Expression In Colorectal Adenocarcinoma Research Articles

The Relation between Histopathological Features and P53 Expression in Colorectal Adenocarcinoma in Ugandan Patients

The Relation between Histopathological Features and P53 Expression in Colorectal Adenocarcinoma in Ugandan Patients

Quantitative parameters of dual-layer spectral detector computed tomography for evaluating Ki-67 and human epidermal growth factor receptor 2 expression in colorectal adenocarcinoma.

Ki-67 and human epidermal growth factor receptor 2 (HER2) are key biomarkers in evaluating the prognosis of colorectal adenocarcinoma (CRAC). The purpose of this study was to investigate the value of quantitative parameters in dual-layer spectral detector computed tomography (SDCT) for evaluating the expression of Ki-67 and HER2 in CRAC. In this retrospective, cross-sectional study, 88 eligible patients with pathologically confirmed CRAC were selected from Taicang Hospital of Traditional Chinese Medicine between May 2021 and April 2023. The study participants underwent enhanced SDCT of the whole abdomen within 2 weeks before to surgery, did not receive antitumor therapy, and had complete immunohistochemical (IHC) indexes. Patients with nonadenocarcinoma pathologic types, poor quality of spectral CT images, or no complete immunohistochemistry results were excluded. Spectral parameters including CT values at 40 and 100 keV, effective atomic number, iodine concentration (IC), the slope of the spectral Hounsfield unit (HU) curve (λHU), and normalized iodine concentration (NIC) in the arterial phase (AP) and venous phase (VP) were analyzed for their value in distinguishing between the high and low expression of Ki-67 and HER2-positive and -negative status in CRAC. The statistical significance of the SDCT parameters between the different groups of Ki-67 expression and those of HER2 status was assessed with the Mann-Whitney test. Spearman correlation analysis was used to analyze the correlation between the SDCT parameters and the extent of Ki-67 expression and HER2 expression status. The receiver operating characteristic (ROC) curve was used, and the area under the curve (AUC) was calculated. The SDCT parameters of CT values at 40 keV, effective atomic number, IC, and the λHU in the VP showed significant differences between the Ki-67 high- and low-expression groups in CRAC (P=0.035, P=0.041, P=0.036, and P=0.044, respectively), with AUCs of 0.639 [95% confidence interval (CI): 0.512-0.766], 0.634 (95% CI: 0.508-0.761), 0.638 (95% CI: 0.510-0.766), and 0.633 (95% CI: 0.504-0.762), respectively. The expression of CRAC Ki-67 was positively correlated with CT values at 40 keV (r=0.227; P=0.034), effective atomic number (r=0.219; P=0.040), IC (r=0.225; P=0.035), and the λHU in VP (r=0.216; P=0.043). SDCT parameter values showed no statistical difference between negative and positive expression in HER2 (all P values >0.05). There was no significant correlation between SDCT parameters and the expression of HER2 in CRAC (all P values >0.05). The quantitative parameters of SDCT in the VP provide valuable information for distinguishing between the low expression and high expression of Ki-67 in CRAC.

Immunohistochemical analysis of Tn antigen expression in colorectal adenocarcinoma and precursor lesions

