Early Detection Of Colorectal Carcinoma Research Articles

A 5-Hydroxymethylcytosine-Based Noninvasive Model for Early Detection of Colorectal Carcinomas and Advanced Adenomas: The METHOD-2 Study.

Detection of colorectal carcinomas at a time when there are more treatment options is associated with better outcomes. This prospective case-control study assessed the 5-hydroxymethylcytosine (5hmC) biomarkers in circulating cell-free DNA (cfDNA) for early detection of colorectal carcinoma and advanced adenomas (AA). Plasma cfDNA samples from 2,576 study participants from the multicenter METHOD-2 study (NCT03676075) were collected, comprising patients with newly diagnosed colorectal carcinoma (n = 1,074), AA (n = 356), other solid tumors (n = 80), and non-colorectal carcinoma/AA controls (n = 1,066), followed by genome-wide 5hmC profiling using the 5hmC-Seal technique and the next-generation sequencing. A weighted diagnostic model for colorectal carcinoma (stage I-III) and AA was developed using the elastic net regularization in a discovery set and validated in independent samples. Distribution of 5hmC in cfDNA reflected gene regulatory relevance and tissue of origin. Besides being confirmed in internal validation, a 96-gene model achieved an area under the curve (AUC) of 90.7% for distinguishing stage I-III colorectal carcinoma from controls in 321 samples from multiple centers for external validation, regardless of primary location or mutation status. This model also showed cancer-type specificity as well as high capacity for distinguishing AA from controls with an AUC of 78.6%. Functionally, differential 5hmC features associated with colorectal carcinoma and AA demonstrated relevance to colorectal carcinoma biology, including pathways such as calcium and MAPK signaling. Genome-wide mapping of 5hmC in cfDNA shows promise as a highly sensitive and specific noninvasive blood test to be integrated into screening programs for improving early detection of colorectal carcinoma and high-risk AA.

A Young Woman with High-Grade Rectosigmoid Adenocarcinoma, no Other Specified, T2n2aM0: A Case Report and Literature Review

BACKGROUND: Colorectal cancer (CRC) is the fourth most common cancer in which the majority of CRCs are diagnosed between the ages of 50 and 70 years. Based on current trends, the incidence of colon and rectal cancers can increase by 124% in people aged 35–49 years and at the age of 20–34 will increase by 28% and 46%. OBJECTIVES: To report a case of a 24-year-old female patient with CRC. CASE REPORT: A 24-year-old female patient came to the Emergency Room at Bendan Hospital, Pekalongan City, with complaints of bleeding since 1 year ago. There are complaints in the past 6 months; the patient’s weight has decreased by up to 20 kg. Rectal toucher examination revealed normal (+) anal sphincter tone, a palpable mass in the anal canal, and was fragile; there were feces and blood in gloves. Abdominal ultrasonography found a solid tumor mass in the rectum area with a volume of 181 cc, suggesting a malignancy of the rectum. During a colonoscopy, a circular, fragile, and easily bleeding tumor was found, approximately 1 cm from the anal verge, and then biopsy was performed. Histopathological examination of the colon biopsy suggests a well-differentiated, rectosigmoid, NOS adenocarcinoma. The patient then underwent surgery using the Miles procedure technique. The patient’s condition after the operation improved, so after a week of treatment, the patient was able to undergo outpatient treatment. CONCLUSION: A complete history, physical examination, and supporting investigation are very useful in early detection of colorectal carcinoma, especially in young patients.

Types of colorectal cancer and dysplasia associated with inflammatory bowel disease

Ulcerative colitis (UC) and Crohn’s disease (CD) are two major inflammatory disorders of the intestinal wall collectively known as inflammatory bowel disease (IBD). Colorectal carcinoma (CRC) is the most significant and grave consequence of IBD and is preceded by dysplasia in majority of the cases. In this review we aim to discuss the various types of dysplasia found in patients with CRC due to IBD. A thorough literature search was conducted in online databases such as PubMed, Google Scholar, from which all studies published in the last ten years were included in this review. The major development in diagnostic procedures and visualization modalities have aided our understanding of dysplasia, which is now known to be the strongest predictor and marker for CRC development. However, the unpredictable behavior and progression of dysplasia still warrants vigilant surveillance. Dysplasia has been classified on histological characteristics using grades of dysplasia from ‘negative for dysplasia’ to ‘high grade dysplasia’. On visibility via an endoscope from ‘visible dysplasia’ to ‘invisible dysplasia’ and macroscopic features of ‘conventional dysplasia’ and ‘non-conventional dysplasia’. No single classification can be utilized to define the stage of dysplasia and more importantly predict its progression and outcome of CRC. Using evidence-based medicine an integrated classification expanding on a management algorithm must be formulated by a panel of experts to steer management of the disease. A multidisciplinary, tailored approach with a strong emphasis on regular and timely surveillance to ensure early detection of CRC can enhance quality of life and patient outcomes.

