Benign Colorectal Tumors Research Articles

Abstract B32: Longitudinal changes in plasma miRNA in patients with benign and malignant colorectal neoplasia

Abstract Introduction: The adenoma-carcinoma sequence is well-recognized as a stepwise pattern of mutational activation of oncogenes and inactivation of tumor suppressor genes resulting in sporadic colorectal cancer (CRC) development from colorectal adenomas (CRA) within the chromosomal instability pathway. MicroRNAs (miRNA) play an important role in oncogenesis by regulating gene expression and are known to be actively released from cells. They are found in body fluids such as plasma, saliva, feces and urine. We have previously demonstrated differential expression of plasma miRNAs in patients with CRC as compared to that of controls. Methods: Plasma was isolated from 10 patients: 5 patients with advanced colorectal adenoma (>0.6cm diameter) and 5 patients with stage II or III colorectal cancer prior to treatment and 4-6 weeks following endoscopic removal or surgical resection, respectively. RNA was extracted from plasma (Qiagen® miRNeasy), RT-PCR performed and 768 miRNAs were screened using microfluidic array technology (Applied BioSystems®) in pre- and post-treatment samples for each patient. Data were analyzed using paired t-tests after normalizing raw cycle threshold data to endogenous RNU6 for pre- and post-treatment samples. In addition, miRNA expression data from both pre- and post-treatment CRA and CRC samples were compared to that of plasma from 10 individuals without neoplasia (controls) (ANOVA). Results: Significant differential expression of plasma miRNAs was observed between pre- and post-treatment samples in both CRA and CRC groups. Interestingly, there was generalized miRNA upregulation in CRA when comparing pre-treatment samples to post-treatment samples. Conversely there was miRNA down-regulation in pre-treatment CRC plasma as compared to post-resection samples. Utilizing significantly dysregulated miRNAs, as well as p-values, AUC, fold-change and biological significance, miRNA panels were selected to facilitate detection of CRA recurrence (following complex polypectomy for large polyps) or for detection of recurrent CRC following resection. The resulting panel was able to differentiate between pre- and post-treatment samples for CRA (miR-186 and miR-623) with AUC 0.94 (95% CI 0.76 – 1.00) and for CRC (miR-324-5p, miR-30d and miR-766) with AUC 0.88 (95% CI 0.63 – 1.00). In addition, while miRNA expression of pre-treatment CRA and CRC samples differed significantly from controls, post-treatment CRA and CRC samples did not. Conclusion: Comparison of pre- and post-treatment plasma samples reveals differing patterns of changes in miRNA expression in benign colorectal neoplasms (CRA) as opposed to invasive neoplasia (CRC). The observed miRNA down-regulation prior to surgical resection of CRC might indicate decreased expression of miRNAs inhibiting oncogenes prior to cancer treatment, while the miRNA upregulation seen in pre-treatment CRA plasma could indicate inhibition of tumor suppressors. Such observations will perhaps elucidate the role of miRNA in carcinogenesis and may provide for a relatively non-invasive method of detecting such lesions. Further validation is needed to develop a miRNA panel that will allow monitoring for evidence of recurrent disease. Citation Format: Jane Carter, Vanessa States, Uri Netz, Jianmin Pan, Shesh Rai, Susan Galandiuk. Longitudinal changes in plasma miRNA in patients with benign and malignant colorectal neoplasia. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr B32.

