical course was observed in the group of patients who had tumors with longer telomeres (P=0.02), and this finding emerged as an independent prognostic factor in a Cox proportional hazards model (P=0.04; relative risk, 6.48). Among patients with tumors classified as telomerase-positive, telomere length ratios (the ratio of tumor tissues to normal tissues)<or=0.66 or TRF1 over-expression conferred a favorable outcome (P=0.03 and P=0.05, respectively). The majority of CRC specimens in the current study displayed telomerase reactivation. However, only those tumors that displayed telomere elongation conferred a poor prognosis. Conversely, colorectal tumors that over-expressed TRF1 demonstrated telomere shortening, and patients with those tumors had a better clinical course.

Prognostic significance of bcl-2 and p53 expression in colorectal carcinoma

This study was designed to detect the expression of bcl-2 and p53 proteins in colorectal carcinomas and to determine their association with the patient survival and stage of the diseases. Immunohistochemistry method was used to detect the expression of bcl-2 and p53 proteins in 93 cases of colorectal carcinoma. The stain results were obtained by analyzing the clinic-pathological characteristics of patients. Fifty-seven percent (53/93) of the colorectal carcinomas were bcl-2 protein positive. The positive rate of bcl-2 protein in lymph node involvement cases was lower (15/37) than the cases without node involvement (38/58, P<0.01). The positive rate of p53 protein was 43% (40/93) in colon-rectum carcinomas. No significant correlation was observed between p53 protein expression and clinic-pathological manifestations (P>0.05) but the survival was significantly worse (P=0.0001) in the p53 protein positive cases. Neither bcl-2 nor p53 alone was correlated with stage of the disease. When combined bcl-2/p53 status was analyzed, a group with bcl-2(+) and p53(-) had the best prognosis. This group was significantly associated with earlier Dukes' stages (P=0.1763). In multivariate Cox regression analysis, lymph node involvement and p53 protein expression were two independent factors correlated with survival time. The expression of bcl-2 and p53 represent biological characteristics of colorectal carcinomas. Assessment of both bcl-2 and p53 status may be valuable in predicting the prognosis of patients.

CD10 Expression in Colorectal Carcinoma Correlates With Liver Metastasis

If it were possible to identify the features of primary colorectal carcinoma that were associated with liver metastasis, these features could be used as predictors of liver metastasis. From January 1995 to December 1997, 648 consecutive cases of colorectal carcinoma were recorded at the Department of Surgery, National Cancer Center Hospital, Tokyo, Japan. We evaluated clinicopathologic and immunohistochemical factors (age, gender, tumor location, gross type, size, histologic type, dedifferentiation of invasive front, depth of invasion, lymphatic invasion, venous invasion, lymph-node metastasis, and expression of CD10, MUC2, and human gastric mucin) in 505 of these patients who had undergone resection of T2/T3/T4 colorectal carcinomas to clarify the correlation between these factors and liver metastasis. Liver metastases, including unresectable, were detected in 122 patients (24 percent), all of whom had been followed for at least five years. Univariate analysis revealed that liver metastasis was significantly associated with tumor size, histologic type, dedifferentiation of invasive front, depth of invasion, lymphatic invasion, venous invasion, lymph-node metastasis, and CD10 expression. Multivariate analysis revealed that invasion deeper than the subserosa, venous invasion, lymph-node metastasis, and CD10 expression were significantly associated with liver metastases. CD10 expression in colorectal carcinoma is a good predictor of liver metastasis.

Metabotropic Glutamate Receptor 4 Expression in Colorectal Carcinoma and Its Prognostic Significance