Relation between expression of hMLH1 and p53 mRNA genes, in the feces of patients with colorectal carcinoma. Cross-sectional study

Colorectal carcinoma (CRC) is one of the main public health problems. The mortality of CRC is about 8%. Early detection of CRC is very important to prevent death because this cancer could be cured through surgery if the diagnosis can be made as early as possible. Therefore screening strategy for early detection of CRC is critical in reducing mortality. Many investigations supporting the detection of CRC have been developed, including the fecal DNA mutation test using advanced cytological techniques. It is capable of assessing colonocytes for the presence of DNA, RNA, and protein as molecular biomarkers of neoplasia in CRC, including p53 and hMLH1. This study implemented observational approach with a cross-sectional study of the feces of patients with CRC regardless of the stage and grade. The purpose of this study was to determine the expression of the hMLH1 and p53 mRNA genes in the feces of 48 patients with CRC from two hospitals in Indonesia, Siloam Hospitals in Cikarang and Dr. Wahidin Sudirohusodo Hospital in Makassar. The results showed that all adenocarcinoma feces samples with various tumor stages and grades had excess mRNA expression (more than twice the normal amount in Fold Change units) for both the hMLH1 and p53 genes. The average expression of the hMLH1 mRNA gene was the highest at stage two and grade one, while the lowest was at stage four and grade three. In contrast, the average p53 mRNA gene expression was the highest at stage four and grade three, while the lowest was at stage two and grade one. The study suggested that there was a relation between and the expression of hMLH1 and p53 mRNA gene. We concluded that while both hMLH1 and p53 genes in patients’ feces with CRC were overexpressed, they did not significantly affect the grade of CRC.

Computational learning of features for automated colonic polyp classification

Shape, texture, and color are critical features for assessing the degree of dysplasia in colonic polyps. A comprehensive analysis of these features is presented in this paper. Shape features are extracted using generic Fourier descriptor. The nonsubsampled contourlet transform is used as texture and color feature descriptor, with different combinations of filters. Analysis of variance (ANOVA) is applied to measure statistical significance of the contribution of different descriptors between two colonic polyps: non-neoplastic and neoplastic. Final descriptors selected after ANOVA are optimized using the fuzzy entropy-based feature ranking algorithm. Finally, classification is performed using Least Square Support Vector Machine and Multi-layer Perceptron with five-fold cross-validation to avoid overfitting. Evaluation of our analytical approach using two datasets suggested that the feature descriptors could efficiently designate a colonic polyp, which subsequently can help the early detection of colorectal carcinoma. Based on the comparison with four deep learning models, we demonstrate that the proposed approach out-performs the existing feature-based methods of colonic polyp identification.

Discovery and validation of methylation signatures in blood-based circulating tumor cell-free DNA in early detection of colorectal carcinoma: a case\u2013control study