A novel mixed integer programming for multi-biomarker panel identification by distinguishing malignant from benign colorectal tumors

Multi-biomarker panels can capture the nonlinear synergy among biomarkers and they are important to aid in the early diagnosis and ultimately battle complex diseases. However, identification of these multi-biomarker panels from case and control data is challenging. For example, the exhaustive search method is computationally infeasible when the data dimension is high. Here, we propose a novel method, MILP_k, to identify serum-based multi-biomarker panel to distinguish colorectal cancers (CRC) from benign colorectal tumors. Specifically, the multi-biomarker panel detection problem is modeled by a mixed integer programming to maximize the classification accuracy. Then we measured the serum profiling data for 101 CRC patients and 95 benign patients. The 61 biomarkers were analyzed individually and further their combinations by our method.We discovered 4 biomarkers as the optimal small multi-biomarker panel, including known CRC biomarkers CEA and IL-10 as well as novel biomarkers IMA and NSE. This multi-biomarker panel obtains leave-one-out cross-validation (LOOCV) accuracy to 0.7857 by nearest centroid classifier. An independent test of this panel by support vector machine (SVM) with threefold cross validation gets an AUC 0.8438. This greatly improves the predictive accuracy by 20% over the single best biomarker. Further extension of this 4-biomarker panel to a larger 13-biomarker panel improves the LOOCV to 0.8673 with independent AUC 0.8437. Comparison with the exhaustive search method shows that our method dramatically reduces the searching time by 1000-fold. Experiments on the early cancer stage samples reveal two panel of biomarkers and show promising accuracy.The proposed method allows us to select the subset of biomarkers with best accuracy to distinguish case and control samples given the number of selected biomarkers. Both receiver operating characteristic curve and precision-recall curve show our method’s consistent performance gain in accuracy. Our method also shows its advantage in capturing synergy among selected biomarkers. The multi-biomarker panel far outperforms the simple combination of best single features. Close investigation of the multi-biomarker panel illustrates that our method possesses the ability to remove redundancy and reveals complementary biomarker combinations. In addition, our method is efficient and can select multi-biomarker panel with more than 5 biomarkers, for which the exhaustive methods fail.In conclusion, we propose a promising model to improve the clinical data interpretability and to serve as a useful tool for other complex disease studies. Our small multi-biomarker panel, CEA, IL-10, IMA, and NSE, may provide insights on the disease status of colorectal diseases.The implementation of our method in MATLAB is available via the website: http://doc.aporc.org/wiki/MILP_k.

Sa1615 Outcomes of Surgical Resection for Benign Colorectal Neoplasms: an Analysis of 359 Resections At a Single Academic Medical Center

Despite the efficacy of endoscopic resection (ER), patients may undergo surgery for complex benign colorectal neoplasms (“complex polyps”), either after failed ER or as primary therapy. There is scant data on surgical outcomes for complex polyps to aid physicians in appropriately counseling patients on management options. Aims: To evaluate the 1) length of stay (LOS) and hospital charges; 2) adverse event (AE) rates; and 3) AE risk factors in patients undergoing surgery for complex colon polyps.

Assay reproducibility in clinical studies of plasma miRNA.

There are increasing reports of plasma miRNAs as biomarkers of human disease but few standards in methodologic reporting, leading to inconsistent data. We systematically reviewed plasma miRNA studies published between July 2013-June 2014 to assess methodology. Six parameters were investigated: time to plasma extraction, methods of RNA extraction, type of miRNA, quantification, cycle threshold (Ct) setting, and methods of statistical analysis. We compared these data with a proposed standard methodologic technique. Beginning with initial screening for 380 miRNAs using microfluidic array technology and validation in an additional cohort of patients, we compared 11 miRNAs that exhibited differential expression between 16 patients with benign colorectal neoplasms (advanced adenomas) and 16 patients without any neoplasm (controls). Plasma was isolated immediately, 12, 24, 48, or 72 h following phlebotomy. miRNA was extracted using two different techniques (Trizol LS with pre-amplification or modified miRNeasy). We performed Taqman-based RT-PCR assays for the 11 miRNAs with subsequent analyses using a variable Ct setting or a fixed Ct set at 0.01, 0.03, 0.05, or 0.5. Assays were performed in duplicate by two different operators. RNU6 was the internal reference. Systematic review yielded 74 manuscripts meeting inclusion criteria. One manuscript (1.4%) documented all 6 methodological parameters, while < 5% of studies listed Ct setting. In our proposed standard technique, plasma extraction ≤12 h provided consistent ΔCt. miRNeasy extraction yielded higher miRNA concentrations and fewer non-expressed miRNAs compared to Trizol LS (1/704 miRNAs [0.14%] vs 109/704 miRNAs [15%], not expressed, respectively). A fixed Ct bar setting of 0.03 yielded the most reproducible data, provided that <10% miRNA were non-expressed. There was no significant intra-operator variability. There was significant inter-operator variation using Trizol LS extraction, while this was negligible using modified miRNeasy. For standardized reporting, we recommend plasma extraction ≤ 12 h, using modified miRNeasy extraction and utilizing a 0.03 Ct.

