Development Of Colorectal Adenocarcinoma Research Articles

Malignant polyps in the COVID-19 era: a population-based analysis.

Malignant polyps represent the early development of colorectal adenocarcinoma. During 2020, there was widescale rationing of health-care resources in response to the COVID-19 pandemic. In particular there was deferral of some colonoscopy procedures required for timely malignant polyp detection. This study sought to assess how these deferrals affected the diagnosis of malignant polyps. A population wide analysis was performed of 2079 malignant polyps, diagnosed in Queensland, Australia from 2011 to 2020. A regression analysis, with 95% prediction intervals, was produced to determine whether there was a significant impact on the number of malignant polyps diagnosed in 2020 compared to previous years. Univariate statistical analysis of patient, procedural, and pathological variables was also performed. In 2020 there were 211 malignant polyps diagnosed, which was significantly lower than was predicted by the univariate regression analysis (r2 = 0.85, 95% prediction interval: 255.07-323.91, P< 0.001). These malignant polyps were less likely to be diagnosed in a private setting (P< 0.001), and exhibited significantly less depth of submucosal invasion (P= 0.017). There was no significant difference in the management strategy (polypectomy, resection or trans-anal resection) between 2011 and 2019 and 2020. Because of the significant decrease in the number of malignant polyps, and the natural history of the disease, it is expected that there will be an increase in more advanced colorectal adenocarcinomas presenting in 2021 and beyond. This has implications for healthcare resources, particularly in light of the ongoing strain on health departments as a result of the COVID-19 pandemic.

LncRNA LINC02535 Induces Colorectal Adenocarcinoma Progression via Modulating miR-30d-5p/CHD1.

Growing evidence has suggested that lncRNAs play a significant role in the development of colorectal adenocarcinoma. LncRNA LINC02535 was a potential novel lncRNA marker of neoplastic processes of the colon. Nevertheless, the function and mechanisms of LINC02535 in colorectal adenocarcinoma remain unclear. Proteins levels were measured by western blotting. EdU, CCK-8, Transwell, and wound healing assays were performed to investigate the function of LINC02535 in colorectal adenocarcinoma. The distribution of LINC02535 in cells was evaluated by subcellular fractionation assay. The interaction among RNAs was identified by luciferase reporter and RIP assays. In this study, our findings revealed that LINC02535 was highly expressed in colorectal adenocarcinoma cells. Knockdown of LINC02535 inhibited colorectal adenocarcinoma cell proliferation, migration, and invasion. Mechanistically, LINC02535 bound with miR-30d-5p and worked as a competing endogenous RNA to facilitate the expression of messenger RNA chromodomain helicase DNA-binding protein 1 (CHD1). miR-30d-5p directly targeted the sequence of CHD1 3'-untranslated region. Notably, CHD1 upregulation abolished the suppressive influence of LINC02535 inhibition on the malignant phenotypes of colorectal adenocarcinoma cells. Overall, it was disclosed that LINC02535 played an oncogenic role in colorectal adenocarcinoma progression by sponging miR-30d-5p to upregulate CHD1 expression.

Identification of Hub Genes in Colorectal Adenocarcinoma by Integrated Bioinformatics.

An improved understanding of the molecular mechanism of colorectal adenocarcinoma is necessary to predict the prognosis and develop new target gene therapy strategies. This study aims to identify hub genes associated with colorectal adenocarcinoma and further analyze their prognostic significance. In this study, The Cancer Genome Atlas (TCGA) COAD-READ database and the gene expression profiles of GSE25070 from the Gene Expression Omnibus were collected to explore the differentially expressed genes between colorectal adenocarcinoma and normal tissues. The weighted gene co-expression network analysis (WGCNA) and differential expression analysis identified 82 differentially co-expressed genes in the collected datasets. Enrichment analysis was applied to explore the regulated signaling pathway in colorectal adenocarcinoma. In addition, 10 hub genes were identified in the protein–protein interaction (PPI) network by using the cytoHubba plug-in of Cytoscape, where five genes were further proven to be significantly related to the survival rate. Compared with normal tissues, the expressions of the five genes were both downregulated in the GSE110224 dataset. Subsequently, the expression of the five hub genes was confirmed by the Human Protein Atlas database. Finally, we used Cox regression analysis to identify genes associated with prognosis, and a 3-gene signature (CLCA1–CLCA4–GUCA2A) was constructed to predict the prognosis of patients with colorectal cancer. In conclusion, our study revealed that the five hub genes and CLCA1–CLCA4–GUCA2A signature are highly correlated with the development of colorectal adenocarcinoma and can serve as promising prognosis factors to predict the overall survival rate of patients.

