Indicator In Colorectal Cancer Research Articles

Lipocalin 2 performs contrasting, location-dependent roles in APCmin tumor initiation and progression

Evidence that lipocalin 2 (LCN2) is oncogenic has grown in recent years and comes from both animal models and expression analysis from a variety of human cancers. In the intestine, LCN2 is overexpressed in colitis patients and its overexpression is a negative prognostic indicator in colorectal cancer. Functionally, LCN2 has a number of different activities that may contribute to its oncogenic potential, including increasing matrix metalloproteinase activity, control of iron availability and stimulating inflammation. In this report, we examined APCmin intestinal tumorigenesis in an LCN2-deficient background. We found that the loss of LCN2 increased tumor multiplicity specifically in the duodenum, suggesting a potential tumor-suppressive activity. Concurrently, however, LCN2 increased the average small intestinal tumor size particularly in the distal small intestine. We found that this increase was correlated to tumor iron(II) content, suggesting that an iron-scavenging role is important for LCN2 oncogenic activity in the intestine.

Following the protein biomarker trail to colorectal cancer

93 ISSN 1758-194X 10.2217/CRC.12.7 © 2012 Future Medicine Ltd Colorect. Cancer (2012) 1(2), 93–96 1Department of Pathology, Aberdeen Royal Infirmary, NHS Grampian, Aberdeen, UK *Author for correspondence: Pathology, Division of Applied Medicine, School of Medicine & Dentistry, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK; Tel.: +44 1224 553794; Fax: +44 1224 663002; g.i.murray@abdn.ac.uk Colorectal cancer is the second most commonly diagnosed cancer in women and the third in men, with over 600,000 estimated annual deaths attributed to this disease [1]. The identification of protein biomarkers in colorectal cancer has diagnostic utility and, over the past decade, has accumulated growing prognostic and predictive importance. Classically, colorectal cancer is thought of as a slowly progressive disease following a defined pathway through aberrant crypt foci to adenoma formation, cumulating in invasive malignancy and eventually metastatic disease [2]. This morphological sequence was thought to be closely paralleled by a step-wise accumulation of molecular genetic events occurring over time, but it is now recognized that colorectal carcinogenesis is much more complex and likely results from an intricate interplay between numerous abnormal subcellular pathways with multiple interactions between the tumor cell and its microenvironment. It is therefore a highly heterogeneous group of diseases with variable outcomes observed between individual patients. In diagnostic medicine, gene-expression patterns and mutational ana lysis are increasingly being used for guiding ‘personalized’ cancer treatment. Genomic studies have also underpinned the identification of some potentially useful protein biomarkers in colorectal cancer. However, proteomic ana lysis of tumor tissue may more accurately reflect the true protein profile within malignant tissue, as this method directly assesses the global expression of proteins in test tissue rather than indirectly via gene-expression arrays [3–5]. Immunohistochemistry to detect protein biomarkers in formalin-fixed tissue is a robust analytical technique that is widely available in a laboratory setting at a relatively low cost. Currently used prognostic indicators in colorectal cancer include the pathological tumor-, node-, metastasisand imagingbased staging systems, with the presence or absence of extramural venous invasion and lymph node metastasis being key factors. Surgery remains the primary treatment for most cases of colorectal cancer, “...proteomic ana lysis of tumor tissue may more accurately reflect the true protein profile within malignant tissue, as this method directly assesses the global expression of proteins in test tissue rather than indirectly via gene-expression arrays.” EDITORIAL

MicroRNA-10b is a Prognostic Indicator in Colorectal Cancer and Confers Resistance to the Chemotherapeutic Agent 5-Fluorouracil in Colorectal Cancer Cells

