scholarly journals Interplay of stromal tumor-infiltrating lymphocytes, normal colonic mucosa, cancer-associated fibroblasts, clinicopathological data and the immunoregulatory molecules of patients diagnosed with colorectal cancer

2021 ◽  
Author(s):  
Łukasz Zadka ◽  
Mariusz Chabowski ◽  
Damian Grybowski ◽  
Aleksandra Piotrowska ◽  
Piotr Dzięgiel
Keyword(s):  
Colorectal Cancer ◽  
Negative Correlation ◽  
Colonic Mucosa ◽  
Tnm Classification ◽  
Stage Iv ◽  
Tumor Infiltrating Lymphocytes ◽  
Tumor Stroma ◽  
Lymphocytic Infiltration ◽  
Normal Colonic Mucosa ◽  
Ki 67

AbstractA total of 94 patients with colorectal cancer (CRC) were included in this study. Lymphocytic infiltration of CD45+ cells in the normal colon was more pronounced than that in the paired tumor stroma (p = 0.0008). The mean immunoscore of CD45+TILs was decreased in CRC compared with the controls (p = 0.0010). The percentage of CD3+ cells was higher in stage II than in stage IV (p = 0.0218) and showed a negative correlation with the TNM classification (r = -0.2867, p = 0.0109). The number of stromal CD4+TILs was higher in stage I than in stage III (p = 0.0116) and IV (p = 0.0104), and there was a negative correlation between this number and the stage (r = -0.3708, p = 0.0008). There was a positive correlation between the Ki-67 and CD45+ (r = 0.2468, p = 0.0294), CD3+ (r = 0.3822, p = 0.0006), and CD4+ cells (r = 0.5465, p < 0.0001). The levels of cancer-associated fibroblast (CAF) markers such as α-SMA, thrombin and fibronectin were significantly higher in CRC than in normal colonic mucosa. The immunohistochemical expression of α-SMA was negatively correlated with TILs, while fibronectin showed positive coexpression. A higher number of cells expressing IL-2Rα, PD-L1, CD33 and CD14 were found in colorectal adenocarcinomas than in controls. The number of CD14+ cells was also dependent on the TNM stage (p = 0.0444) and tumor budding (p = 0.0324). These findings suggest a suppressive impact of CRC on the adaptive immune response and emphasize the importance of CAFs in regulating tumor immunity.

Tumor-Infiltrating FOXP3+ T Regulatory Cells Show Strong Prognostic Significance in Colorectal Cancer

2009 ◽  
Vol 27 (2) ◽  
pp. 186-192 ◽  
Author(s):  
Paul Salama ◽  
Michael Phillips ◽  
Fabienne Grieu ◽  
Melinda Morris ◽  
Nik Zeps ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colonic Mucosa ◽  
Tumor Tissue ◽  
Early Stage ◽  
Prognostic Significance ◽  
High Density ◽  
Prognostic Indicators ◽  
Normal Colonic Mucosa ◽  
Solid Cancer ◽  
Histopathologic Features

Purpose To determine the prognostic significance of FOXP3+ lymphocyte (Treg) density in colorectal cancer compared with conventional histopathologic features and with CD8+ and CD45RO+ lymphocyte densities. Patients and Methods Tissue microarrays and immunohistochemistry were used to assess the densities of CD8+, CD45RO+, and FOXP3+ lymphocytes in tumor tissue and normal colonic mucosa from 967 stage II and stage III colorectal cancers. These were evaluated for associations with histopathologic features and patient survival. Results FOXP3+ Treg density was higher in tumor tissue compared with normal colonic mucosa, whereas CD8+ and CD45RO+ cell densities were lower. FOXP3+ Tregs were not associated with any histopathologic features, with the exception of tumor stage. Multivariate analysis showed that stage, vascular invasion, and FOXP3+ Treg density in normal and tumor tissue were independent prognostic indicators, but not CD8+ and CD45RO+. High FOXP3+ Treg density in normal mucosa was associated with worse prognosis (hazard ratio [HR] = 1.51; 95% CI, 1.07 to 2.13; P = .019). In contrast, a high density of FOXP3+ Tregs in tumor tissue was associated with improved survival (HR = 0.54; 95% CI, 0.38 to 0.77; P = .001). Conclusion FOXP3+ Treg density in normal and tumor tissue had stronger prognostic significance in colorectal cancer compared with CD8+ and CD45RO+ lymphocytes. The finding of improved survival associated with a high density of tumor-infiltrating FOXP3+ Tregs in colorectal cancer contrasts with several other solid cancer types. The inclusion of FOXP3+ Treg density may help to improve the prognostication of early-stage colorectal cancer.