Wnt7a Promotes the Occurrence and Development of Colorectal Adenocarcinoma.

ObjectiveThe expression of Wnt7a in colorectal cancer tissues and cell lines was analyzed, and the effect of Wnt7a on the proliferation of colorectal cancer cells was studied, so as to confirm the relationship between Wnt7a and the occurrence and development of colorectal cancer.Methods(1) Immunohistochemical method was used to compare the expression of Wnt7a in different tissues and its relationship with the clinicopathology of colorectal adenocarcinoma. (2) The expression levels of Wnt7a in colorectal cancer cell lines HT-29 and HCT 116 were detected by qRT-PCR. (3) The down-regulated Wnt7A expression vector was constructed, and the down-regulated Wnt7A expression cell line was established. The regeneration ability of cancer cells was detected by stem cell ball formation assay, and the influence of plate cloning assay on the proliferation ability of colorectal cancer cells was detected.Results(1) The positive rates of Wnt7a in normal colorectal mucosa, colorectal adenoma and colorectal adenocarcinoma tissues gradually increased,Wnt7a are closely related to the degree of colorectal adenocarcinoma differentiation, lymph node metastasis and Duke stage. (2) The expression level of Wnt7a in colorectal cancer cells was higher than that in normal colorectal epithelial cells. (3) The down-regulation of Wnt7A reduced the proliferation ability of colorectal cancer cells.ConclusionsWnt7a promotes the occurrence and development of colorectal adenocarcinoma.

COLORECTAL ADENOCARCINOMA DEVELOPING IN A YOUNG FEMALE WITH OVERLAP SYNDROME AND VERY EARLY ONSET-INFLAMMATORY BOWEL DISEASE: A CASE REPORT

Abstract We present a 4-year-old female diagnosed with very-early onset inflammatory bowel disease (VEO-IBD), ulcerative colitis type, and overlap syndrome based on clinical presentation, blood and stool studies, diagnostic endoscopies and liver biopsy. Her clinical course was complicated by pervasive psychological stressors, non-compliance with medical therapy, and frequent provider changes. Initial treatment included Prednisone, 6-mercaptopurine and Ursodiol. Treatment was escalated to include multiple biological agents which were stopped prematurely due to non-adherence. She developed weight loss and growth stunting, necessitating exclusive enteral nutrition and then parenteral nutrition. Due to medically refractory disease, she underwent a total colectomy with end ileostomy at the age of 13. Pathology revealed stage III colorectal adenocarcinoma (CRC) with lymph node involvement and transmural inflammation diagnostic of Crohn’s disease (CD). Genetic testing of the resected colon noted a missense mutation of TP53. Our patient completed 6 cycles of extensive and targeted chemotherapy with no evidence of disease reccurrence. She recently underwent ileal pouch-anal anastomosis and creation of a diverting ileostomy. CRC is exceedingly rare in pediatric IBD (PIBD) patients, with less than 30 reported cases in the available literature1. Most cases occurred in males and patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC), where the risk of developing CRC is four times greater2. The risk of CRC increases with disease duration, with most PIBD patients developing CRC at 25 years of age1. Interestingly, mutations in TP53, a tumour suppressor gene, have been found to occur more frequently in patients with IBD-CRC compared to those with sporadic-CRC or IBD without dysplasia3. Mutations in TP53 may not only increase a patients general susceptibility to CRC but may also accelerate its development by contributing to excessive inflammation4. Our patient’s treatment refractory clinical course and transition in IBD diagnosis from UC to CD highlights the complexity of VEO-IBD management. While rare in pediatric patients, the development of CRC is a life-threatening risk and it should be considered in patients with prolonged and severely refractory IBD with concomitant autoimmune liver disease. Our patient’s young age at the time of CRC diagnosis emphasizes the need for vigilant yearly endoscopic screening and development of pediatric guidelines for dysplasia monitoring in this high risk population. Further research is needed to evaluate the role of genetic variant screening in CRC risk stratification.