Recent evidence has shown that altered patterns of microRNA (miRNA) expression correlate with various human cancers. We investigated the clinical significance of miR-10b and its involvement in chemotherapeutic resistance to 5-fluorouracil (5-FU), which is a key component of common chemotherapy regimens in colorectal cancer. Quantitative RT-PCR was used to evaluate the clinicopathologic significance of miR-10b expression in 88 colorectal cancer cases. We also investigated the chemotherapeutic sensitivity to 5-FU in miR-10b-overexpressing colorectal cancer cells. To explore the mechanism of chemoresistance in miR-10b transfected cells, we examined whether miR-10b inhibits the pro-apoptotic BH3-only Bcl-2 family member BIM(BCL2L11), a key mediator of chemotherapy-induced cell death. High level miR-10b expression was found to be significantly associated with high incidence of lymphatic invasion (P = 0.0257) and poor prognosis (P = 0.0057). Multivariate analysis indicated that high miR-10b expression is an independent prognostic factor for survival. In vitro studies revealed that miR-10b directly inhibits pro-apoptotic BIM, and the overexpression of miR-10b confers chemoresistance in colorectal cancer cells to 5-FU. MiR-10b is a novel prognostic marker in colorectal cancer. Moreover, the expression of miR-10b is a potential indicator of chemosensitivity to the common 5-FU-based chemotherapy regimen.

Temporal trends in geographic disparities in small-area-level colorectal cancer incidence and mortality in the United States

We examined the extent of changes in absolute and relative geographic disparities in six colorectal cancer (CRC) indicators using data about persons aged 50 and older from 195 counties in the 1988-2006 Surveillance, Epidemiology, and End Results Program database. County-level trends in six colorectal cancer indicators (overall CRC incidence, descending colon cancer incidence, proximal colon cancer incidence, late-stage CRC incidence, CRC mortality, and 5-year probability of CRC death) were summarized using the estimated annual percentage change. Observed county rates were smoothed using Bayesian hierarchical spatiotemporal methods to calculate measures of absolute and relative geographic disparity and their changes over time. During the study period, absolute disparity for all six indicators decreased (CRC incidence: 43.2%; proximal colon cancer: 31.9%; descending colon cancer: 52.8%; late-stage CRC: 50.0%; CRC mortality: 57.8%; 5-year CRC-specific probability of death: 12.2%). Relative disparity remained stable for all six indicators over the entire study period. Important progress has been made toward achieving the Healthy People 2010 and NCI strategic objectives for reducing geographic disparities, although absolute and relative disparities remain in CRC.

IL-2 as a prognostic indicator in colorectal cancer

IL-2 as a prognostic indicator in colorectal cancer

The Role of Tumour Stroma in Colorectal Cancer Invasion and Metastasis

Colorectal cancer (CRC) is a major cause of mortality in western society with a 5-year survival of approximately 50%. Metastasis to the liver and lungs is the principal cause of death and occurs in up to 25% of patients at presentation. Despite advances in available techniques for treating metastases, the majority of patients remain incurable and existing adjuvant therapies such as chemotherapy are only of limited effectiveness. Understanding the molecular mechanisms underlying the metastatic process may allow us to identify those at greatest risk of recurrence and discover new tumour targets to prevent disease progression. It is now apparent that tumour stroma plays an important role in promoting tumour progression. A pronounced desmoplastic reaction was associated with a reduced immune response and has been shown to be an independent poor prognostic indicator in CRC and cancer recurrence. Determining the cause(s) and effect(s) of this stromal response will further our understanding of tumour cell/stromal interactions, and will help us identify prognostic indicators for patients with CRC. This will not only allow us to target our existing treatments more effectively, we also aim to identify novel and more specific therapeutic targets for the treatment of CRC which will add to our current therapeutic options.