The different immune profiles of normal colonic mucosa in cancer-free Lynch syndrome carriers and Lynch syndrome colorectal cancer patients

2021 ◽  
Author(s):  
Lena Bohaumilitzky ◽  
Klaus Kluck ◽  
Robert Hüneburg ◽  
Richard Gallon ◽  
Jacob Nattermann ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Cancer Patients ◽  
Colonic Mucosa ◽  
Normal Colonic Mucosa ◽  
Colorectal Cancer Patients

Antioxidant Agents and Colorectal Carcinogenesis: Role of β-Carotene, Vitamin E and Vitamin C

1996 ◽  
Vol 82 (1) ◽  
pp. 6-11 ◽  
Author(s):  
Giuseppe Pappalardo ◽  
Antonio Guadalaxara ◽  
Giuseppe Maiani ◽  
Giovanni Illomei ◽  
Mauro Trifero ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Vitamin E ◽  
Vitamin C ◽  
Colonic Mucosa ◽  
Genetic Alterations ◽  
Colorectal Carcinogenesis ◽  
Normal Colonic Mucosa ◽  
Antioxidant Agents ◽  
Β Carotene

In consideration of findings reported in the literature and of our study, we examined the correlation between antioxidants (β-carotene, vitamin C, vitamin E) and colorectal carcinogenesis. Although diagnostic progress has been made in the last decades, no significant improvements in death rates have been achieved in the western world. Exogenous factors might be responsible for a complex alteration process of normal colonic mucosa into adenoma and carcinoma. Free radicals and reactive oxygen metabolites, due to increased production or to reduced inactivation, following a decrease in the antioxidant burden in the mucosa, might cause damage to DNA, thereby resulting in genetic alterations. This might represent the cause of the transformation process: normal mucosa→ adenoma→ carcinoma. In a prospective study, we observed a reduction of β-carotene levels in normal colonic mucosa in patients with polyps and colorectal cancer. We also showed that β-carotene supplementation raises levels of this micronutrient in the colonic mucosa of these patients. Findings from the literature and our trials show a significant decrease in the antioxidant capacity of colorectal mucosa in patients affected by colorectal cancer, although there is a significant interindividual variability. Such results suggest a possible chemopreventive role of antioxidant agents in colorectal cancer.

scholarly journals An Assessment of Database-Validated microRNA Target Genes in Normal Colonic Mucosa: Implications for Pathway Analysis

2017 ◽  
Vol 16 ◽  
pp. 117693511771640 ◽  
Author(s):  
Martha L Slattery ◽  
Jennifer S Herrick ◽  
John R Stevens ◽  
Roger K Wolff ◽  
Lila E Mullany
Keyword(s):  
Colorectal Cancer ◽  
Mrna Expression ◽  
Messenger Rna ◽  
Colonic Mucosa ◽  
Target Gene ◽  
Target Genes ◽  
Multiple Comparisons ◽  
Normal Colonic Mucosa ◽  
Seed Region ◽  
Discovery Phase

Background: Determination of functional pathways regulated by microRNAs (miRNAs), while an essential step in developing therapeutics, is challenging. Some miRNAs have been studied extensively; others have limited information. In this study, we focus on 254 miRNAs previously identified as being associated with colorectal cancer and their database-identified validated target genes. Methods: We use RNA-Seq data to evaluate messenger RNA (mRNA) expression for 157 subjects who also had miRNA expression data. In the replication phase of the study, we replicated associations between 254 miRNAs associated with colorectal cancer and mRNA expression of database-identified target genes in normal colonic mucosa. In the discovery phase of the study, we evaluated expression of 18 miRNAs (those with 20 or fewer database-identified target genes along with miR-21-5p, miR-215-5p, and miR-124-3p which have more than 500 database-identified target genes) with expression of 17 434 mRNAs to identify new targets in colon tissue. Seed region matches between miRNA and newly identified targeted mRNA were used to help determine direct miRNA-mRNA associations. Results: From the replication of the 121 miRNAs that had at least 1 database-identified target gene using mRNA expression methods, 97.9% were expressed in normal colonic mucosa. Of the 8622 target miRNA-mRNA associations identified in the database, 2658 (30.2%) were associated with gene expression in normal colonic mucosa after adjusting for multiple comparisons. Of the 133 miRNAs with database-identified target genes by non-mRNA expression methods, 97.2% were expressed in normal colonic mucosa. After adjustment for multiple comparisons, 2416 miRNA-mRNA associations remained significant (19.8%). Results from the discovery phase based on detailed examination of 18 miRNAs identified more than 80 000 miRNA-mRNA associations that had not previously linked to the miRNA. Of these miRNA-mRNA associations, 15.6% and 14.8% had seed matches for CRCh38 and CRCh37, respectively. Conclusions: Our data suggest that miRNA target gene databases are incomplete; pathways derived from these databases have similar deficiencies. Although we know a lot about several miRNAs, little is known about other miRNAs in terms of their targeted genes. We encourage others to use their data to continue to further identify and validate miRNA-targeted genes.