Immunohistochemical study of CD44 in сolorectal adenocarcinoma

Background. Over the last decade, a significant amount of data supporting the cancer stem cell hypothesis has been accumulated. Despite the large number of works devoted to the study of the stem cell marker CD44 in colorectal adenocarcinoma, the question of the prognostic value of this marker is still controversial. Objective. To study CD44 immunohistochemical expression in colorectal adenocarcinoma on the I, II, III, IV stages (pTNM). Methods. Pathohistological and immunohistochemical studies of surgical material from 30 patients that underwent surgical treatment of colorectal adenocarcinoma (I–IV stages) were carried out. Polyclonal antibodies CD44 (CD44 Std. / HCAM Ab-4, Thermo Scientifiс, USA) were used for immunohistochemical study. Results. 16,7% of all the studied cases were stage I colorectal adenocarcinomas, 26,7% – stage II colorectal adenocarcinomas, 33,3% – stage III colorectal adenocarcinomas, and 23,3% – stage IV colorectal adenocarcinomas. It was established that colorectal adenocarcinoma is characterized by the medium membrano-cytoplasmic expression of CD44 with the median 90,49 (62,19; 110,15) CUOD that statistically significantly higher than CD44 expression level in non-changed mucosa of the distal colon. There is a tendency to increasing of expression level of the marker in sequence of the stages of colorectal adenocarcinoma development, wherein median of CD44 expression in stage II carcinomas is significantly higher than the same characteristic in stage I carcinomas (70,32 (55,13; 90,56) CUOD vs. 51,12 (31,14; 60,32) CUOD, р˂0,05), and median of CD44 expression in stage III carcinomas is significantly higher than the same characteristic in stage II carcinomas (104,76 (90,03; 112,26) CUOD vs. 70,32 (55,13; 90,56) CUOD, р˂0,05). Furthermore, correlations between CD44 expression level and depth of tumor’s invasion (r=0,48, p˂0,05), presence of regional metastases (r=0,53, p˂0,05), presence of distant metastases (r=0,38, p˂0,05), histological grade of the tumor (r=0,27, p˂0,05) were revealed. Conclusion. CD44 immunohistochemical expression increases significantly during the progression of colorectal adenocarcinoma from stage I to stage III (pTNM), as well it correlates with depth of the tumor’s invasion, presence of regional and distant metastases, and with histological grade of the tumor.

LncRNA-AWPPH activates TGF-β1 in colorectal adenocarcinoma.

Long non-coding RNA associated with poor prognosis of hepatocellular carcinoma (lncRNA-AWPPH) is a newly discovered lncRNA that has important functions in the pathogenesis of several malignancies. However, its role in the development of colorectal adenocarcinoma is unknown. The current study therefore investigated the function of AWPPH in colorectal adenocarcinoma. A total of 86 patients with colorectal adenocarcinoma and 56 healthy controls were included. Tumor tissues and adjacent healthy tissues were collected from patients with colorectal adenocarcinoma, and blood was collected from both patients and healthy controls. Expression of AWPPH in tissues and blood was detected by the reverse transcription-quantitative polymerase chain reaction. Receiver operating characteristic curve analysis was used to evaluate the diagnostic value of serum AWPPH for colorectal adenocarcinoma. All patients were followed up for 5 years, and survival curve analysis was performed to investigate the association between serum level of AWPPH and patients' survival. The effects of AWPPH overexpression and silencing in colorectal adenocarcinoma cell lines were investigated. Effects on cell proliferation and viability were detected by the cell counting kit-8 and MTT assays, respectively. Effects on transforming growth factor β1 (TGF-β1) expression were determined by western blotting. AWPPH was significantly upregulated in tumor tissues compared with adjacent healthy tissues. AWPPH expression levels in blood increased in patients with colorectal adenocarcinoma compared with healthy controls, suggesting that AWPPH may be a sensitive and accurate diagnostic and prognostic biomarker for colorectal adenocarcinoma. AWPPH overexpression in colorectal adenocarcinoma cell lines promoted cell proliferation and increased cell viability, while AWPPH silencing resulted in opposite effects. AWPPH overexpression promoted and silencing inhibited TGF-β1 expression. Therefore, lncRNA-AWPPH promoted colorectal adenocarcinoma by promoting tumor growth, increasing tumor cell viability and activating the TGF-β1 signaling.