BackgroundEarly detection of colorectal carcinoma (CRC) would help to identify tumors when curative treatments are available and beneficial. However, current screening methods for CRC, e.g., colonoscopy, may affect patients’ compliance due to the uncomfortable, invasive and time-consuming process. In recent decades, methylation profiles of blood-based circulating tumor DNA (ctDNA) have shown promising results in the early detection of multiple tumors. Here we conducted a study to investigate the performance of ctDNA methylation markers in early detection of CRC.ResultsIn total, 742 participants were enrolled in the study including CRC (n = 332), healthy control (n = 333), benign colorectal disease (n = 65) and advanced adenoma (n = 12). After age-matched and randomization, 298 participants (149 cancer and 149 healthy control) were included in training set and 141 (67 cancer and 74 healthy control) were in test set. In the training set, the specificity was 89.3% (83.2–93.7%) and the sensitivity was 88.6% (82.4–93.2%). In terms of different stages, the sensitivities were 79.4% (62.1–91.2%) in patients with stage I, 88.9% (77.3–95.8%) in patients with stage II, 91.4% (76.9–98.2%) in patients with stage III and 96.2% (80.3–99.9%) in patients with stage IV. Similar results were validated in the test set with the specificity of 91.9% (83.1–97.0%) and sensitivity of 83.6% (72.5–91.6%). Sensitivities for stage I-III were 87.0% (79.7–92.4%) in the training set and 82.5% (70.2–91.3%) in the test set, respectively. In the unmatched total population, the positive ratios were 7.8% (5.2–11.2%) in healthy control, 30.8% (19.9–43.5%) in benign colorectal disease and 58.3% (27.5–84.7%) in advanced adenoma, while the sensitivities of stage I–IV were similar with training and test sets. Compared with methylated SEPT9 model, the present model had higher sensitivity (87.0% [81.8–91.2%] versus 41.2% [34.6–48.1%], P < 0.001) under comparable specificity (90.1% [85.4–93.7%] versus 90.6% [86.0–94.1%]).ConclusionsTogether our findings showed that ctDNA methylation markers were promising in the early detection of CRC. Further validation of this model is warranted in prospective studies.

Genome-wide DNA methylation profiles of low- and high-grade adenoma reveals potential biomarkers for early detection of colorectal carcinoma

BackgroundAbnormal DNA methylation is a hallmark of human cancers and may be a promising biomarker for early diagnosis of human cancers. However, the majority of DNA methylation biomarkers that have been identified are based on the hypothesis that early differential methylation regions (DMRs) are maintained throughout carcinogenesis and could be detected at all stages of cancer.MethodsIn this study, we identified potential early biomarkers of colorectal cancer (CRC) development by genome-wide DNA methylation assay (Illumina infinium450, 450 K) of normal (N = 20) and pre-colorectal cancer samples including 18 low-grade adenoma (LGA) and 22 high-grade adenoma (HGA), integrated with GEO and ArrayExpress datasets (N = 833).ResultsWe identified 209 and 8692 CpG sites that were significantly hyper-methylated in LGA and HGA, respectively. Pathway analysis identified nervous system-related methylation changes that are significantly associated with early adenoma development. Integration analysis revealed that DNA methylation in the promoter region of ADHFE1 has the most potential for being an early diagnostic biomarker for colorectal adenoma and cancer (sensitivity = 0.96, specificity = 0.95, area under the curve = 0.97).ConclusionsOverall, we demonstrated that DNA methylation have been shown significant changes in the stage of LGA and HGA in the development of colon cancer. Genome-wide DNA methylation to LGA and HGA provided an important proxy to identify promising early diagnosis biomarkers for colorectal cancer.

The Prospect of Using Serum Taurine Level as a Potential Biomarker for Early Detection of Colorectal Carcinoma and Its Correlation With Other Prognostic Markers

The Prospect of Using Serum Taurine Level as a Potential Biomarker for Early Detection of Colorectal Carcinoma and Its Correlation With Other Prognostic Markers

Histopathological Spectrum of Colorectal Cancer

Background&#x0D; The large bowel is affected by a variety of lesions which include both neoplastic and non-neoplastic lesions. Colorectal cancer is the fourth most common cancer worldwide and one of the leading cause of cancer related deaths.&#x0D; Aims&#x0D; To study the histopathological spectrum of colorectal cancer and evaluate them in relation to the age and sex of the patients and the site of the lesion.&#x0D; Materials and Method&#x0D; Histopathological study of cases of colorectal cancer was carried out in the Department of Pathology, AMCH, Dibrugarh from January 2018 to December 2018.&#x0D; Results&#x0D; Out of a total of 39 cases, 21 were reported in females and 18 in males with the commonest age group involved being 41–60 years. The most common histological type was found to be well differentiated adenocarcinoma and most common site was rectum.&#x0D; Conclusion&#x0D; Early detection of colorectal carcinoma through colonoscopic examination and diagnosis by histopathologic examination is very necessary for proper treatment.