BackgroundThe Tn antigen (CD175) is an O-glycan expressed in various types of human adenocarcinomas, including colorectal cancer (CRC), though prior studies have relied heavily upon poorly characterized in-house generated antibodies and lectins. In this study, we explored Tn expression in CRC using ReBaGs6, a well-characterized recombinant murine antibody with high specificity for clustered Tn antigen.MethodsUsing well-defined monoclonal antibodies, expression patterns of Tn and sialylated Tn (STn) antigens were characterized by immunostaining in CRC, in matched peritumoral [transitional margin (TM)] mucosa, and in normal colonic mucosa distant from the tumor, as well as in adenomas. Vicia villosa agglutinin lectin was used to detect terminal GalNAc expression. Histo-scoring (H scoring) of staining was carried out, and pairwise comparisons of staining levels between tissue types were performed using paired samples Wilcoxon rank sum tests, with statistical significance set at 0.05.ResultsWhile minimal intracellular Tn staining was seen in normal mucosa, significantly higher expression was observed in both TM mucosa (p < 0.001) and adenocarcinoma (p < 0.001). This pattern was reflected to a lesser degree by STn expression in these tissue types. Interestingly, TM mucosa demonstrates a Tn expression level even higher than that of the adenocarcinoma itself (p = 0.019). Colorectal adenomas demonstrated greater Tn and STn expression relative to normal mucosa (p < 0.001 and p = 0.012, respectively).ConclusionsIn summary, CRC is characterized by alterations in Tn/STn antigen expression in neoplastic epithelium as well as peritumoral benign mucosa. Tn/STn antigens are seldom expressed in normal mucosa. This suggests that TM mucosa, in addition to CRC itself, represents a source of glycoproteins rich in Tn that may offer future biomarker targets.

PD-L1 Expression in Colorectal Adenocarcinoma Is Associated With the Tumor Immune Microenvironment and Epithelial-Mesenchymal Transition.

Colorectal carcinomas are the third-most common tumors in the world, and colorectal cancer ranks second in cancer-related deaths. Our aim in this study was to investigate the correlation between programmed cell death ligand 1 (PD-L1) expression and clinicopathologic parameters in colorectal carcinomas and their relationship to the tumor immune microenvironment, epithelial-mesenchymal transition (EMT), and microsatellite instability. We also investigated the predictive and prognostic role of PD-L1. One hundred patients with a diagnosis of colorectal adenocarcinoma who did not receive neoadjuvant therapy were included in the study. The relationships among the altered expression of PD-L1; vimentin; E-cadherin; mismatch repair status; and pathologic microenvironmental features, including the presence of tumor budding and CD8-positive tumor infiltrating lymphocytes (TILs), were assessed. Increased PD-L1 expression in tumor cells was associated with increased TILs (P = .013), high histologic grade (P = .011), advanced pathologic T stage (P = .007), lymph node metastasis (P = .002), distant metastasis (P < .001), perineural invasion (P = .009), high bud score (P = .023), EMT (P < .001), and shorter disease-free survival (P = .029). Overall, PD-L1 expression in colorectal carcinoma tumor cells is a marker of poor prognosis, and the positive correlation detected between EMT status and PD-L1 expression suggests that patients with the mesenchymal phenotype may be more likely to benefit from programmed cell death 1 protein/PD-L1 immunotherapy.

Significance of CXCL9 and Vascular endothelial growth factor-α (VEGF-α) expression in Colorectal adenocarcinoma :(Immunohistochemical Study)

Significance of CXCL9 and Vascular endothelial growth factor-α (VEGF-α) expression in Colorectal adenocarcinoma :(Immunohistochemical Study)

Effects of hsa-mir-145-5p on the Regulation of msln Expression in Colorectal Adenocarcinoma.

Colorectal cancer (CRC) is one of the most common gastrointestinal cancers in the world, and its incidence is increasing all over the world including China. In recent years, research data show that some miRNAs are differentially expressed in cancer tissues, and their expression is closely contributed with the prognosis of CRC. Microarray technology was used, and 179 miRNAs were screened out with significantly altered expression in CRC tissues compared with adjacent tissues. The expression of mir-145-5p in tumor tissues was 3.48 times lower than that in normal tissues. Using bioinformatics technology and network resource prediction, we found that mir-145-5p had a potential target gene relationship with msln gene. Then, qRT-PCR was used to validate the expression level of mir-145-5p and msln mRNA in CRC and paracancerous tissues. The results showed that msln mRNA was higher than in normal tissues, while mir-145-5p was lower, with statistically significant difference (P < 0.01, n = 3). Furthermore, the expression of msln protein in CRC and normal colorectal tissues was detected by protein mass spectrometry (MRM) (n = 3) and immunohistochemistry in a total case of 30 colorectal cancer tissues and normal tissues. Result showed that the positive expression of msln in CRC was higher than that in normal colorectal tissues, 1.38e-6 and 1.89e-6, respectively (P < 0.01, n = 3). Furthermore, in 48 h RTCA real-time monitoring experiment, mir-145-5p showed inhibitory effect on the proliferation of colo320 cells stimulated by msln. This study demonstrated that msln is a target gene of mir-145-5p in CRC. Besides, mir-145-5p negatively regulates the proliferation of CRC colo320 cells through downregulating msln gene expression in CRC colo320 cells.