The features of KRAS gene transcriptional activity and significance in colorectal cancer

Colorectal adenocarcinoma (CRA) is the result of numerous mutations accumulation. The aim of the work was to study KRAS gene transcriptional activity at I, II, III, and IV stages of CRA development and to analyze the correlations between KRAS and Ki-67, TP53, CDH1, CTNNB1 genes transcriptional activity. Pathohistological and molecular-genetic study of surgical material from 40 patients with CRA, as well as sectional material of 10 fragments of the distal colonic wall was conducted. The following statistical methods were used: descriptive statistics, χ2 test, Kruskal-Wallis test, Spearman’s rank correlation coefficient. It was established that CRA is characterized by increased KRAS transcriptional activity: Me of mRNA expression is 0.42 (0.36; 0.43) at stage I, 1.31 (1.09; 2.91) at stage II, 1.75 (1.31; 2.93) at stage III, and 2.91 (1.85; 3.50) at stage IV. Decreasing of Ki-67 gene transcriptional activity was revealed: Me of mRNA expression is 3.20 (2.31; 3.59) at stage I, 2.92 (1.80; 3.50) at stage II, 1,27 (1.19; 2.08) at stage III, and 0.52 (0.28; 1.04) at stage IV. As about TP53 gene, increasing of transcriptional activity was detected: Me is 2.15 (0.82; 2.30) at stage I, 2.80 (1.32; 4.50) at stage II, 3.80 (2.32; 6.50) at stage III, 7.80 (5.99; 8.92) at stage IV. Also, a direct medium correlation between the KRAS and TP53 transcriptional activity levels was revealed. There is a decreasing of CDH1 transcriptional activity: Me is 0.88 (0.42; 1.14) at stage I, 0.48 (0.23; 1.13) at stage II, 0.15 (0.09; 0.36) at stage III and 0.08 (0.04; 0.41) at stage IV. A reverse medium correlation between KRAS and CDH1 was revealed. The study of CTNNB1 gene mRNA at different stages of CRA indicated the absence of statistically significant difference: Me is 2.88 (2.38; 5.38) at stage I, 3.83 (2.59; 5.99) at stage II, 2.02 (1.38; 6.95) at stage III, and 2.27 (1.23; 2.93) at stage IV. So, KRAS gene transcriptional activity increases from I to IV stages in CRA, affecting apoptosis and adhesive properties of cancer cells.

Features of CDH1, CTNNB1 genes transcriptional activity and expression levels of E-cadherin, β-catenin proteins coded by these genes on the I, II, III, IV stages of colorectal adenocarcinoma development

Aim – analysis of CDH1 and CTNNB1 genes mRNA expression levels and expression levels of E-cadherin, β-catenin proteins coded by these genes, and also their correlations with KRAS gene transcriptional activity level on the I, II, III, IV stages (pTNM) of colorectal adenocarcinoma (CRA) development. Materials and methods. Parallel immunohistochemical and molecular-genetic, pathohistological studies of operational material of CRA from 40 patients (4 study groups – I, II, III, IV stages according to pTNM classification – 10 cases in each group) with diagnosis of colorectal adenocarcinoma, and sectional material of 10 fragments of distal colonic wall with normal histological structure were conducted. Results. In comparison with unchanged mucosa of distal colon CRA is characterized by the decreased CDH1 gene transcriptional activity. There is the tendency to reducing of CDH1 gene mRNA expression in the study groups – from the I to the IV stages of the tumor development. CRA is characterized by the low E-cadherin expression level, which also has the tendency to reducing in the study groups. Moreover, in comparison with unchanged mucosa of distal colon CRA is characterized by the increased CTNNB1 gene transcriptional activity and the high β-catenin expression level. There aren’t statistically significant differences between the CTNNB1 gene mRNA, β-catenin expression levels in the study groups. There are direct correlations between the expression levels of the studied genes and the molecules, coded by these genes, and also reverse correlations between the KRAS and CDH1 genes mRNA expression levels, the KRAS gene mRNA expression level and the E-cadherin expression level, direct correlation between the KRAS gene mRNA expression level and the β-catenin expression level. Conclusions. CRA is characterized by the decreased CDH1 gene transcriptional activity that correlates with the low E-cadherin expression level, and by the increased CTNNB1 gene transcriptional activity that correlates with the high β-catenin expression level. The CDH1 gene transcriptional activity and the expression level of E-cadherin, which is coded by this gene, decrease during the CRA progression from the I to the IV stages. CRA is characterized by reverse correlations between the KRAS and CDH1 genes mRNA expression levels, the KRAS gene mRNA expression level and the E-cadherin expression level, direct correlation between the KRAS gene mRNA expression level and the β-catenin expression level.