Colonoscopic Review and Surgical Approach in the Management of Colorectal Carcinoma–A Retrospective Study of 50 cases

Introduction: There is no exact statistics about the incidence of colorectal cancer in Bangladesh. According to National Cancer Institute, London, it is the 2nd most common cancer affecting more than 30,000 people in each year. As many patients with colon cancer do not develop symptoms until it is advanced and detection in early stage can only be achieved by screening of asymptomatic person. Maximum patients present lately with distance metastases when there is nothing to treat except palliative therapy. Objectives: To identify the risk factors, early symptoms, signs, treatment modalities, operative outcome, morbidity and mortality rate.&#x0D; Materials and Methods: This retrospective study was carried out at CMH Dhaka during August 2002 to August 2004. A total of 50 patients were taken as study sample. All the patients were admitted in different surgical units of CMH Dhaka for surgical treatment. Detailed history were taken on admission by a questionnaire and examined thoroughly and findings regarding Anaemia, Jaundice, Dehydration, Oedema, Lymphadenopathy, Nutritional status and abnormal signs like ascites, distension, rigidity, organomegaly recorded. Digital rectal examination were done in all cases and finally examined by Proctoscope, Sigmoidoscope and with Colonoscope. FOBT (Fecal Occult Blood Test), serum tumour marker was also assessed.&#x0D; Results: Out of 50 cases 22 were rectal carcinoma and next common site was caecum and number was 10. There was a variation in the sex ratio. Out of 50 cases 33 were male and 17 were female. The highest incidence was among people of 6th decade (28%) and next highest was in 4th decade (24%). Majority of patient with right colon cancer presented with abdominal pain 12 out of 22 cases (56%) and weight loss 15 cases (68%). For left colon cancer commonest symptom was weight loss and weakness and altered bowel habit. Almost all cases with rectal carcinoma presented with bleeding per rectum.&#x0D; Conclusion: About 50% of lesions were found in recto-sigmoid junction and male: female ratio was 1.9:1. All efforts and modern technology should be applied for early detection and treatment. The survival rate is usually very poor in rectal carcinoma. In this study most of the cases were subjected to post operative Chemo and Radiotherapy, but more were treated with neoadjuvant chemoradiation for down staging. The need for early detection of Colorectal Carcinoma (CRC) should be stressed in the form of screening patient awareness and understanding about symptomatology. Early diagnosis and definitive treatment are thereby increasing expectation of higher survival and better prognosis in patient of colorectal carcinoma.&#x0D; Journal of Armed Forces Medical College Bangladesh Vol.11(2) 2015: 36-40

Cancer screening and diagnosis in primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is a progressive liver disease seen predominantly in patients who also have inflammatory bowel disease. PSC is characterised by inflammation and fibrosis of the intra- and extra-hepatic biliary ducts leading to progressive cholestasis, and it frequently leads to decompensated liver disease, necessitating liver transplantation. Patients with PSC and IBD have a predisposition to developing cancer, particularly in the colon and biliary tree. There are no available treatments for PSC; however, the efficacy of simtuzumab and obeticholic acid are being investigated. This article presents evidence and guidelines for screening and early detection of colorectal carcinoma, cholangiocarcinoma and gallbladder cancer, as well as other malignancies, including hepatocellular carcinoma and pancreatic cancer. Nurses have an important role in remaining vigilant for signs of cancer and helping patients make more informed decisions.

Differential expression of mucins in Middle Eastern patients with colorectal cancer.