Tissue Factor Expression in Colorectal Adenocarcinoma: Association with Angiogenesis and Clinical and Pathological Aspects

Abstract Introduction Tissue factor (TF) expression has been described in various neoplasms and was correlated with angiogenesis and metastases. Objectives To describe TF expression in colorectal cancers, correlating it with microvessel density and clinical and pathological variables. Methods Immunohistochemistry was used to determine TF expression and microvessel density. The Student t-test was used to compare high and low TF expression with microvessel density and with age. The chi-squared test was used for other comparisons, and Kaplan-Meier curves were used for survival analyses. Results Forty-three patients were operated with curative intent. Their mean age was 58.1 ± 12.6 years old, and 62.8% were male. The rectum was the most common location (60,4%), and most tumors reached the serosa and peri-intestinal fat (72.1%). Lymph nodes were positive in 46.5%, and 72.1% of the tumors were moderately differentiated adenocarcinomas. Death occurred in 27.6 ± 12.8 months in 51.1% of the patients who had recurrence. Tissue factor expression was intense in 88.4%. There was a positive correlation between TF expression and microvessel density (p = 0.02), and between TF and older age (p &lt; 0.01). There was no correlation between TF expression and other variables (gender, histological type, penetration into the intestinal wall, and lymphatic and systemic metastases). Tissue factor expression did not correlate with survival. Conclusion Tissue factor expression correlated with increased microvessel density and older age. Further studies are necessary to ascertain the clinical relevance of TF in colorectal cancer.

The Association of VEGF Expression with Degree of Differentiation and Lymphovascular Invasion in Colorectal Adenocarcinoma

BackgroundColorectal carcinoma is the third most common malignancy in the world. Colorectal carcinoma is a heterogeneous tumor withdifferent clinical pathologic features and prognostic values. For the same tumor-stage, patients could have difference prognosis andit has been suggested that the angiogenesis might be correlated with the prognosis, especially expression of vascular endothelialgrowth factor (VEGF) as the main pro-angiogenic factor. High VEGF expression in colorectal adenocarcinoma is associated withincreased blood vessels in invasive tumor area, cell proliferation and metastases. However, relation VEGF expression with thedegree of differentiation and lymphovascular invasion is not known.MethodsThis was a retrospective observational study with cross sectional approach. Samples were obtained from 39 paraffin blocks withdiagnosis adenocarcinoma not otherwise specific (NOS) in four Anatomical Pathology Laboratory in West Sumatera 2018 andevaluated for degree of differentiation and lymphovascular invasion. VEGF expressions in tumor cell were analyzed usingimmunohistochemistry staining. Bivariate statistical analysis used Fisher's Exact test and value p&lt;0.05 was considered significant.ResultsColorectal adenocarcinoma with high grade differentiation entirely had high VEGF expression (100%), while low gradedifferantiation with high VEGF expression was 60.7%. Lymphovascular invasion positive was mostly found with high VEGFexpression (80.6%). Statistical analysis showed significant association between VEGF expression with degree of differentiation(p=0.017) and lymphovascular invasion (p=0.028).ConclusionThe conclusion was VEGF expression had significant association with degree of differentiation and lymphovascular invasion ofcolorectal adenocarcinoma.