Downregulation of transcription factor EB inhibits the growth and metastasis of colorectal carcinomas

To determine the roles of transcription factor EB (TFEB) in colorectal cancer (CRC), we collected samples of tumor tissues and normal tissues from 40 patients with CRC. The expression of TFEB in these samples was analyzed by using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Furthermore, we explored the expression of TFEB mRNA in CCD-18Co normal cells and HT-29, HCT-8, C2BBe1 cancer cells. HT-29, HCT-8, and C2BBe1 cancer cells were transfected with a TFEB-specific small interference RNA (siRNA) and scrambled siRNA, then the TFEB expression was confirmed by Western blot. The migration and invasion abilities of cells transfected with TFEB-siRNA were examined by transwell method and wound-healing assay. The subsequent effect of TFEB silencing on the tumor growth was also detected in mice xenograft model in vivo. Our study found that TFEB expression was significantly increased ( P &lt; 0.05) in colorectal tumor tissues compared with normal tissues. Consistent with TFEB expression in tissues, compared with the normal CCD-18Co cells, TFEB mRNA expression was also significantly augmented in CRC cells. TFEB protein expression was markedly reduced in HT-29, HCT-8, and C2BBe1 cells after TFEB-siRNA transfection. In addition, inhibition of TFEB expression resulted in decrease of cells migration and invasion abilities. In vivo study, compared with the negative control group, the tumor weight, and volume were also reduced after inhibiting the TFEB expression. Our research suggested that TFEB expression is related to the occurrence and development of colorectal adenocarcinoma. The migration and invasion abilities of cancer cells, the weight and volume of tumor were all decreased when inhibiting TFEB expression. Thus, TFEB serves as an important factor in the development of CRC by modulating cancer cell migration and invasion, showing the potential therapeutic target of CRC in clinical.

Parkin protein expression and its impact on survival of patients with advanced colorectal cancer.

Objective:Features of colorectal cancer such as natural history, molecular, chromosomal, and epigenetic alterations have been well described. However, there is still a lack of accurate prognostic markers, which is evident by the lower overall survival rates of patients with advanced cancer. Although alterations in parkin protein expression have been described in colorectal cancer, the functional significance of this protein remains unknown. The present study aimed to investigate the involvement of parkin expression in colorectal adenocarcinoma development and progression by evaluating the association between its expression, clinicopathological parameters, and expression of known proteins involved in colorectal cancer.Methods:Tissue microarrays consisting of 73 tumor and 64 normal tissue samples were generated to examine parkin expression and localization by immunohistochemistry.Results:A positive correlation of parkin and APC expression was observed in the superficial, intermediate, and profound regions of all cases (ρ = 0.37; P = 0.001). Parkin expression was also significantly associated with tumors in men (P = 0.049), those of the mucinous subtype (P = 0.028), and of advanced stage (III + IV, P = 0.041). In addition, increased parkin expression was observed in the invasive front tumor region (P = 0.013). More importantly, a positive correlation was found between parkin expression and the overall survival of patients with advanced colorectal cancer (P = 0.019). Multivariate analysis showed that parkin expression was independent of any of the clinicopathological parameters evaluated in relation to patient survival. Conclusions:These results suggest that parkin expression status can be used as a potential independent prognostic marker of survival in advanced colorectal cancer.

Aggressive large-cell neuroendocrine carcinoma of the sigmoid colon in a patient with ulcerative colitis

Colonic inflammation seen in inflammatory bowel disease (IBD) predisposes to the development of colorectal adenocarcinoma. In contrast, colorectal neuroendocrine carcinomas (NECs) have rarely been reported in the setting of IBD,...