PTEN expression in colorectal adenomas: Relationship to morphology and cell heterogeneity

IntroductionColorectal adenomas are the most frequent benign colorectal tumors. These tumors are characterized by dysplasia, low and high grade, the latter having the potential to evolve to adenocarcinoma.The aim of this study was to study the expression patterns of PTEN protein in a series of colorectal adenomas and the relationships to cell proliferation and CD133, marker of stem phenotype. MethodsColorectal adenomas were studied for the immunohistochemical expression of PTEN on tissue microarrays. PTEN expression was analysed with regard to morphological features and with regard to the Ki67 and CD133-positive cell compartments by using the Kendall rank-correlation test. ResultsPTEN was expressed in 92% adenomas, either in a cytoplasmic or nuclear pattern. Cytoplasmic PTEN was correlated to cytoplasmic CD133 (p=0.02, tau 0.191) while nuclear PTEN to decreased adenoma size and to tubular architecture (p=0.01, τ−0.184 and p=0.01, τ−0.183). Nuclear PTEN was also correlated to low grade intraepithelial neoplasia, while global PTEN (nuclear or cytoplasmic) was correlated to the presence of a decreased Ki67-positive component but with marginal significance (p=0.06, τ−0.144 and p=0.07, τ−0.213). ConclusionThe results of this study suggest a role for PTEN in colorectal adenoma morphogenesis and cell protein heterogeneity, being correlated to decreased size, tubular architecture and a high CD133-positive component.

Risk of developing colorectal cancer and benign colorectal neoplasm in patients with chronic constipation.

Chronic constipation (CC) is a highly prevalent health problem, potentially associated with increased risk of colorectal cancer (CRCancer). To investigate the association between CC, its severity, and CRCancer by estimating the relative risk of developing CRCancer and benign colorectal neoplasm (BCN) among severity-stratified patients with and without CC. Chronic constipation patients from a large retrospective US claims database were matched 1:3 with CC-free controls by demographic characteristics. CRCancer and BCN prevalence were measured over 1 year. In pre-index CRCancer- and BCN-free patients, incidence rate ratios (IRRs) of new CRCancer and BCN were calculated. Multivariate regression models adjusted for comorbidities and family history. CC patients' disease severity was rated based on CC-related resource use. IRRs for new CRCancer and BCN were estimated for CC severity groups and controls. Chronic constipation (N = 28,854) and CC-free (N = 86,562) patients had mean age 61.9 years; 66.7% were female. One-year CRCancer prevalence was 2.7% and 1.7%, and BCN prevalence was 24.8% and 11.9% for CC and CC-free patients, respectively. Adjusted IRRs between CC and CC-free patients were 1.59 [95% confidence interval (CI): 1.43-1.78] and 2.60 [95% CI: 1.51-2.70] for CRCancer and BCN, respectively. Patients with severe and very severe CC had significantly greater incidence of CRCancer and BCN. At ≥ 2 and ≥ 5 years of observation, CRCancer and BCN incidence remained consistently and significantly higher for CC patients. Patients with chronic constipation are associated with significantly higher prevalence and incidence of colorectal cancer and benign colorectal neoplasm than matched chronic constipation-free patients. These risks increase with the severity of chronic constipation.