Mucin overexpression has been implicated in the tumorigenesis and progression of colorectal carcinoma (CRC). However, data obtained on the prognostic importance of mucin expression in CRC is inconsistent. Due to lack of data on mucin expression and the increase in CRC incidence in Saudi Arabia, the aim of the present study was to analyze the mucin expression profile in patients with CRC in this ethnic group. The present study consisted of 22 patients that underwent surgery for CRC. Histopathological and immunohistochemical staining was performed on CRC tumor and adjacent normal tissues. A tissue microarray was prepared from the tumor and normal adjacent samples to investigate the mucin expression profile using immunohistochemistry. Formalin-fixed paraffin-embedded human colorectal cancer tissues were immunostained with mucin 1 (MUC1), mucin 2 (MUC2) and mucin 5AC (MUC5AC) antibodies. Associations between mucin expression and histopathological variables were evaluated. The present study indicated that MUC1 was highly expressed in early (stage I and II; P=0.0016) and late (stage III and IV; P<0.0001) stage CRC tissues compared to normal adjacent tissues. However, MUC2 expression was observed to be downregulated in early and late stage CRC tissues compared to normal and adjacent tissues. Furthermore, serum MUC1 levels were observed to be increased in early and late stage CRC. The present findings indicate that MUC1 expression was significantly higher in early and late stage CRC tissues and MUC2 was downregulated in CRC tissues compared with normal adjacent tissues, and serum MUC1 protein was significantly higher in CRC patients compared to control serum. In conclusion, during colorectal tumorigenesis the pattern of MUC1 and MUC2 expression is altered in Saudi Arabian patients with CRC compared with normal. A higher expression of MUC1 may be used as an independent biomarker in various stages of CRC tumors, which would aid in the early detection of CRC.

Circulating Levels of Adipocytokines as Potential Biomarkers for Early Detection of Colorectal Carcinoma in Egyptian Patients.

Early detection of various kinds of cancers nowadays is needed including colorectal cancer due to the highly significant effects in improving cancer treatment. The aim of this study was to evaluate the potential value of adiponectin, visfatin and resistin as early biomarkers for colorectal cancer patients. Serum levels of adiponectin, visfatin and resistin were measured by a sandwich-enzyme-linked (ELISA) assay technique in 114 serum samples comprising 34 patients with colorectal cancer (CRC), 27 with colonic polyps (CP), 24 with inflammatory bowel disease (IBD) and 29 healthy controls .The diagnostic accuracy of each serum marker was evaluated using receiver-operating characteristic (ROC) curve analysis. The mean concentration of adiponectin was significantly higher in CRC and CP groups than IBD and control groups (P-value <0.05). Also the mean concentration of serum resistin was significantly elevated in the IBD and control groups compared to CRC and CP groups (P-value = 0.014). However, no significant difference was noted in patients of the CRC and CP groups. On the other hand, the mean concentration of visfatin was significantly elevated in CRC and control groups compared to CP and IBD groups (P-value = 0.03). ROC analysis curves for the studied markers revealed that between CRC and IBD groups serum level of adiponectin had a sensitivity of 76.7% and a specificity of 76% at a cut off value of 3940, +LR being 3.2 and -LR 0.31 with AUC 0.852, while serum level of adiponectin between CP and IBD had a sensitivity of 77.8% and a specificity of 75% at a cut off value of 3300, with +LR=3.11 and -LR = 0.3 with AUC 0.852. On the other hand the serum level of visfatin between CRC and CP groups had a sensitivity of 65.5% and a specificity of 66.7 at a cut off value of 2.4, +LR being 1.67 and -LR 0.52 with AUC 0.698. Also the serum level of resistin had a sensitivity of 62.5% and a specificity of 70.3% at a cut off value of 24500, with +LR=2.1 and -LR = 0.53 with AUC 0.685 between control and other groups. On the other hand by comparing control vs CP groups resistin had a sensitivity of 81.8% and a specificity of 70.8% at a cut off value of 17700, with +LR=2.8 and -LR = 0.26 with AUC 0.763 while visfatin had a sensitivity of 68.2% and a specificity of 70.8% at a cut off value of 2.7, with +LR=2.34 and -LR = 0.0.45 with AUC 0.812. These findings support potential roles of adiponectin, visfatin and resistin in early detection of CRC and discrimination of different groups of CRC, CP or IBD patients from normal healthy individuals.

Sensitive and simultaneous determination of 5-methylcytosine and its oxidation products in genomic DNA by chemical derivatization coupled with liquid chromatography-tandem mass spectrometry analysis.