BK polyomavirus association with colorectal cancer development.

The development of human neoplasms can be provoked by exposure to one of several viruses. Burkitt lymphoma, cervical carcinoma, and hepatocellular carcinoma are associated with Epstein-Barr, human papilloma, and hepatitis B virus infections, respectively. Over the past three decades, many studies have attempted to establish an association between colorectal cancer and viruses, with debatable results. The aim of the present research was to assess the presence of BK polyomavirus (BKV) DNA and protein in colorectal cancer samples from patients in the Western Province of Saudi Arabia. DNA extracted from archival samples of colorectal cancer tissues was analyzed for BKV sequences using polymerase chain reaction (PCR)-based techniques. In addition, expression of a BKV protein was assessed using immunohistochemical staining. None of the tumor and control samples examined tested positive for BKV DNA in PCR assays. Furthermore, immunohistochemical staining failed to detect viral proteins in both cancer and control specimens. These results may indicate that BKV is not associated with the development of colorectal adenocarcinoma in patients in the Western Province of Saudi Arabia.

Correlation of caveolin-1 expression with microlymphatic vessel density in colorectal adenocarcinoma tissues and its correlation with prognosis.

To study the expression of caveolin-1 in colorectal adenocarcinoma tissues and its correlation with microlymphatic vessel density (LMVD), and to investigate the clinical pathological prognostic significance of caveolin-1 and LMVD in patients with colorectal cancer. The expression of caveolin-1 and LMVD in 45 specimens of normal colorectal tissues, and 90 specimens of colorectal adenocarcinoma tissues were detected by immunohistochemistry technique. The correlation between their expression and the clinicopathologic features was analyzed. Multivariable Cox regression was used to analyze the association between the laboratory indices and overall survival time. The positive rates of caveolin-1 in colorectal adenocarcinoma tissues were significantly higher than those in normal colorectal tissues (P<0.01). LMVD in colorectal adenocarcinoma tissues were significantly higher than those in normal colorectal tissues (P<0.01). Mean LMVD in group with caveolin-1 positive was significantly higher than in that with caveolin-1 negative. The median survival time was 26.7 months. Cox regression analysis showed that the caveolin-1 expression, invation depth, lymph node metastasis, TNM stage, liver metastasis and LMVD were independent risk factors of overall survival time of patients with colorectal carcinoma. Caveolin-1 may contribute to the lymphangiogenesis in the tumor. During the occurrence and development of colorectal adenocarcinoma, there is a close relationship between the expression of caveolin-1 and lymphatic microvessel of tumor. Caveolin-1 expression and microlymphatic vessel density are significant prognostic value of colorectal carcinoma.

Quantitation of microRNA-92a in colorectal adenocarcinoma and its precancerous lesions: Co-utilization of in situ hybridization and spectral imaging.

The expression level of microRNA (miR)-92a has been proven to increase during the development of colorectal adenocarcinoma (CA) and has been verified at the cellular, plasma and fecal levels by various quantitative methods. However, a method to quantitate the expression level using tissue sections has not been established. To do this, in situ hybridization (ISH) and multispectral imaging microscopy (MSI) were introduced to quantitate miR-92a expression on the microscopic level. ISH of miR-92a was first performed on 34 tissue samples of CA and adenomas with high-grade and low-grade intraepithelial neoplasms, while 31 paralesional normal tissue samples were defined as the control. Subsequently, a MSI technique was applied to quantitate the hybridization signal in terms of optical density (OD) at the visible wavelength. A t-test with unequal variance was used to examine the statistical significance between the groups. Despite all 34 tissue sections demonstrating at least partial positivity of miR-92a expression following ISH, visual grading was inconclusive. As such, the signal of ISH was transformed in terms of OD and further analyzed by employing the MSI system. A statistically significant difference was observed between the expression levels of miR-92a in CA and the paralesional normal controls. By contrast, a poor correlation was revealed between visual and spectral grading. The co-utilization of ISH and MSI generated a legible observation in the expression level of miR-92a, revealing the dynamic change in miR-92a expression in the progression of the disease and providing important information for further functional investigation.