Telomere length maintenance: a factor to be considered in personalized medicine?

telomerase is required to sustain their growth. The fact that cancer cells have shorter telomeres than normal cells, together with the fact that cancer growth appears to depend on telomerase reactivation, indicates that therapeutic strategies that are aimed at inhibiting telomerase will preferentially kill the tumor cells and have no toxicity on normal cells [3]. Since telomerase and telomere maintenance play a key role in the development of malignancies, several approaches targeting either the telomerase enzyme or the telomeres have been developed. However, while many efforts have been carried out to discover new anti-telomere/telomerase drugs, to date, very few compounds are exploitable for clinical use owing to low effectiveness or toxicity in vivo and also because of our partial knowledge on telomere and telomerase regulation and its functions [4]. There is growing evidence that telomere length carries information that may be of clinical importance for cancer patients. It is well established that telomere length is important for senescence in normal cells and there appears to be a connection between telomere shortening, genetic aberrations and the risk of cell transformation. Interests in investigating telomere length as a potential clinical biomarker in cancer has grown considerably in recent years. For hematogical malignancies, published data demon strate that short telomeres indicate progressive disease and a poor outcome [5]. For solid tumors the data are more heterogeneous. Thus, in colorectal cancer (CRC) telomere reduction appears to occur in parallel in noncancerous mucosa and colon cancer, with a correlation between both. Functional studies have implicated human TRF1 in telomere length Telomeres form specialized structures at the ends of eukaryotic chromosomes, preventing them from being wrongly recognized as damaged DNA. In normal cells, the DNA replication machinery is unable to completely duplicate telomeric DNA; thus, telomeres are shortened after every cell division. When telomeres become critically shortened and compromise genomic stability, chromosome ends activate DNA damage response pathways that can induce apoptosis. In cancer, these mechanisms are often inactivated, and telomeres can become dysfunctional via several mechanisms, such as loss or alteration of telomere-binding proteins involved in telomere maintenance. These proteins are critical for the functions of telomeres as they prevent unwanted DNA repair activity [1]. Tumor cells acquire the hallmark properties of cancer during the carcinogenic selection process. Cell immortality is one of the principal features acquired, which involves the stabilization of telomere length. It is achieved mainly by telomerase activation. Thus, the discovery of telo meres and telomerase allowed an understanding of the mechanisms by which cells can become immortalized [2]. Generally tumors have shorter telomeres than the surrounding normal tissue, owing to the fact that they have had a longer proliferative history in the absence of telomerase activity. Telomere shortening can eventually lead to increased cell death and loss of cell viability within the tumor. However, telomerase is reactivated in more than 90% of all types of human tumor, thereby rescuing and perpetuating cells with short telomeres and high chromosomal instability. Similarly, most metastases also contain telomerase-positive cells, which indicate that

Prognostic Value of the Lymph Node Ratio in Stage III Colorectal Cancer: A Systematic Review

Although nodal invasion represents one of the most powerful prognostic indicators in colorectal cancer, marked heterogeneity exists within stage III patients. Recently, the lymph node ratio (LNR), defined as the ratio of the number of positive nodes over the total number of examined nodes, was proposed to stratify outcome in stage III patients. A systematic search was performed for studies examining the prognostic significance of the LNR in colon or rectal cancer. Individual studies were assessed for methodological quality and summary data extracted. Hazard ratios from multivariate analyses were entered in a fixed-effects meta-analysis model. In total, 16 studies were identified including 33,984 patients with stage III colon or rectal cancer. In all identified studies, the LNR was identified as an independent prognostic factor in patients with stage III cancer of the colon or rectum. The prognostic separation obtained by the LNR was superior to that of the number of positive nodes (N stage). The pooled hazard ratios for overall and disease-free survival were 2.36 (95% confidence interval, 2.14-2.61) and 3.71 (95% confidence interval, 2.56-5.38), respectively. The LNR allows superior prognostic stratification in stage III colorectal cancer and should be validated in prospective studies.