MGMT methylation is associated primarily with the germline C>T SNP (rs16906252) in colorectal cancer and normal colonic mucosa

2009 ◽  
Vol 22 (12) ◽  
pp. 1588-1599 ◽  
Author(s):  
Nicholas J Hawkins ◽  
James H-F Lee ◽  
Justin J-L Wong ◽  
Chau-To Kwok ◽  
Robyn L Ward ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colonic Mucosa ◽  
Normal Colonic Mucosa ◽  
Mgmt Methylation

scholarly journals Comparative analysis of exosome markers and extracellular vesicles between colorectal cancer and cancer-associated normal colonic mucosa

2020 ◽  
Author(s):  
Łukasz Zadka ◽  
Aleksandra Piotrowska ◽  
Agnieszka Opalińska ◽  
Katarzyna Haczkiewicz-Leśniak ◽  
Damian Grybowski ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Comparative Analysis ◽  
Extracellular Vesicles ◽  
Colonic Mucosa ◽  
Normal Colonic Mucosa

scholarly journals Histopathological finding as a prognostic factor of the surgical treatment outcome in colorectal cancer

2010 ◽  
Vol 67 (8) ◽  
pp. 638-643 ◽  
Author(s):  
Svetozar Secen ◽  
Nebojsa Moljevic ◽  
Milivoje Vukovic ◽  
Ljiljana Somer
Keyword(s):  
Colorectal Cancer ◽  
Treatment Outcome ◽  
Prognostic Factors ◽  
Surgical Treatment ◽  
Tnm Classification ◽  
Stage Iv ◽  
Histological Structure ◽  
Poorly Differentiated ◽  
The Impact ◽  
Stage D

Background/Aim. Adenocarcinomas of the colon are the most common malignant colorectal tumors. Macroscopic and histopahtological features of colorectal cancer significantly affect its outcome. The aim of this study was to analyze the impact of histopahological finding as a prognostic factor on the surgical treatment outcome and the course of the disease. Methods. In the first part of this study the distribution (numerical and proportional) of certain histopathological parameters in the examined groups of patients were reviewed; in the second part of the study the statistical significance of the impact of the certain elements of a histopahtological finding on the surgical treratment outcome was analyzed. The histopathological elements analyzed included: the hsitological tumor type grading according to Duke, ie Astler-Coller, and tumor, nodes, metastases (TNM) staging in the examined sample of 100 patients. Results. Statistically significant prognostic factors of the outcome of surgical treatment were selected after multivariant analysis. These factors comprise Astler-Coller-Dukes stage D (revealed in 77.78% patients died), stage IV according TNM classification (T1-4, N0-2, M1), histological structure (poorly diferentiated adenocarcinoma in 85.2% patents died) and type of tumor (mucynous adenocarcinoma was more often present in died, 77.78%). Since ? = 0.000 for four risk factors were formed using discriminant analysus, it was proved their significant influence on the outcome of surgical treatment. Discriminant coefficient showed that the greatest influence on surgical treatment were registred in patients with tumor of Astler-Coller-Dukes stage D (0.255), poorly differentiated adenocarcinoma (histological structure) (0.139), mucynous adenocarcinoma (type of tumor) (0.074) and stage IV according to the TNM elassification (T1-4, N0-2, M1) (0.39). Conclusion. The prognostic factors influencing the outcome of surgery for colorectal carcinoma were defined. Patients with pathohistological finding of Astler-Coller-Dukes stage D, stage IV according to the TNM classification (T1-4, N0-2, M1) and poorly differentiated adenocarcioma have statistically highly significant mortality during the perioperative course of the disease.

197P Tumor-infiltrating lymphocytes predict the chemotherapeutic outcomes in patients with stage IV colorectal cancer

2016 ◽  
Vol 27 (suppl_9) ◽  
Author(s):  
M. Shibutani ◽  
K. Maeda ◽  
H. Nagahara ◽  
T. Fukuoka ◽  
Y. Iseki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stage Iv ◽  
Tumor Infiltrating Lymphocytes ◽  
Stage Iv Colorectal Cancer ◽  
Infiltrating Lymphocytes
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