Metabotropic glutamate receptors (mGluR) play a variety of roles in both neuronal and nonneuronal cells. Recently, we reported that mGluR4 mediates 5-fluorouracil resistance in a human colon cancer cell line. In this study, we evaluated the nonneural expression of mGluR4 and clarified the existence of mGluR4 in normal colon epithelium and colorectal carcinomas. We also investigated the association of mGluR4 expression levels with various clinicopathologic parameters. mGluR4 expression was investigated in 21 normal and 312 malignant tissues from various organs using immunohistochemistry. In addition, 241 cases of colorectal carcinomas were examined and correlations between mGluR4 expression and various clinicopathologic parameters were then statistically analyzed. Expression of mGluR4 was identified in the normal epithelia of the upper respiratory tract, gastrointestinal tracts, breast, uterine cervix, urinary bladder, and skin, whereas it was not detected in the thyroid, lung alveoli, liver, testis, or prostate. In the corresponding malignant tissues, mGluR4 expression was frequently identified in colorectal carcinoma (68%), followed by malignant melanoma, laryngeal carcinoma, and breast carcinomas. Expression of mGluR4 was detected in 131 (54%) of 241 colorectal carcinomas and 12 (5%) cases among them showed overexpression in their cytoplasms. Loss of mGluR4 expression was negatively associated with tumor differentiation (P = 0.028), whereas overexpression of mGluR4 was positively associated with recurrence (P = 0.034) and poor disease-free survival (P = 0.017) in multivariate analyses. Our results suggest that mGluR4 signaling may play a role in colorectal carcinomas and that overexpression of mGluR4 is associated with poor prognosis.

Promoter methylation downregulates CDX2 expression in colorectal carcinomas

CDX2 (caudal type homeobox transcription factor 2) is a homeobox protein, which is expressed in intestinal epithelium. CDX2 has been considered to play a role as a tumor suppressor gene in colorectal cancer because its expression is lacking in colorectal carcinomas, but preserved in adenomas. The point mutations have been found to account for loss of CDX2 expression, but the main mechanism responsible for CDX2 gene inactivation is less understood. We analyzed methylation and expression status of CDX2 in colorectal cancer cell lines and primary tumors. There are two CpG-rich sites in promoter region of CDX2 gene, -1570 to -1200 and -220 to +880. By COBRA (combined bisulfite restriction analysis) assay, the upper CpG-rich site was heavily methylated in all cell lines, but the lower CpG-rich site was methylated in limited cell lines. Bisulfite sequencing analysis and RT-PCR revealed that methylation of the lower CpG site was associated with down-regulation of CDX2. In addition, gene expression was restored in COLO201, a methylated cell line with 5-aza-2'-deoxycytidine, confirming that methylation caused gene down-regulation. We also examined CDX2 promoter methylation of primary tumors by MSP (methylated-allele specific PCR) assay and found that nearly 40% of cases have a methylated CDX2 gene. Our results demonstrate that CDX2 methylation is frequently present in colorectal cancers and may play a key role in inactivating CDX2 expression.

Ornithine decarboxylase gene is overexpressed in colorectal carcinoma

To investigate the ornithine decarboxylase (ODC) gene expression in colorectal carcinoma, ODC mRNA was assayed by RT-PCR and ODC protein was detected by a monoclonal antibody against fusion of human colon ODC prepared by hybridoma technology. Total RNA was extracted from human colorectal cancer tissues and their normal counterpart tissues. ODC mRNA levels were examined by RT-PCR. ODC genes amplified from RT-PCR were cloned into a prokaryotic vector pQE-30. The expressed proteins were purified by chromatography. Anti-ODC mAb was prepared with classical hybridoma techniques and used to determine the ODC expression in colon cancer tissues by immunohistochemical and Western blotting assay. A cell line, which could steadily secrete anti-ODC mAb, was selected through subcloning four times. Western blotting reconfirmed the mAb and ELISA showed that its subtype was IgG2a. RT-PCR showed that the ODC mRNA level increased greatly in colon cancer tissues (P<0.01). Immunohistochemical staining showed that colorectal carcinoma cells expressed a significantly higher level of ODC than normal colorectal mucosa (98.6+/-1.03% vs 5.26+/-5%, P<0.01). ODC gene overexpression is significantly related to human colorectal carcinoma. ODC gene expression may be a marker for the gene diagnosis and therapy of colorectal carcinoma.