PWE-069 Colorectal cancer lymphatics display an altered phenotype associated with lymph node metastasis

<h3>Introduction</h3> Tumour cell metastasis to lymph nodes is a frequent clinical feature of colorectal cancer and often heralds a poor clinical outcome. Although tumoural lymphangiogenesis is assumed to contribute to this process there is little evidence to support any notion of a simple correlation between lymphatic vessel density and colorectal cancer metastasis. Growing evidence of complex functional and biochemical interactions between tumour cells and the tumour microvasculature imply that tumoural lymphatics may possess specific phenotypes capable of facilitating tumour cell entry and spread to draining lymph nodes. <h3>Methods</h3> We compared the RNA profile of primary lymphatic endothelial cells isolated from tumour and normal tissue using the lymph node metastasising murine T-241/VEGF-C fibrosarcoma model. These results were validated immunohistochemically in several human cancers, including colorectal cancer. The prognostic significance of two differentially expressed genes on tumoural lymphatics was assessed by immunofluorescence microscopy on a panel of mixed stage colorectal cancer tissues. <h3>Results</h3> We reveal significant differences in the expression of some 792 genes between normal and tumour lymphatic endothelial cells (ie, &gt;2× fold up/downregulation). These include genes that code for a variety of proteins including components of endothelial junctions, subendothelial matrix, and vessel growth/patterning. We investigated two of these differentially expressed genes in colorectal cancer; Endothelial Specific Adhesion Molecule (ESAM), a tight junction regulatory protein, and Endoglin (CD105), the transforming growth factor-β coreceptor. We reveal that ESAM and Endoglin are significantly upregulated on the lymphatics of colorectal cancer relative to normal tissue, with quantitative analysis of lymphatic vessel staining revealing a dramatic association between the incidence of ESAM positive tumour vessels and the presence of lymph node metastasis. <h3>Conclusion</h3> These findings reveal a remarkable degree of phenotypic plasticity in cancer lymphatics and provide new insight into the processes of lymphatic invasion and lymph node metastasis. The detailed characterisation of such qualitative changes may allow the development of better prognostic indicators in colorectal cancer and enlighten the search for improved anti-metastatic therapies.

Quantitative Investigation of Desmoplasia as a Prognostic Indicator in Colorectal Cancer

ABSTRACTBackground: The role of desmoplastic reaction (DR) in colorectal cancer invasion is still an open question. The presence of fibrous connective tissue may represent a barrier against cancer diffusion or a stroma to build up and support the tumor. Aims of the present study were to evaluate the influence of DR on long-term survival and to validate a reliable quantitative method to measure the desmoplastic tissue. Methods: This retrospective study included 86 patients who underwent radical colorectal resection for cancer, from a database of 429 patients. To achieve a quantitative histochemical measurement of DR, digital images were analyzed by a computerized image analysis program. DR was related to the overall survival and the quantitative method was related to the traditional one. Results: By using the Kaplan-Meier analysis, DR was found to be significantly associated with overall survival. Patients with a higher value of DR survived longer than those with smaller DR and the quantitative results were in accordance with those obtained by using the traditional methods. Conclusions: Desmoplasia seems to be a protective factor for survival in patients with colorectal carcinoma. The quantitative technique is easily standardized and can be routinely performed, so that DR may be a useful prognostic indicator. Notwithstanding, the conflicting outcomes reported in literature about DR need further biological and molecular studies to achieve definitive conclusions.

Expression status of S100A14 and S100A4 correlates with metastatic potential and clinical outcome in colorectal cancer after surgery

To investigate whether S100A14 and S100A4 expression correlates with metastatic potential and prognosis in colorectal cancer (CRC), we firstly used RT-PCR analysis to detect mRNA expression of S100A14 and S100A4 in 40 pairs of fresh tumor samples matched with adjacent normal tissues. We then evaluated the clinical significance of our findings with immunohistochemistry on 115 samples of formalin-fixed and paraffin-embedded tumors on tissue microarrays. Typically, we identified decreased S100A14 mRNA levels (52.5%, 21/40), and increased S100A4 mRNA levels (70.0%, 28/40) in primary CRC samples. In addition, down-regulated or absent S100A14 expression was detected in 56.5% of samples (65/115) and was correlated with poor differentiation (P=0.010). In contrast, overexpressed S100A4 was detected in 57.4% of samples (66/115) and was associated with lymph node metastasis (P=0.001). Simultaneous S100A14 low-expression and S100A4 high-expression was correlated with high CRC metastatic potential (P<0.001). Taken together, the signature derived from the combined expression status of S100A14 and S100A4 could be a valuable prognostic indicator in CRC.