C936T polymorphism of the VEGF gene in relation to the risk and the clinical and biological characteristics of sporadic colorectal adenocarcinoma.

BackgroundOne of the main glycoproteins responsible for angiogenesis is the vascular endothelial growth factor. It is believed that C936T polymorphism, located in the VEGF gene, is correlated with susceptibility towards development of sporadic colorectal adenocarcinoma. The aim of this study was to identify the frequencies of the genotypes of C936T polymorphism of the VEGF gene in patients with sporadic colorectal adenocarcinoma, in comparison with controls, and whether this correlates with the degree of tumor invasion, lymph node involvement and occurrence of metastases at the time of the diagnosis. The analysis was done on 261 patients with sporadic colorectal adenocarcinoma and 261 controls. The genotypes of C936T polymorphism were evaluated by means of the polymerase chain reaction and enzyme digestion, using peripheral blood samples.ResultsThe occurrences of genotype 936CC were similar in the two groups (80.5% versus 78.5%, p = 0.2288). In relation to tumor location, lymph node involvement, infiltration and tumor metastasis, no statistically significant results were obtained (p = 0.3116, p = 0.8485, p = 0.9408 and p = 0.2861, respectively).ConclusionC936T polymorphism of the VEGF gene did not influence the occurrence of sporadic colorectal adenocarcinoma development and did not correlated with the degree of tumor invasion, lymph node involvement and occurrence of metastases.

Immunohistochemical evaluation of BCL-2 and KI-67 proteins in colorectal adenoma.

&#x0D; &#x0D; &#x0D; &#x0D; J Fac Med Baghdad&#x0D; 2014; Vol.56, No .2&#x0D; Received Jan .2014&#x0D; Accepted Mar. 2014&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; Background: Development of colorectal adenocarcinoma principally occurs via the adenoma- carcinoma sequence of a multiple step process of tumor progression. This results from an accumulation of genetic changes in cells of intestinal mucosa. The use of molecular biomarkers may further aid in determining the risk of changing to carcinoma.&#x0D; Objectives: To evaluate the expression of Bcl-2 and Ki-67 in colorectal adenomas and correlate the observed levels with age, gender, histological type, grades of dysplasia as well as to the levels of these two markers with each other.&#x0D; Materials and Methods: A retrospective stu dy of fifty colorectal biopsies were selected randomly, 40 cases were with different grades of colorectal adenomas and 10 cases with normal mucosa as a control group; covering the period from 2010 till 2012. All the cases collected from the Gastroenterology and Hepatology Teaching Hospital. The biopsies were re-examined histologically and then stained immunohistochemically for Ki-67 and Bcl-2.&#x0D; Results: There was a significant correlation only between Ki-67 expression and grade of adenoma and there was a significant correlation between Ki-67 and Bcl-2 expression in adenoma. Also there was a significant correlation between age of the patients and histologic type.&#x0D; Conclusions: The assay of Ki-67 and Bcl-2 is valuable in detecting the risk of early colorectal carcinogenesis in patients with colorectal adenomas. Ki-67 expression increases with progression of the grade of adenoma while BCL-2 decrease with progression of the grade.

Label-free monitoring of colorectal adenoma–carcinoma sequence based on multiphoton microscopy

The monitoring and evaluation of colorectal adenoma–carcinoma sequence during endoscopy are important for endoscopic resection of precursor lesions to disrupt the adenoma–carcinoma sequence and halt progression to invasive neoplastic disease. In this study, multiphoton microscopy (MPM) was used to identify different stages during the development of colorectal adenocarcinoma including adenoma with low-grade and high-grade dysplasia, and adenocarcinoma invading the submucosa. It was found that by combining two-photon excited fluorescence (TPEF) imaging and second harmonic generation (SHG) imaging, MPM can reveal the morphological changes of the epithelial cells and glands, identify the invasive position and depth of atypical glands and quantitatively describe the change of the cellular nucleus and the nuclear-to-cytoplasmic ratio during the stepwise progression of colorectal adenocarcinoma. These are important pathological findings for pathologists when diagnosing colorectal lesions. With the advancement of a compact and flexible multiphoton endoscope for in vivo imaging and clinical applications, MPM has the potential to provide immediate histological diagnosis for the monitoring and evaluation of the colorectal adenoma–carcinoma sequence during endoscopy.