Cytosine methylation (5-methylcytosine, 5-mC) in genomic DNA is an important epigenetic mark that has regulatory roles in diverse biological processes. 5-mC can be oxidized stepwise by the ten-eleven translocation (TET) proteins to form 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-foC), and 5-carboxylcytosine (5-caC), which constitutes the active DNA demethylation pathway in mammals. Owing to the extremely limited contents of endogenous 5-mC oxidation products, no reported method can directly determine all these cytosine modifications simultaneously. In the current study, we developed selective derivatization of cytosine moieties with 2-bromo-1-(4-dimethylamino-phenyl)-ethanone (BDAPE) coupled with liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) for the simultaneous determination of these cytosine modifications in genomic DNA. The chemical derivatization notably improved the liquid chromatography separation and dramatically increased detection sensitivities of these cytosine modifications. The limits of detection (LODs) of the derivatives of 5-mC, 5-hmC, 5-foC, and 5-caC were 0.10, 0.06, 0.11, and 0.23 fmol, respectively. Using this method, we successfully quantified 5-mC, 5-hmC, 5-foC, and 5-caC in genomic DNA from human colorectal carcinoma (CRC) tissues and tumor-adjacent normal tissues. The results demonstrated significant depletion of 5-hmC, 5-foC, and 5-caC in tumor tissues compared to tumor-adjacent normal tissues, and the depletion of 5-hmC, 5-foC, and 5-caC may be a general feature of CRC; these cytosine modifications could serve as potential biomarkers for the early detection and prognosis of CRC. Moreover, the marked depletion of 5-hmC, 5-foC, and 5-caC may also have profound effects on epigenetic regulation in the development and formation of CRC.

Ulcerative colitis: from inflammation to cancer. Do estrogen receptors have a role?

Ulcerative colitis (UC) is a condition at increased risk for colorectal carcinoma (CRC) development. Nowadays, screening and follow-up programs are routinely performed worldwide to promote the early detection of CRCs in subjects with well known risk factors (extent, duration and severity of the disorder). The diffusion of these procedures is presumably the main reason for the marked reduction of cancer incidence and mortality in the course of UC. In addition, chemoprevention has been widely investigated and developed in many medical fields, and aspirin has shown a preventive effect against CRC, while mesalazine has been strongly invoked as a potential chemopreventive agent in UC. However, available studies show some limitations due to the obvious ethical implications of drug withdrawal in UC in order to design a control group. The estrogen receptors (ER) alpha/beta balance seems to have a relevant influence on colorectal carcinogenesis and ER beta appears to parallel apoptosis, and hence an anti-carcinogenic effect. Phytoestrogens are compounds acting as ER beta agonists and have shown a promising chemopreventive effect on sporadic as well as genetically inherited CRC. There is evidence suggesting a role for ERs in UC-related carcinogenesis. In this perspective, since these substances can be considered as dietary supplements and are completely free from side effects, phytoestrogens could be an interesting option for CRC prevention, even when the disease is a consequence of long-term chronic inflammation, as in the course of UC. Further studies of their effects are warranted in both the basic research and clinical fields.

BOWEL CANCER SCREENING–ARE THE PATIENTS TRULY ASYMPTOMATIC?

IntroductionBowel Cancer Screening (BCS) was launched in 2010 in Northern Ireland, with screening colonoscopy lists starting in the Northern Trust in May 2010. Screening is offered every two years to...

Label‐free imaging characteristics of colonic mucinous adenocarcinoma using multiphoton microscopy

Colorectal carcinoma (CRC) has high mortality and increased incidence rates. An early detection of CRC is very important. Multiphoton microscopy (MPM) with high resolution and high sensitivity is used to effectively distinguish the microstructure changes of normal and mucinous adenocarcinoma slices of ex vivo human colonic tissues. In mucinous adenocarcinoma mucosa, the glands are distorted and elongated, the gland cavity is indistinct, and the mesh collagen fibers are diminished. In the submucosa, the collagens are seriously disordered, elongated, pushed aside, and sparsely visible, the content of elastic fibers is also broken and almost disappearing. Many cancer cells, some in cavity-like shape full of mucus surrounded by some collagen fibers, occupied the submucosa, which are comparable to hematoxylin-eosin (HE) stained images. Second harmonic generation and two-photon excitation fluorescence (SHG/TPEF) intensity ratio can be used further to quantitatively evaluate normality and abnormality. The fast Fourier transform (FFT) images show that the normal collagen fibrils are dense and in random order, and the cancerous collagen is certainly organized. The exploratory results show that it has potential for the development of multiphoton mini-endoscopy in real-time early diagnosis of CRC.