Serum interleukin-6 levels in colorectal cancer patients—a summary of published results

It is now clear that inflammation and cancer initiation and progression are linked. Interleukin-6 (IL-6) is a pleiotropic inflammatory cytokine with described cancer stimulatory and also cancer inhibitory properties. The study's aim was to assess the potential of circulating IL-6 as a prognostic indicator in colorectal cancer. A literature search was conducted using PubMed, restricted to articles published in English language. We compared published results in regard to differences in IL-6 levels between healthy controls and colon cancer patients (seven published results), between patients with increasing tumor stages (eight published results), between patients with differences in tumor size (four published results), and between patients with and without liver (three published results) or lung metastasis (one published result). Furthermore, we reviewed the literature in regard to the possible correlation of IL-6 levels with survival time (five published results) and correlation of IL-6 levels and lymph node involvement (three published results). Concerning colon tumors, results are consistent. Colon cancer patients reveal higher serum IL-6 levels than healthy controls. Furthermore, higher IL-6 levels are associated with increasing tumor stages and tumor size, with metastasis and decreased survival. Therefore, circulating IL-6 might be prognostic indicator in colorectal cancer.

Perineural Invasion Is an Independent Predictor of Outcome in Colorectal Cancer

Perineural invasion (PNI) is associated with decreased survival in several malignancies, but its significance in colorectal cancer (CRC) remains to be clearly defined. We evaluated PNI as a potential prognostic indicator in CRC, focusing on its significance in node-negative patients. We identified 269 consecutive patients who had CRC resected at our institution. Tumors were re-reviewed for PNI by a pathologist blinded to the patients' outcomes. Overall and disease-free survivals were determined using the Kaplan-Meier method, with differences determined by multivariate analysis using the Cox multiple hazards model. Results were compared using the log-rank test. PNI was identified in less than 0.5% of the initial pathology reports. On rereview, 22% of tumors in our series were found to be PNI positive. The 5-year disease-free survival rate was four-fold greater for patients with PNI-negative tumors versus those with PNI-positive tumors (65% v 16%, respectively; P < .0001). The 5-year overall survival rate was 72% for PNI-negative tumors versus 25% for PNI-positive tumors. On multivariate analysis, PNI was an independent prognostic factor for both cancer-specific overall and disease-free survival. In a subset analysis comparing patients with node-negative disease with patients with stage III disease, the 5-year disease-free survival rate was 56% for stage III patients versus 29% for patients with node-negative, PNI-positive tumors (P = .0002). Similar results were seen for overall survival. PNI is grossly underreported in CRC and could serve as an independent prognostic factor of outcomes in these patients. PNI should be considered when stratifying CRC patients for adjuvant treatment.

PEA 3, a novel adverse indicator in colorectal cancer

PEA 3, a novel adverse indicator in colorectal cancer

Adherence to National Quality Forum (NQF) colorectal cancer indicators among members of the Florida Initiative for Quality Cancer Care (FIQCC) consortium