Expression of MACC1 and MET in Inflammatory Bowel Disease-associated Colonic Neoplasia

Metastasis-associated in colon cancer-1 (MACC1), a newly identified regulator of HGF-MET signaling, may participate into the key steps of sporadic colorectal adenocarcinoma development. Given there are many pathogenetic distinctions between colitis-associated colorectal cancer (CAC) and sporadic colorectal adenocarcinomas, the potential roles of MACC1 in CAC carcinogenesis remain unknown. For the first time, we evaluated the expressions of MACC1 and MET in IBD-associated colitis, dysplasia, and adenocarcinoma. Expression was investigated by immunohistochemistry in tissue microarrays consisting of 13 normal colon, 11 active colitis, 9 dysplasia, 51 conventional CAC, 5 mucinous adenocarcinoma, and 1 signet ring cell adenocarcinoma specimens. The expression level of MACC1 or MET was evaluated with H-score system. MACC1 expression was significantly higher in IBD-associated dysplasia than that in corresponding inflammatory or normal colonic tissue, and its level was further elevated from dysplasia to conventional CAC. Higher MACC1 expression was seen in a patient with CAC who had multifocal dysplasia or synchronous carcinoma. MACC1 overexpression (H-score >100) was seen in 67% of conventional CAC but in 0% of dysplasia and 0% of inflammation or normal colon. There was no difference of MACC1 expression found among well, moderately and poorly differentiated CAC. MET expressions in inflammation, dysplasia, and conventional CAC were statistically similar. No parallel expression of MACC1 and MET was detected in this study. MACC1 and MET expression was not increased in mucinous or signet ring cell carcinoma, 2 distinct variants of CAC. Stepwise increase of MACC1 expression from IBD-associated colitis to dysplasia to adenocarcinoma suggests that MACC1 is strongly associated with conventional CAC tumorigenesis in a manner independent of MET. MACC1 may serve as a potential marker for early diagnosis of conventional CAC.

MUC15 Inhibits Dimerization of EGFR and PI3K–AKT Signaling and Is Associated With Aggressive Hepatocellular Carcinomas in Patients

Aberrant expression of MUC15 correlates with development of colorectal adenocarcinoma, and MUC15 has been reported to prevent trophoblast invasion of human placenta. However, little is known about the role of MUC15 in pathogenesis of hepatocellular carcinoma (HCC). We analyzed HCC samples and matched nontumor liver tissues (controls) collected from 313 patients who underwent hepatectomy in Shanghai, China, from January 2006 through September 2009. Levels of messenger RNAs and proteins were determined by immunohistochemical, quantitative reverse transcription polymerase chain reaction, and immunoblot analyses. Statistical analyses were used to associate levels of MUC15 with tumor features and patient outcomes. Levels of MUC15 messenger RNA and protein were reduced in a greater percentage of HCC samples than control tissues. Tumors with reduced levels of MUC15 were more likely to have aggressive characteristics (eg, high levels of α-fetoprotein, vascular invasion, lack of encapsulation, and poor differentiation) than those with low levels. Patients whose tumors had reduced levels of MUC15 had shorter overall survival times (24 months vs 46 months for patients with tumors with high levels of MUC15) and time to disease recurrence. Stable expression of MUC15 in HCC cell lines (SMMC-7721 and HCC-LM3) reduced their proliferation and invasive features in vitro, and ability to form metastatic tumors in mice. MUC15 reduced transcription of the matrix metalloproteinases 2 and 7 increased expression of tissue inhibitor of metalloproteinase-2, which required phosphoinositide 3-kinase-v-akt murine thymoma viral oncogene homolog signaling. Physical interaction between MUC15 and epidermal growth factor receptor led to its relocation and degradation within early endosomes and was required for inactivation of phosphoinositide 3-kinase-v-akt murine thymoma viral oncogene homolog signaling. Reduced levels of MUC15 in HCCs are associated with shorter survival times of patients and reduced time to disease recurrence. Expression of MUC15 in HCC cells reduces their aggressive behavior in vitro and in mice by inducing dimerization of epidermal growth factor receptor and decreasing phosphoinositide 3-kinase signaling via v-akt murine thymoma viral oncogene homolog.