The significance of Aldehyde dehydrogenase 1A1 expression in colorectal carcinoma

Background: Colorectal carcinoma (CRC) is the third most common cancer in the world constituting about 10% of all cancers. ALDH1A1 has been used as a stem cell marker, and plays important functional roles in stem cells. Expression of ALDH1A1 by cancer stem cells (CSCs) has been demonstrated in multiple types of cancers.Aim: This work aimed to evaluate ALDH1A1 expression in colorectal adenocarcinoma and determine the relation between ALDH1A1 expression and different clinico-pathological variables.Material and method: This is a selected retrospective study included 50 different cases of colorectal adenocarcinoma. ALDH1A1 immunostaining was performed for all cases.Results: There was a highly significant statistical difference between ALDH1A1 expression in studied cases according to tumor site, lymph node metastasis and TNM stage (P value

MiR-144-3p inhibited the growth, metastasis and epithelial-mesenchymal transition of colorectal adenocarcinoma by targeting ZEB1/2.

miR-144-3p is aberrantly expressed in several types of human cancer and functions as a tumor suppressor by inhibiting metastasis. However, the clinical significance and biological function of miR-144-3p in colorectal adenocarcinoma (CRA) have yet to be elucidated. Here we reported that miR-144-3p expression level was significantly down-regulated in CRA tissues compared with matched noncancerous colorectal mucosae tissues. Low miR-144-3p expression was correlated with adverse clinicopathologic characteristics and poor prognosis of CRA patients. Cox regression analysis showed that low miR-144-3p expression was an independent risk factor for DFS and OS in CRA. In vitro and in vivo assays showed that miR-144-3p significantly inhibited proliferation, migration and invasion of CRA cells. In particular, miR-144-3p could suppress EMT process of CRA cells by regulating the cytoskeleton and EMT markers. Bioinformatics analysis indicated that EMT associated transcription factors ZEB1 and ZEB2 were potential targets of miR-144-3p, and miR-144-3p inhibited ZEB1 and ZEB2 expression and was negatively correlated with their expression in CRA. Finally, we confirmed that ZEB1 and ZEB2 down-regulation collaboratively mediated the inhibitory effect of miR-144-3p on proliferation, invasion and EMT of CRA cells. In conclusion, our study provided evidence that miR-144-3p could inhibit CRA cell proliferation, invasion and EMT by targeting ZEB1/2.

Correlation of CD47 Expression with Adverse Clinicopathologic Features and an Unfavorable Prognosis in Colorectal Adenocarcinoma.

CD47, a transmembrane protein, is widely overexpressed on the tumor cell surface. However, the prognostic significance of CD47 expression in colorectal adenocarcinoma (CRA) has not yet been clarified. Here, we investigated the clinicopathologic significance of CD47 expression in CRA. CD47 expression was evaluated via immunohistochemical analysis of microarray sections of 328 CRA tissues. CD47 expression was observed in 53 (16.2%) of the 328 CRA tissues, and positive expression was associated with lymphatic invasion (p = 0.018), perineural invasion (p = 0.024), tumor budding (p = 0.009), the pathologic N stage (p = 0.022), and the American Joint Committee on Cancer (AJCC) stage (p = 0.027). In survival analyses of 329 patients, a positive CD47 expression was associated with a poor recurrence-free survival (RFS) (p = 0.032). In multivariate analysis, however, it was not an independent prognostic factor. In patients who underwent surgical resection without adjuvant treatment, a positive CD47 expression was associated with a shorter RFS (p = 0.001) but not with cancer-specific survival (CSS). In patients who received postoperative adjuvant treatment, no significant differences were found in both RFS and CSS. In conclusion, we investigated CD47 expression in 328 CRA tissues. A positive CD47 expression was observed in a minority (16.2%) of the tissues and was significantly associated with adverse clinicopathologic features and a poor patient outcome.

Lumican inhibits immune escape and carcinogenic pathways in colorectal adenocarcinoma.