6563 Background: FIQCC is a consortium of 10 institutions participating in a comprehensive practice-based system of quality self-assessment across a number of cancer types. The NQF has endorsed several performance measures to assess the quality of care for colorectal cancer (CRC) patients. We have sought to identify adherence to NQF CRC indicators among members of FIQCC. Methods: Comprehensive chart reviews were conducted for all patients with CRC first seen in 2006 by a medical oncologist at one of the 10 FIQCC sites (2 academic/8 community). NQF quality measures included: 1) consideration or administration of chemotherapy to patients with stage III colon cancer (CC); 2) completeness of pathology reporting for CRC; 3) &gt;12 regional lymph nodes (LN) examined for resected CC. Statistical comparisons were performed using chi-squared analysis. Results: The population consisted of 475 patients (250 men and 225 women) with a median age of 65 years (range 27–92). Chemotherapy was considered/administered in 96.5% (136/141) of stage III CC patients. With respect to CRC pathologic reporting, there was strong compliance (&gt;90%) for reporting the number of LN examined and involved by tumor, proximal/distal margin status, depth of invasion, and histologic grade. However, only 225 of 295 (76.2%) reports documented lymphovascular invasion status. Radial margin status was included for 45% (27/60) of surgical rectal cancer specimens. Only 73.9% (173/234) of CC cases had &gt;12 LN examined. Of the NQF measures, significant differences across practice sites were noted for the reporting of histologic grade (p = 0.0002), proximal/distal margin status (p = 0.049), and lymphovascular invasion (p &lt; 0.0001). Conclusions: Although there was uniformly strong adherence to the application of adjuvant therapy for stage III CC across FIQCC sites, the adequacy of lymphadenectomy and LN examination for resected CC was lower and varied considerably across sites. There remains room for improvement of pathologic CRC reporting across the whole consortium as well as at individual sites. The FIQCC initiative allows for the identification of targets for global quality improvement as well as of specific measures for individual institutions. No significant financial relationships to disclose.

A platinum agent resistance gene, POLB, is a prognostic indicator in colorectal cancer

Recent progress in chemotherapy with platinum agents has improved clinical outcome in colorectal cancer (CRC), but there are no useful markers to predict the efficacy of such agents. DNA polymerase beta (POLB) mediates the efficacy of chemotherapy through DNA repair machinery. We analyzed the significance of POLB expression in CRC chemotherapy and its potential as a prognostic indicator. Using microarray, POLB was found to be overexpressed in CRC cells compared with corresponding normal colon epithelial cells. We determined the susceptibility of POLB-suppressed cells to cisplatin and oxaliplatin. We evaluated POLB mRNA expression in 97 CRC cases to determine the clinicopathologic significance of POLB expression. We found the suppression of POLB altered the in vitro susceptibility to cisplatin but not to oxaliplatin. In 97 CRC cases, lymph node metastasis, distant metastasis and TNM classification were significantly greater in the high POLB group than in the low group (P < 0.05). Patients with high POLB expression had significantly poorer prognosis than those with low expression (P < 0.05). The data indicate POLB is overexpressed in CRC cases with high malignant potential. We suggest POLB could be useful as a predictive marker for selection of patients responsive to cisplatin.

Prognostic and predictive factors in colorectal cancer

Prognostication of newly diagnosed colorectal cancer (CRC) predominantly relies on stage as defined by the UICC-TNM and American Joint Committee on Cancer classifications. Tumour extent, lymph node status, tumour grade...

PGC-1 expression level in human colorectal cancer: A predictor of lymph node metastasis

3616 Background: Previous study showed that the expression of peroxisome proliferator-activated receptor γ (PPARγ) and PPARγ coactivator-1 (PGC-1) was correlated with clinical outcome in breast cancer. However, no published data are available about the biological and clinical significance of PGC-1 in colorectal cancer. Thus, our aim was to explore the expression of PPARγ and PGC-1 in colorectal cancer as well as their association with other clinicopathological features, and to evaluate the role of PPARγ and PGC-1 as a prognostic indicator of colorectal cancer. Methods: We have investigated the presence of PPARγ and PGC-1 in human colorectal cancer tissues and adjacent normal tissues from 108 primary colorectal cancer patients by immunohistochemistry. The correlation between their expression and clinicopathologic features was investigated. Three-year overall survival of patients with different expression of PPARγ and PGC-1 were analyzed by the Kaplan-Meier method. Results: No significant correlation was found between PPARγ expression and age at surgery, gender, histopathologic differentiation, depth of infiltration, relapse, and Dukes’ stage. No significant correlation was found between PGC-1 expression and age at surgery, the histopathologic differentiation, the depth of infiltration, and relapse. However, PGC-1 expression was closely related to Duke’s stage and nodal metastasis (p=0.024 and p=0.020, respectively). Survival analysis showed that the PGC-1-positive group has a reduced overall survival (p=0.0367). Conclusions: Based on our results, PGC-1 may be valuable marker of nodal metastasis and represent a biomarker of poor prognosis in colorectal cancer. No significant financial relationships to disclose.