B7molecule mRNA expression in colorectal carcinoma

To observe the status of tumor-associated B(7) molecule mRNA expression in human colorectal cancer tissue by in situ hybridization. The mRNA expression patterns of cancer-associated B(7-1),B(7)H(1),B(7)H(2),ICOS in 22 specimens of human colorectal cancer tissue were monitored by in situ hybridization (ISH) with digoxin-labeled oligonucleotide probes. B(7-1),B(7)H(1),B(7)H(2),ICOS mRNA were detected in both cancer cells and tumor infiltrating lymphocytes (TIL). The mRNA expression level of these molecules in tumor cells was higher than that in TIL (0.76+/-0.54 - 1.62+/-0.82 vs 0.38+/-0.19 - 0.65+/-0.33, P<0.001). There was no relationship between expression level of tested B(7) family molecules and patients' sex, age, differentiation status of cancer and regional lymph node metastasis. Th2 cytokine predominant in tumor microenvironment might be related to the expression of B(7)H(1),B(7)H(2) co-signal molecules in tumor cells and TIL.

Use of novel immunohistochemical markers expressed in colonic adenocarcinoma to distinguish primary ovarian tumors from metastatic colorectal carcinoma

Distinguishing primary ovarian carcinoma, particularly endometrioid and mucinous subtypes, from metastatic colorectal carcinoma to the ovary is often difficult on histologic examination alone. Recently, three immunohistochemical markers CDX2, a homeobox gene encoding an intestine-specific transcription factor; α-methylacyl-CoA racemase (AMACR/P504S), a mitochondrial and peroxisomal enzyme with fairly restricted expression in selective tumors and β-catenin, an adenomatous polyposis coli (APC) mutation product resulting in activation of the Wnt pathway, have been reported to have specific and sensitive expression in colorectal carcinomas. We evaluated a panel consisting of antibodies to CDX2, β-catenin and P504S in 23 primary ovarian adenocarcinomas (13 mucinous and 10 endometrioid) and compared the findings to 22 metastatic colorectal adenocarcinomas (seven mucinous and 15 nonmucinous tumors with endometrioid-like morphology hereafter referred to as pseudo-endometrioid) to the ovary stained with the same panel. Twenty (91%) metastatic tumors expressed at least two markers and seven (32%) expressed all three. In contrast, only three (13%) primary ovarian tumors expressed at least two markers and none expressed all three. Strong (2+, 3+) and diffuse (>40%) expression for CDX2 was noted in 21 (95%) metastatic tumors and five (22%) primary ovarian tumors (three mucinous, two endometrioid). P504S was similarly expressed in seven (32%) metastatic and none of the primary ovarian carcinomas. Nuclear expression of β-catenin was noted in 13 (59%) metastatic tumors and in eight cases (36%), it was diffuse and strong. In contrast, four (19%) primary tumors showed nuclear expression of this protein with only one (5%) case expressing it in a diffuse pattern. Immunohistochemical expression of gene products and enzymes of colorectal carcinogenesis in some primary ovarian carcinomas suggest that the morphologic similarities between colorectal and mucinous/endometrioid carcinoma of the ovary extends to the genetic level, although differences in the level of expression exist between these tumors. Diffuse expression of all three markers (CDX2, β-catenin and P504S) in a tumor in the ovary was found to be virtually diagnostic of metastasis from a colorectal primary in this study.

CDX1 expression is reduced in colorectal carcinoma and is associated with promoter hypermethylation.

The CDX1 homeobox gene encodes a transcription factor specifically expressed in normal intestinal and colonic epithelia, and CDX1 gene expression is affected during colorectal tumour progression. In this study, real-time quantitative RT-PCR was used to investigate CDX1 expression in 26 colorectal carcinomas. Reduced expression of CDX1 was observed in 19 of 26 colon carcinomas compared to matched normal colonic mucosa: the decrease in CDX1 expression ranged between 0.10 and 0.79 (21-90% decrease; mean 64.75% +/-22; p = 0.001). Mutation and loss of heterozygosity (LOH) analyses were then used to determine if reduced CDX1 expression was due to genetic alteration. No CDX1 gene mutations, but two known polymorphisms in exon 1, were observed. LOH was observed in 33% of the tumours investigated but this was not related to CDX1 expression. Since aberrant promoter methylation is a well-known mechanism that participates in gene silencing, the methylation status of the CDX1 5' CpG island promoter was also investigated. PCR amplification of bisulphite-treated DNA followed by cloning was performed in 7 carcinomas that showed low expression of CDX1 and in 1 colonic carcinoma without reduced expression. Promoter hypermethylation occurred in carcinomas in which CDX1 reduced expression was present. These results suggest that CDX1 promoter hypermethylation is one of the molecular mechanisms that accounts for reduced CDX1 gene expression in colorectal carcinoma.