Development of Autoantibody Signatures as Biomarkers for Early Detection of Colorectal Carcinoma

To select autoantibody signatures for early detection of colorectal cancer (CRC). A phage cDNA expression library was constructed with fresh tumors from 30 CRC patients and biopanned by using serum pools of 20 CRC patients and 20 healthy controls. A classifier was discovered in the training set of 30 CRC patients at stages I and II and 30 matched healthy controls and then blindly validated in an independent set of 60 CRC patients, 60 healthy controls, 52 polyps patients, and 30 autoimmune diseases patients. Expression of proteins was examined by using immunohistochemistry. Five-phage peptide clones showing higher discriminatory power than others in training set were selected for validation. The five-phage peptide classifier was able to discriminate between early CRC patients and healthy controls, with sensitivities of 90.0% to 92.7% and specificities of 91.7% to 93.3%. In those with serum carcinoembryonic antigen less than 5 ng/mL, the classifier was efficient in discriminating CRC from healthy controls, with an area under the curve of 0.975. The classifier was able to discriminate all of the 9 patients with serrated adenoma from healthy controls. Thirteen (43.3%) of the patients with autoimmune diseases were misclassified. Of the five phage peptides, one encoded a peptide identical to immunoglobulin G (IgG) heavy-chain constant region. IgG immunostaining was stronger in mesenchymal cells than in cancer cells in the tumors and was apparent in serrated adenoma. The five-phage peptide classifier stands out as promising early diagnostic biomarkers for CRC, but it is unsuitable for discriminating CRC from autoimmune diseases. Truncated IgGs generated from the tumors might be novel CRC-associated antigens.

Promoter hypermethylation of RASSF1A, MGMT, and HIC-1 genes in benign and malignant colorectal tumors

Hypermethylation at the promoter region is an important epigenetic mechanism underlying the inactivation of tumor suppressor genes and frequently occurs as an early event in the development of different types of cancer including colorectal carcinoma (CRC). The aim of the present study is the detection of methylation status for some tumor suppressor genes including RASSF1A, MGMT, and HIC-1 in both cancerous and precancerous lesions of colorectal mucosa to evaluate the possibility of developing epigenetic biomarker for early detection of Egyptian CRC. Tissue biopsy was collected from 72 patients (36 CRC, 17 adenomatous polyps, and 19 ulcerative colitis), and in addition, adjacent normal-appearing tissues were collected as control. Promoter hypermethylation status for RSSAF1A, MGMT, and HIC-1 genes was detected after isolation of genomic DNA from the tissues samples using methylation-specific PCR technique. High frequency of methylation at MGMT, RASSFA, and HIC-1 was detected in CRC patients (25%, 47.2%, and 41.7% respectively). The highest methylation detected in adenomatous polyps patients was in MGMT gene (47.1%) followed by 35.3% for HIC-1 and only 5.9% for RASSF1A gene. HIC-1 gene exhibited highest frequency of methylation in ulcerative colitis patients (57.8%) whereas it was 26.3% for both RASSF1A and MGMT genes. A nonsignificant association was recorded between the methylation status in different genes examined with the clinicopathological factors except the association between methylation at RASSF1A gene with gender (p=0.005), and it was significant. In conclusion, aberrant hypermethylation at promoter region of RASSFA, MGMT, and HIC-1 genes is involved in Egyptian CRCs. Hypermethylation of MGMT and HIC-1 genes plays an important role in the initiation of disease especially ulcerative colitis-carcinoma pathway.

Colonoscopy Screening in Germany

Early detection of colorectal carcinoma is a genuine precaution against colorectal cancer, because tumor precursors can be identified and removed. This means that invasive carcinoma can be prevented and incidence in the population can be reduced in the long term. However, when a new screening measure such as colonoscopy is introduced, there is a short-term increase in incidence, as more tumors are identified. Since 1977, the fecal occult blood test has been one of the bowel cancer screening procedures available according to statutory health insurance in Germany. In 2002, preventive colonoscopy was added as an alternative to the fecal occult blood test; in other words, those with statutory health insurance can choose which screening method is used (source: www.zi-berlin.de; consulted on October 2, 2010). Fecal occult blood tests can be performed annually between the ages of 50 and 55, and then every two years. A possible alternative to this is preventive colonoscopy from the age of 55, repeated 10 years later. If the results of a fecal occult blood test are unusual or a patient suffers any pains, a curative colonoscopy is still performed for clarification.