Stromal Staining for PINCH Is an Independent Prognostic Indicator in Colorectal Cancer

Particularly interesting new cysteine-histidine-rich protein (PINCH), a LIM domain adapter protein that functions in the integrin and growth factor signal transduction pathway, is upregulated in stroma associated with many common cancers. The finding suggested that PINCH may be involved in promoting tumor-stromal interactions that support tumor progression, and, if so, tumors with abundant PINCH stromal staining may have a worse prognosis. To test this hypothesis, 174 primary colorectal adenocarcinomas with 39 distant normal mucosa samples and 26 metastases in the lymph nodes were studied by immunohistochemistry, and 7 additional colon tumors were studied by Western blot analysis and immunofluorescence. The abundance of PINCH protein in stroma increased from normal mucosa to primary tumor to metastasis (P < .05), and was more intense at the invasive margin than it was in the intratumoral stroma. Strong stromal immunostaining for PINCH was shown to predict a worse outcome (rate ratio 2.1, 95% CI 1.16–3.37, P = .01), independent of Dukes stage, growth pattern, and tumor differentiation. PINCH was detected in fibroblasts, myofibroblasts, and a proportion of endothelial cells of the tumor vasculature, supporting the involvement of PINCH in promoting tumor-stromal interactions that support tumor progression. Interestingly, stromal staining for PINCH was an independent prognostic indicator in colorectal cancer.

Dynamic MRI in indirect estimation of microvessel density, histologic grade, and prognosis in colorectal adenocarcinomas

The relations of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters to microvessel density (MVD), histologic grade, and presence of metastasis were evaluated to establish new prognostic indicators in colorectal cancer (CRC). Fast-low angle shot DCE-MRI parameters (time-intensity curves, TICs; maximal relative enhancement within the first minute, E(max/1); maximal relative enhancement of the entire study, Emax; steepest slope of the contrast enhancement curve; and time to peak enhancement) of 21 CRCs (seven Duke stage B, 12 Duke stage C, and two Duke stage D) were retrospectively evaluated and correlated with corresponding postoperative MVD measurements, histologic grades, and presence of metastasis at 2 years. TICs were classified as type A in nine (43%), type B in seven (33%), and type C in five cases (24%). There was a significant difference between TIC types with regard to MVD (p < 0.05-0.001). Time to peak enhancement, steepest slope of TIC, and E(max/1) were strongly correlated with MVD (r = -0.765, p < 0.01; r = 0.681, p < 0.01; r = 0.634, p < 0.01; respectively). MVD, steepest slope of the enhancement curve, E(max/1), and Emax strongly correlated with histologic grade (r = 0.475, p < 0.05; r = 0.683, p < 0.01; r = 0.687, p < 0.01; r = 0.791, p < 0.01; respectively). There was a significant difference between groups of patients with and without metastasis with regard to histologic grade (p < 0.05) and two of the DCE-MRI parameters (p < 0.005 for E(max/1) and p < 0.05 for time to peak enhancement). Discriminant analysis correctly predicted the metastatic occurrence at 2 years in 90.5% of cases using E(max/1) (p < 0.001). Histologic grade resulted in lower rates of discrimination (66.7%; p < 0.05). DCE-MRI parameters may help in the prediction of MVD and histologic grade in CRC and may be used to predict therapeutic outcome.