Lumican (LUM), a small leucine-rich proteoglycan, is a component of the extracellular matrix. Abnormal LUM expression is potentially associated with cancer progression. In the present study, we confirmed high LUM mRNA expression in colorectal adenocarcinoma (COAD) through the UALCAN database. The Kaplan-Meier method, univariate, and multivariate COX analysis showed that high LUM expression is an independent determinant of poor prognosis in COAD. A COX regression model was constructed based on clinical information and LUM expression. The receiver operating characteristic (ROC) curve indicated that this model was highly accurate in monitoring COAD prognosis. The co-expression network of LUM was determined by LinkedOmics, which showed that LUM expression was closely related to immune escape and the miR200 family. Furthermore, we studied the co-expression network of LUM and found that LUM could promote tumor metastasis and invasion. The Tumor Immune Estimation Resource website showed that LUM was closely related to immune infiltration and correlated with regulatory T cells, tumour-associated macrophages, and dendritic cells. We found that LUM cultivated cancer progression by targeting the miR200 family to promote epithelial-to-mesenchymal transition. These findings suggest that LUM is a potential target for inhibiting immune escape and carcinogenic pathways.

Clinical significance of proliferation index and E-cadherin expression in colorectal adenocarcinoma

Introduction/Objective. The aim of this study is to examine the association of E-cadherin expression and high proliferation index (proIDX) with clinical and pathological indicators of colorectal cancer progression. Methods. The biopsy of 72 patients, obtained by resection of colorectal cancer, was routinely processed at the Institute of Pathology of the Clinical Centre of Montenegro, embedded in paraffin and archived. Based on the archived pathohistological reports, two study groups were formed: the first group (n = 72) consisted of operative biopsies of colorectal cancer, and the control group (n = 72) consisted of biopsies of adjacent non-tumor tissue. Routine hematoxylin-eosin and immunohistochemical avidin-biotin-peroxidase complex method with anti-Ki67 and anti-E-cadherin antibodies was applied on. After quantification of the results for statistical tests, the software package SPSS for Windows (19.0) was used. Results. In colorectal carcinoma, we observed a significant association of proIDX with pT stage, lymph and blood vessel invasion, perineural invasion, lymph node metastases and distant metastases, and Astler?Coller stage tumor disease. We also observed that the absence of E-cadherin was significantly associated with pT stage, lymph and blood vessel invasion, perineural invasion with lymph node metastases, distant metastases, with C2 and D Astler?Coller tumor stage. E-cadherin expression is associated with proIDX with a significantly high, negative correlation coefficient. Conclusion. Our results indicate that it is possible to differentiate patients into groups with a higher or lower risk of developing metastatic disease, based on the expression of Ki67 and E-cadherin.

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.

Heat shock protein beta 3 (HSPB3) is an unfavorable molecular biomarker in colorectal adenocarcinoma.

Small heat shock proteins (sHSPs) participate in numerous cellular functions including cell signaling, differentiation, and apoptosis. Deregulation of the physiological expression level of sHSPs has been associated with several malignancies. Heat shock protein beta 3 (HSPB3) is the third member of the sHSP family in human and is mainly expressed in skeletal and smooth muscles. In this study, we investigated the potential prognostic significance of HSPB3 expression in colorectal adenocarcinoma, the most frequent type of colorectal cancer. For this purpose, we isolated total RNA from 188 colorectal adenocarcinoma specimens and 68 paired noncancerous ones. After reverse transcription of 2 μg total RNA, we quantified HSPB3 levels by using an in-house-developed real-time quantitative polymerase chain reaction method, based on the SYBR Green chemistry. Comparison of HSPB3 levels among 68 pairs of colorectal tumors and their adjacent noncancerous mucosae uncovered the downregulation of HSPB3 expression in the majority of malignant colorectal tumors. More importantly, high HSPB3 expression is associated with poor relapse-free survival (RFS) and overall survival (OS) of patients with colorectal adenocarcinoma. Multivariable Cox regression analysis revealed that HSPB3 overexpression could serve as an adverse prognostic biomarker in colorectal adenocarcinoma, independent of tumor location, histological grade, and TNM stage. Patients' stratification according to tumor location, histological grade, and TNM stage revealed that high HSPB3 messenger RNA expression retains its unfavorable prognostic potential regarding OS, in particular groups of patients with substantially different prognosis. In conclusion, high HSPB3 expression is associated with poor RFS and OS of patients with colorectal adenocarcioma, independently of clinicopathological prognosticators.