Prognostic significance of matrix metalloproteinase-2, cathepsin D, and tenascin-C expression in colorectal carcinoma

Matrix metalloproteinase-2 (MMP-2) and cathepsin D (CD) play a significant role in degrading the components of basement membrane and extracellular matrix (ECM), whereas tenascin-C (TN-C) is a glycoprotein of the ECM related to cell adhesion and detachment. These proteins have been implicated in tumor invasion and metastasis. Therefore, we aimed at investigating the prognostic significance of MMP-2, CD, and TN-C expressions in primary colorectal cancer. Overall, 112 colorectal adenocarcinomas were included in the present study. MMP-2, CD, and TN-C expressions were evaluated by immunohistochemistry and correlated with clinicopathologic prognostic parameters and survival. Diffuse stromal TN-C immunostaining was found to be significantly correlated with advanced stage and shorter survival time ( p=0.002 and 0.02, respectively). MMP-2 expression was found to correlate with lymph vessel invasion ( p=0.006) and stage ( p=0.03). CD expression was related to depth of invasion ( p=0.005). No significant relationship was found between survival and MMP-2 and CD expression ( p>0.05). In multivariate analysis, stage and vascular invasion were independent prognostic factors, whereas TN-C did not retain a clear independent relationship to survival ( p>0.05). Our findings suggest that TN-C expression may be a potential prognostic marker in colorectal carcinoma. However, MMP-2 and CD do not appear to be significant indicators of survival.

Cyclooxygenase-2 and c-erbB-2 expression in colorectal carcinoma assessed using tissue microarrays.

The c-erbB-2 and cyclooxygenase (COX) pathways are involved in the pathogenesis of colorectal carcinoma, but the relationship is not fully understood. This study evaluated the significance of c-erbB-2, COX-2, and Ki-67 protein expression in 185 patients with colorectal carcinoma using tissue microarrays. Only one case expressed cerbB-2 protein. COX-2 expression was noted in 166 of 176 cases (94.3%), and the Ki-67 expression rate averaged 5.9%. There was no relationship among c-erbB-2, COX-2, and Ki-67 protein expression, and COX-2 protein expression was not related to tumor stage, differentiation, size, depth of invasion, lymphatic or vascular invasion, or patient survival. While the contribution of c-erbB-2 to colorectal carcinogenesis may be of little quantity, COX-2 may be deeply involved in colorectal carcinogenesis.

Loss of CDX1 expression in colorectal carcinoma: promoter methylation, mutation, and loss of heterozygosity analyses of 37 cell lines.

Expression of the homeobox protein CDX1 is lost or reduced in a significant proportion of colorectal carcinomas (CRCs) but the underlying mechanism for this is unclear. We have demonstrated absence of CDX1 mRNA expression in 7 of 37 CRC cell lines and shown that all 7 cell lines have a methylated CDX1 promoter. Twenty-five cell lines showed both CDX1 mRNA expression and an unmethylated CDX1 promoter. The five remaining cell lines had a partially methylated CDX1 promoter and all expressed CDX1 mRNA; when treated with the demethylating agent, 5-aza-2'-deoxycytidine, these five cell lines all showed increased CDX1 expression. No mutations were found in the promoter and coding regions of CDX1. One polymorphism was demonstrated in each of the promoter, 5' UTR, and coding region of exon 1 of CDX1, but there were no associations between CDX1 mRNA expression and different polymorphic genotypes. Similarly, there was no association between CDX1 mRNA expression and loss of heterozygosity at the CDX1 locus. In conclusion, absence or reduction of CDX1 expression in CRC seems to be primarily regulated by promoter methylation and is probably selected for because of its impact on the differentiation of colonocytes.