Tu1449 Colonic Endoscopic Mucosal Resection of Giant (≥4 CM) Colorectal Lesions: Longitudinal Outcomes of a US Endoscopy Unit

In the US, the mean size of benign colorectal lesions referred for surgery is 2 cm. Favorable outcomes of endoscopic resection for the removal of benign colorectal neoplasms have been shown. Endoscopic outcomes from the US, however, have been limited, particularly on large lesions. We aimed to assess the safety and efficacy of the endoscopic resection of giant (≥4 cm) colorectal lesions.

Whole‐genome methylation analysis of benign and malignant colorectal tumours. J Pathol 2013; 229: 697–704

Whole‐genome methylation analysis of benign and malignant colorectal tumours. <i>J Pathol</i> 2013; 229: 697–704

Management of the malignant colorectal polyp: ACPGBI position statement

*Royal Wolverhampton Hospitals NHS Trust, Wolverhampton, UK, †Torbay Hospital, Torquay, UK, ‡Department of General Surgery, Manchester Royal Infirmary, Manchester, UK, §Royal Infirmary, Glasgow, UK, ¶Department of Histopathology, Royal Bolton NHS Foundation Trust, Bolton, UK, **Imperial College Healthcare NHS Trust, Charing Cross Hospital, London, UK, ††The Royal Marsden Hospital, London, UK, ‡‡Salisbury NHS Foundation Trust, Salisbury, UK and §§Department of Histopathology, University Hospital of South Manchester, Manchester, UK

Histopathology Analysis of Benign Colorectal Diseases and Colorectal Cancer in Hatyai Hospital, Songkhla, Thailand

Colorectal cancer (CRC) is a major cause of morbidity and mortality in the western world and also ranks as the fifth-leading malignancy and death in Thailand. This study aimed to provide a present outlook of colorectal diseases among Thai patients with special emphasis on CRC in Hatyai, Songkhla, southern Thailand. This retrospective study covered ten year data of CRC, benign colorectal tumors and non-colorectal tumors from the Department of Pathology in Hatyai Hospital, Songkhla, Thailand, between years 2003-2012. Incidence rates based on age, gender, ten year incidence trends, and distribution of histopathological characteristics of patients were calculated and demonstrated. Out of 730 biopsies, 100 cases were benign colorectal tumors, 336 were CRC and 294 were non-colorectal tumors. Colorectal tumors (both benign and CRC) (60.1%) were more common than non-colorectal tumors (39.9%). CRC (77.1%) were more common than benign colorectal tumors (32.9%). Colorectal tumors were mainly found in patients aged over sixty whereas non-colorectal and benign colorectal tumors were found in those under sixty (P=0.01). sAmong CRC, adenocarcinoma contributed about 97.3% of all cases with well differentiated tumors being the most frequent (56.9%). Both benign colorectal tumors and CRC were more commonly found in males (63%) than females (37%). The incidence trend of CRC demonstrated increase from 2003-2012. The incidence of CRC increased in Hatyai from 2003-2012. CRC tends to be more common in people older than sixty, thus, screening programs, cost-effective analysis of treatment modalities, and treatment protocols for the elderly should be examined. Proper implementation of preventive measures such as changing lifestyle factors might enhance control of colorectal disease.