Immunohistochemical study of VEGF-A, VEGFR-1, VEGFR-2 and CD34 expression in сolorectal adenocarcinoma progression

Aim – to study VEGF-A, VEGFR-1, VEGFR-2 and CD34 immunohistochemical expression on the I, II, III, IV stages (pTNM) of colorectal adenocarcinoma development.Materials and methods. Pathomorphological and immunohistochemical studies of surgical material of colorectal adenocarcinoma (CRA) from 40 patients (I, II, III and IV stages, 10 cases in each group) were conducted.Results. There is a tendency to increasing expression of VEGF-A and VEGFR-2 during the CRA progression from I to IV stage (VEGF-A 37.80 (30.22; 56.89) CUOD on I stage, 88.50 (63.00 ; 115.00) CUOD on II stage, 79.34 (63.14; 84.99) CUOD on III stage, 84.69 (80.66; 110.28) CUOD on IV stage; VEGFR-2 – 52.75 (39.14; 70.22) CUOD on I stage, 82.71 (63.14; 111.19) CUOD on II stage, 104.17 (96.04; 111.02) CUOD on III stage, 99.91 (86.15; 120.29) CUOD on IV stage). The expression indices of these markers correlate in CRA stages I, II and III (r = 0.95, r = 0.69, r = 0.85). It is established that VEGFR-1 is not expressed in unchanged mucous membrane of the large intestine, as well as in samples of CRA stage I. On subsequent II, III and IV stages of CRA progresson the marker is expressed by stromal cells, but there is an absence of statistically significant difference between the expression indices. There are no correlations between expression indices of VEGFR-1 and other studied markers. The microvascular density assessed by CD34 expression is not significantly different on each of CRA progression stages. There are direct correlations between microvascular density and VEGF-A expression (r = 0.70), and VEGFR-2 expression (r = 0.69) in CRA III stage, microvascular density and VEGF-A expression in CRA IV stage (r = 0.69).Conclusions. Expression of VEGF-A and VEGFR-2 increases with the progression of colorectal adenocarcinoma from stage I to stage IV, with a maximum “jump” of the expression levels from stage I to stage II of colorectal adenocarcinoma, which may be due to abnormally increasing KRAS activity.

Mesothelin expression and its prognostic role according to microsatellite instability status in colorectal adenocarcinoma.

The cell-surface glycoprotein, mesothelin, is normally present on mesothelial cells. Overexpression of mesothelin has been reported in many tumors and is correlated with poor outcome. We investigated the clinicopathologic significance of mesothelin expression in colorectal adenocarcinoma with microsatellites instability (MSI) status.Mesothelin expression was evaluated immunohistochemically in tissue microarray blocks from 390 colorectal adenocarcinoma samples. Mesothelin expression was interpreted according to the intensity and extent. A score of 2 was considered high expression. We analyzed the correlation between mesothelin expression and clinicopathologic characteristics.High mesothelin expression was observed in 177 (45.4%) out of 390 colorectal adenocarcinoma samples and was significantly associated with high histologic grade (P = .037), lymphatic invasion (P = .028), lymph node metastasis (P = .028), and high AJCC stage (P = .026). Kaplan-Meier survival curves revealed no significant difference between patients with high mesothelin expression and patients with low mesothelin expression in both recurrence-free survival (RFS) and cancer-specific survival (P = .609 and P = .167, respectively). In subgroup survival analyses, high mesothelin expression was associated with poor RFS in the MSI-High group of colorectal adenocarcinoma (P = .004).High mesothelin expression was significantly associated with aggressive phenotypes and poor patient outcome in MSI-High colorectal adenocarcinoma.