Expression of survivin and its significance in colorectal cancer.

To study the expression of survivin, a novel member of inhibitors of apoptosis protein (IAP) and its significance in colorectal carcinoma. Survivin mRNA expression was evaluated by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in 52 colorectal carcinoma samples and 48 adjacent normal colorectal tissue samples. PCR product was sequenced to verify the desired result. Expressions of survivin protein, proliferating cell nuclear antigen labelling index (PI) and apoptotic index (AI) were detected immunohistochemically in 52 human colorectal carcinomas. The expression of survivin mRNA was detected in a significantly greater proportion of colorectal carcinoma samples than in adjacent normal colorectal tissues (67.3% vs 25%; P<0.01). There was no relationship between survivin mRNA expression in colorectal carcinomas and sex, tumor size, histological types, lymphnode metastasis, distant metastasis and Dukes' stage. The PCR product shared 99% of homology with human counterparts. Survivin expression was observed immunohistochemically in 27 of 52 cases of colorectal carcinoma (51.9%). The AI was significantly lower in survivin positive group than in survivin negative group (0.67+/-0.18% vs 1.14+/-0.42%; P<0.001), while the PI was greater in survivin positive group than in survivin negative group (51+/-22% vs 27+/-18%, P<0.001). Survivin is a special tumor marker independent of histopathological characteristics. It may play an important role during human colorectal tumorigenesis by inhibiting apoptosis and accelerating proliferative activity of colorectal tumor cells.

Platelet-derived endothelial cell growth factor expression is an independent prognostic factor in colorectal cancer patients after curative surgery

Aims. Platelet-derived endothelial cell growth factor (PD-ECGF) is an angiogenic factor that undergoes increased expression in colorectal carcinomas, but its prognostic value is a topic of debate. The aim of this study is to clarify the prognostic value of PD-ECGF expression in colorectal carcinomas. Methods. PD-ECGF expression was measured by enzyme-linked immunosorbent assay in frozen materials from 134 colorectal cancer patients who had recived curative resections. Patients were divided into high expression and low expression groups based upon selected cut-off value. Correlations among PD-ECGF expression, clinicopathologic features, and disease-free interval were studied by univariate and multivariate analysis. To evaluate the origin of PD-ECGF, serial sections of the 134 tumours were stained for PD-ECGF and CD68. Results. PD-ECGF expression in the normal mucosa was 34.4±15.5 (Units/mg protein) and the cut-off value was 65.4 (mean+2SD). There were no significant correlations between clinicopathological features and PD-ECGF expression. The disease-free interval for the high PD-ECGF expression group was significantly longer than that of the low expression group ( P=0.05). A multivariate Cox's regression analysis revealed that high PD-ECGF expression is an independent factor for better outcome. In immunohistochemical study, almost all tumour cells were negative for PD-ECGF, but stromal macrophages were predominantly positive for PD-ECGF. Conclusions. The PD-ECGF expression originated from stromal macrophages was a predictor for favorable outcome after curative resections for colorectal cancer.

240 The potential role of TGF-beta-1, TGF-beta -2 and TGF-beta-3 proteins expression in colorectal carcinomas, and their possible correlation with classic histopathologic factors and patients survival

240 The potential role of TGF-beta-1, TGF-beta -2 and TGF-beta-3 proteins expression in colorectal carcinomas, and their possible correlation with classic histopathologic factors and patients survival

Frequency of loss of hMLH1 expression in colorectal carcinoma increases with advancing age.