Laparoscopic-Facilitated Endoscopic Submucosal Dissection, Mucosal Resection, and Partial Circumferential (“Wedge”) Colon Wall Resection for Benign Colorectal Neoplasms That Come to Surgery

Large polyps that come to surgery are removed via colectomy (CR). Alternatives are MIS-facilitated endoscopic submucosal dissection/endoscopic mucosal resection (ESD/EMR) or wedge resection (WR). This study presents the results of 26 polyp patients who had minimally invasive surgery (MIS)-monitored ESD/EMR, WR, or if necessary, standard CR. The authors used a retrospective review of 1 surgeon's experience. ESD/EMR was the first choice, WR was the second, and CR was the last resort. Polyp locations were as follows: right/transverse, 16 (62%); rectum, 7 (27%); and left/sigmoid, 3 (12%). ESD/EMR was successful in 13 patients and WR in 4; 9 patients required CR. Median flatus times were as follows: ESD/EMR, 1 day; WR, 2 days; and CR, 3 days (ESD/EMR vs CR, P = .01). Median length of stay was as follows: ESD/EMR, 3 days; WR, 5 days; and CR, 5 days (ESD/EMR vs CR, P = .0037). There were no leaks or abscesses. Carcinoma was found in 3 patients. Postoperatively, 2 ESD/EMR patients had residual polyp fully removed via a scope. ESD/EMR and WR appear to be safe but techniques are evolving. Larger studies are needed.

Differentiating malignant colorectal tumor patients from benign colorectal tumor patients by assaying morning urinary arylsulfatase activity

For several decades urinary arylsulfatase (ARS) activity has been reported to be elevated in many cancers. It has been shown that urinary ARS activity may serve as a marker of tumor progression and therapy surveillance. This study was designed to evaluate the clinical application of detection of urinary ARS activity. We used a modified precipitation method to separate ARS from urine samples. This method was easy to use and applicable for a high throughput assay. We tested and analyzed the morning urinary ARS activity in 300 normal controls, 97 patients with benign tumors and 119 with malignant colorectal tumor. Compared to normal male and female controls, morning urinary ARS activity was significantly higher in malignant colorectal tumor patients. Moreover, morning urinary ARS activity had a relatively high efficacy in distinguishing patients with malignant colorectal tumors from those with benign colorectal tumors. The area under the curve in the receiver operator characteristics curve analysis was 0.89 (95% CI, 0.83-0.95) and 0.87 (95% CI, 0.79-0.94) in male and female colorectal patients, respectively. These data suggest the potential application of morning urinary ARS activity to conventional clinical use.

Intussuscepting Rectal Lipoma: A Case Report and Review of Literature

Lipomas are the second most common benign colorectal neoplasm. Rectallipomas are rare compared to colonic lipomas, with less than 15 cases described. In contrast to colonic lipomas which are usually asymptomatic, most of the rectal lipomas are symptomatic. We present here our patient with symptomatic rectal Lipoma and review the limited data available in the current surgical literature.

Laparoscopic colorectal resection for benign polyps not suitable for endoscopic polypectomy

Endoscopic polypectomy still remains the cornerstone of therapy for colorectal polyps and adenomas. However, if colorectal polyps are too large or not accessible for endoscopic ablation or cannot be removed without an increased risk for perforation, operative procedures are required. In such circumstances, laparoscopic resection represents a minimally invasive alternative. Between January 1993 and December 2004, more than 2,500 endoscopic polypectomies were performed at the Department of Surgery, University of Schleswig-Holstein, Campus Lübeck, Germany. In patients which could not be treated by endoscopic polypectomy due to size, location, and/or risk of complications, a laparoscopic colorectal resection was performed. All data were prospectively assessed in our "colorectal resection" database. The database analysis revealed 58 patients with endoscopically not resectable colorectal polyps who underwent a laparoscopic colorectal resection (intend to treat). In 54 patients, the operative procedure could be finished by the laparoscopic approach (study population). The conversion rate was 6.9% (four of 58). An ileocolic resection was performed in 20 patients (37.0%), and 14 patients (25.9%) underwent an anterior rectal resection. A right colectomy was necessary in 12 patients (22.2%), and six patients (11.1%) underwent a sigmoid resection. In the remaining two patients, a left colectomy and a resection of the transverse colon were performed. Intra- and postoperative complications occurred in five patients (9.3%). Perioperative mortality was not registered. The histopathological work-up revealed benign disease in all cases. Laparoscopic resection of colorectal polyps is a safe and minimally invasive technique for the management of benign colorectal tumors. Thus, the laparoscopic approach to endoscopically not resectable polyps enriches the therapeutic spectrum.