Altered miR-21, miRNA-148a Expression in Relation to KRAS Mutation Status as Indicator of Adenoma-Carcinoma Transitional Pattern in Colorectal Adenoma and Carcinoma Lesions.

Sporadic colorectal cancer (CRC) is a fatal disease, mostly known as the silent killer, due to the fact that this disease is asymptomatic before diagnosis in advanced stage. Screening and the early detection of CRC and colorectal adenoma (CRA) by non-aggressive molecular biomarkers' signature is useful for improvement of survival rate in CRC patients. To achieve such a goal, a better understanding of distinct molecular abnormalities as candidate biomarkers in CRC development is crucial. In this study, seventy-five archived FFPE CRC samples, including colorectal adenocarcinoma, adenomatous polyps (adenoma), and adjacent non-neoplastic mucosa were collected for the investigation by Sanger sequencing at the DNA level and by real-time PCR at the RNA level. The results of the KRAS mutational analysis have shown that the majority of somatic mutations in the KRAS affect only one codon, mainly codon 12(p.G12D) with low frequency in adenomas (13.3%) versus CRCs (36%). The results of dysregulated epigenetic changes of miR-21 clearly showed upregulation of expression in colorectal adenocarcinoma, compared to non-neoplastic mucosa, in colorectal adenoma vs non-neoplastic mucosa: (p < 0.001) and in CRC versus adenoma (p < 0.001); while miR-148a expression were significantly downregulated in CRC, compared to non-neoplastic mucosa, in colorectal adenoma vs non-neoplastic mucosa, and in adenoma vs CRC (p < 0.001). Our findings support the important role of miR-21 in stages I-II of CRC, and the KRAS G12D mutant, and differential miR-148a expression, in advanced stages of CRC.

The Effects of Cytotoxic Dose of Testosterone on Bax , Bcl2, and CD82/KAI1 Genes Expression in Colorectal Adenocarcinoma (HT29) and Brain Glioblastoma Cells(A172)

The Effects of Cytotoxic Dose of Testosterone on Bax , Bcl2, and CD82/KAI1 Genes Expression in Colorectal Adenocarcinoma (HT29) and Brain Glioblastoma Cells(A172)

Expression of p-AMPK in colorectal cancer revealed substantial diverse survival patterns.

Objective:Several cancers have showed differences in the role of p- AMPK in cancer growth, progression and prognosis, and little is identified regarding the significance of p-AMPK expression in colorectal adenocarcinoma. Therefore, this report will define p-AMPK phenotype in a panel of colorectal carcinomas and explore the relationship between this phenotype and tumor clinicopathological features.Methods:A total of 228 cases comprising 155 large intestine cancers and 73 controls (40 benign tumors and thirty three non-cancerous tissues) were employed in tissue microarray construction. Immunohistochemistry (IHC) staining was applied to reveal p-AMPK expression. This study was carried out in the pathology lab of King Abdulaziz University Hospital over a duration of 15 months and was completed on 7th July 2018.Results:Phosphorylated AMPK was identified in 133 (85.8%) of colorectal cancers and 73 (100%) control cases. Histologic type was noticeably correlated with p-AMPK immunostaining (P= 0.001), high score of p-AMPK immunostaining is more frequent in control cases. Considerable varied survival models were observed with neoplasm size, metastatic tumor, recurrence and disease relapse (P-values<0.01). Survival estimates are considerably healthier in positive cases which have one of the following features size less than 5 cm, absence of metastatic tumor, no reoccurrence or disease relapse.Conclusions:The present study showed a reduction in the IHC staining of p-AMPK in colorectal cancer compared with controls. IHC staining of p-AMPK can be a supportive marker in predicting prognosis and survival estimates of colorectal tumors with specific clinical factors.