The correlation between age at diagnosis and loss of expression of hMLH1 protein in patients with colorectal carcinoma (CRC) has not been evaluated systematically. Immunohistochemistry was performed for hMLH1 protein in tumor samples from 867 patients with CRC. The authors defined tumors arising in the cecum, ascending colon, and transverse colon as right-sided and tumors arising in the descending colon, sigmoid colon, and rectum as left-sided. Patients' gender, tumor location (side), and hMLH1 expression were analyzed by age groups. The percentage of tumors with hMLH1 expression loss increased significantly with advancing age (P < 0.0001): There were no tumors in patients age < 40 years that manifested loss of hMLH1 expression, compared with 29% of tumors that manifested loss of hMLH1 expression in patients age > 90 years. Loss of hMLH1 expression occurred more often in patients with right-sided tumors (32.7% vs. 5.2% of patients with left-sided tumors; P < 0.0001) and in tumors from female patients (24.3% vs. 11.5% of tumors from male patients; P < 0.0001). There was no evidence of interaction between gender and tumor location. Loss of hMLH1 expression in patients with CRC was associated strongly with increasing age. hMLH1 expression loss was more pronounced in tumors from female patients and in tumors that originated on the right side of the colon. Loss of hMLH1 expression in right-sided tumors occurred in nearly 50% of patients age > 90 years. This age-related trend also was observed for males and in tumors that originated in the left colon.

Significance of immunohistochemical expression of manganese superoxide dismutase as a marker of malignant potential in colorectal carcinoma

Manganese superoxide dismutase (MnSOD) is an important superoxide anion scavenger located in mitochondria and protects cells from the damage caused by reactive oxygen species. The oxygen balance has been reported to be related to the occurrence and invasiveness of malignant tumors. The aim of the current study was to elucidate the clinicopathological significance of immunohistochemical MnSOD expression in colorectal carcinoma. Consecutive 186 primary colorectal carcinomas which had been resected from 1987 to 1999 were examined for MnSOD expression by means of an immunohistochemical investigation. Sixty nine carcinomas (37.1%) had a positive response to MnSOD. The proportion of lymph node metastasis in MnSOD positive carcinomas (49.3%, 34 out of 69) was significantly higher than that in MnSOD negative carcinomas (26.5%, 31 out of 117; p=0.002). The proportion of patients classified to Dukes' stage A, B, C, and D in MnSOD positive carcinomas was 10.1, 33.3, 40.7, and 15.9%, respectively, and those were 23.1, 49.5, 24.8, and 2.6%, respectively in MnSOD negative carcinomas (p=0.0001). The survival rate in patients with MnSOD positive carcinomas was significantly worse than that in patients with MnSOD negative carcinomas (p=0.01). Multivariate analysis demonstrated that Dukes' stage of tumors was found to be a factor independently associated with prognosis of the patients. Our results showed that immunohistochemical expression of MnSOD can give auxiliary clinical information for malignant potential of colorectal carcinoma.

The prognostic significance of type IV collagen expression in colorectal carcinomas

BACKGROUND: Breakdown of basement membrane is believed to be an essential step for tumor invasion and metastasis. The interaction between tumor cells and extracellular matrix can also result in induction of basement membrane synthesis by tumor and stromal cells. The aim of this study was to investigate distribution patterns of type IV collagen expression at the basement membrane in the tumor tissue of colorectal carcinomas by immunohistochemical staining. The degree of expression of type IV collagen correlated with classical clinicopathologic prognostic factors and their potential relationship with patients' prognosis. PATIENTS AND METHODS: This study included 40 patients who underwent curative resection of colorectal cancer at the Department of Surgery in the General Hospital Senta with complete follow-up for 5 years or until death. The identification of basement membrane was performed immunohistochemically using monoclonal antibodies to collagen IV. The basement membrane synthesis at the invasive front of colorectal cancer was semiquantitatively assessed as mild, moderate or severe. RESULTS: The deposition of basement membrane type of collagen IV had a statistically significant correlation with the stage of disease and histological grade of tumor with tendency of lesser synthesis of basement membrane in the advanced stage of disease and poorer histological grade of tumor. There were no significant correlations between intratumoral basement membrane synthesis and sex and age of patients, and localization and histological type of tumor. Five-year survival rates in patients with mild synthesis of basement membrane in colorectal tumor were significantly lower than in patients with severe expression of basement membrane. The basement membrane synthesis in colorectal cancer was a prognostic factor with significance behind stage of disease and histological grade of tumor by univariate Cox hazard-model. Multivariate Cox analysis verified that explicit synthesis of basement membrane showed a trend toward better prognosis, but it was not statistically significant. CONCLUSION Immunohistochemical staining for type IV collagen is an important additional technique with prognostic value.