Nutritional and antioxidant status of colorectal tumor patients

Oxidative stress is one of the risk factors of colorectal carcinogenesis. In inflammatory reactions the activated leucocytes product mutagenic and mitogenic free radicals, hereby promoting tumor formation. Obesity, hyperlipidemia and hyperinsulinemia increases the energy supply of epithelial cells, thus leads to deregulation of mitochondrial electron transport chain. The latter leads to increased free radical production that causes troubles in cell cycle regulation, mutations, and unrestricted proliferation of damaged cells. Evaluation of some parameters of antioxidant and nutritional status in patients with benign or malignant colorectal neoplasm. Assessment of nutrient intake, measurement of some anthropometric parameters (body height, body weight, waist, hip and arm circumference, waist/hip ratio), determination of serum prealbumin level, evaluation of the biomarkers of antioxidant status (superoxide dismutase and glutathione peroxidase activity, levels of uric acid and albumin, total antioxidant status, free radical scavenger capacity), determination the concentration of oxidated product and malondialdehyde. In patients with malignant tumor the dietary fiber, folate and vitamin A intake was under the optimal level, and the serum prealbumin concentration was lower than in patients with benign lesion. There was a high incidence of overweight and obesity among patients. Significant difference was found between diseased subjects and healthy controls in terms of the biomarkers of antioxidant status, such as free radical scavenger capacity, concentration of advanced oxidation protein products and malondialdehyde, glutathione peroxidase activity. The insufficient folate and vitamin A intake, the high incidence of overweight and obesity, and the abnormal values of the biomarkers of antioxidant status observed in the study groups seem to support the correlation between colorectal tumor, nutritional and antioxidant status.

The localization of an anti-tumour monoclonal antibody (791T/36) in gastrointestinal tumours.

Fifty-six patients with gastrointestinal cancers and four patients with benign colorectal tumours have been injected with radiolabelled anti-tumour monoclonal antibody ( 791T /36) to assess the degree of localization of the antibody by external scintiscanning and measurements on resected specimens. Twenty-nine patients with primary colorectal cancer showed increased uptake of the radiolabelled antibody in the resected tumours, with a tumour to normal tissue (T:NT) ratio of 2.5:1. All but two of fifteen patients with recurrent or metastatic tumour showed positive images of the deposits on external scintiscanning. Twelve patients with noncolonic gastrointestinal malignancy were studied and in only two patients were tumours demonstrated by external scanning. There were no positive images in four patients with benign colonic disease nor could increased uptake of radiolabelled antibody be demonstrated in the resected specimens. Immunohistology and autoradiography have shown that the antibody can be demonstrated in the pseudoacini and stroma of colon cancer. There are indications that this may represent localization to a cell surface antigen which becomes detached in the processing of the histological sections. It seems that in the gastrointestinal tract the monoclonal antibody 791T /36 is consistently taken up by colorectal cancer. Only a few noncolonic cancers and no benign colonic tumours take up the antibody. This antibody uptake may prove of value in the detection of occult metastases and in the targeting of antitumour agents.

Bile acid receptors in colorectal cancer.

Bile acids are thought to be involved in both the aetiology and development of colorectal cancer. In this study the existence of specific bile acid receptor proteins has been postulated. A receptor assay which involved labelling with 14C-deoxycholic acid was performed as well as autoradiography using 3H-deoxycholic acid. In an initial study resected colorectal cancer and adjacent histologically normal colorectal mucosa from 39 patients were studied, as were samples of normal gastric mucosa, cancers and benign colorectal tumours. Specific receptors to deoxycholic acid were detected in 12 (30.8 per cent) of the colorectal cancers, but in only 1 (2.6 per cent) of the samples from normal colorectal mucosa (X2 = 11.16, P less than 0.005). No deoxycholic acid receptors were detected in any other tissue studied. Autoradiographs of colorectal cancers showed binding of 3H-deoxycholic acid in receptor-positive tumour tissue. These findings might provide some explanation for the evidence linking bile acids with the disease.

Inhibition of experimental colorectal cancer by razoxane (ICRF-159).

Large bowel cancer induced in rats by dimethylhydrazine (DMH) closely resembles human disease both histologically and clinically. In this study it has been used to assess the antimitotic drug razoxane (ICRF-159). Dimethylhydrazine induced benign colorectal tumours after 20 weeks and adenocarcinomas from 30 weeks. Razoxane was given from week 25 until the end of experiment (week 35) to see if this drug could inhibit the development of tumours. Animals were randomly allocated to four groups: DMH + razoxane (26), DMH + control (26), control + razoxane (25), control + control (25). There were fewer malignant colorectal tumours in rats receiving razoxane than in the controls (10 vs. 24; P = 0.04). Some animals developed malignant tumours of the small intestine as well as the large bowel and the number of malignant tumours for the whole intestinal tract was also reduced in animals receiving razoxane (15 vs. 32; P = 0.025). This study demonstrates inhibition of the development of malignant tumours in rats by razoxane. This finding may have relevance to colorectal cancer in man where razoxane has been used in disseminated disease and as an adjuvant to surgery.

Low expression of XIAP‐associated factor 1 in human colorectal cancers

Eight cellular homologs of the inhibitors-of-apoptosis proteins (IAP) have been identified in humans and of them, the X-linked IAP (XIAP) is the most potent. XIAP-associated factor 1 (XAF1) is a newly discovered XIAP-binding protein that negatively regulates the caspase-inhibiting activity of XIAP. It is either not expressed or present at extremely low levels in many cancer cell lines. The aims of the present study were: (i) to investigate the expression of XAF1 in human colorectal cancers (CRC) both in vitro and in vivo, and (ii) to evaluate the possibility of XAF1 as a new tumor marker. The expression of XAF1 in four human colon cancer cell lines (Colo205, Colo320, SW1116, LoVo) and in samples from 70 patients with CRC was analyzed by reverse transcriptase-polymerase chain reaction. XAF1 concentrations were also detected in the peripheral circulation of the 70 patients, as well as three traditional circulating cancer-associated antigens. A low concentration of XAF1 mRNA was detectable in the three colon cancer cell lines other than Colo205, which showed the strongest expression of XAF1. The expression of XAF1 in tissue was relatively lower in primary CRC compared with a relatively higher level in benign colorectal tumors (P < 0.01). Although the XAF1 expression in circulation of those with CRC was also lower than in those with benign tumors, there was no statistical significance (P > 0.05). The present results suggest that the low expression of XAF1 in tumor tissue coincides with a similar level in the peripheral circulation, which contributes at least part to the malignant behavior of CRC. Integrating the XAF1 relative expression value with the other three traditional tumor biomarkers created a four-parameter assay that significantly improved the rate of diagnosis of CRC.

A phosphatase associated with metastasis of colorectal cancer.

To gain insights into the molecular basis for metastasis, we compared the global gene expression profile of metastatic colorectal cancer with that of primary cancers, benign colorectal tumors, and normal colorectal epithelium. Among the genes identified, the PRL-3 protein tyrosine phosphatase gene was of particular interest. It was expressed at high levels in each of 18 cancer metastases studied but at lower levels in nonmetastatic tumors and normal colorectal epithelium. In 3 of 12 metastases examined, multiple copies of the PRL-3 gene were found within a small amplicon located at chromosome 8q24.3. These data suggest that the PRL-3 gene is important for colorectal cancer metastasis and provide a new therapeutic target for these intractable lesions.