scholarly journals Anti-cytokeratin 7: a positive marker for epithelial dysplasia in flat bowel mucosa

2004 ◽  
Vol 4 (3) ◽  
pp. 24-30 ◽  
Author(s):  
Svjetlana Radović ◽  
Ivan Selak ◽  
Mirsad Babić ◽  
Zora Vukobrat-Bijedić ◽  
Željka Knežević
Keyword(s):  
Colonic Mucosa ◽  
Staining Intensity ◽  
Normal Mucosa ◽  
Epithelial Dysplasia ◽  
Normal Colonic Mucosa ◽  
Severe Dysplasia ◽  
Cytokeratin 7 ◽  
Biopsy Specimens ◽  
Keratin 7 ◽  
Bowel Mucosa

The aim of this paper is to establish by immunohistochemistry the expression of keratin 7 in inflammatory-regenerative flat bowel mucosa and in different grades of epithelial dysplasia regarding the sub-units expressed in normal and carcinomatous colonic mucosa. Biopsy specimens from 270 patients were examined: 74 were classified as inflammatory-regenerative changes and 196 as dysplastic lesions. There were 108 cases of mild dysplasia, 58 cases of moderate and 30 cases of severe dysplasia, respectively). Demonstration of location and intensity of cytokeratin 7 staining was performed by immunohistochemistry using monoclonal antibody (anti-cytokeratin 7). Findings of cytokeratin 7 in dysplastic lesions were compared with those in normal mucosa, inflammatory -regenerative mucosa and adenocarcinoma. Cytokeratin 7 is not found in normal colonic mucosa. In inflammatory-regenerative mucosa it was found in solitary cells in small number of cases. It is found in all cases of epithelial dysplasia and its expression showed no difference regarding moderate and severe dysplasia. In few cases of adenocarcinoma, cytokeratin 7 is found in traces and showed minimal staining intensity. Having in mind that cytokeratine 7 is primarily found in dysplastic lesions of the flat colonic mucosa it can be a valuable diagnostic tool in the histological interpretation of epithelial dysplasia.

scholarly journals Type IV collagen immunoreactivity of basement membrane in inflammatory-regenerative and dysplastic lesions of the flat colonic mucosa

2003 ◽  
Vol 3 (1) ◽  
pp. 30-35
Author(s):  
Svjetlana Radović ◽  
Ivan Selak ◽  
Mirsad Babić ◽  
Željka Knežević ◽  
Zora Vukobrat-Bijedić
Keyword(s):  
Basement Membrane ◽  
Colon Adenocarcinoma ◽  
Normal Mucosa ◽  
Collagen Iv ◽  
Epithelial Dysplasia ◽  
Collagen Type Iv ◽  
Severe Dysplasia ◽  
Colon Mucosa ◽  
Mild Dysplasia ◽  
Type Iv

The aim of this research is to establish by immunohistochemistry if there is a change in the expression of collagen type IV, as a substitute of basement membrane, in development of epithelial dysplasia in chronically inflamed colon mucosa.Methods. Biopsy specimens from 270 patients were examined: 74 were classified as inflammatory-regenerative and 196 as dysplastic lesions. There were 108 cases of mild dysplasia, 58 cases of moderate and 30 cases severe dysplasia, respectively. Visualisation of collagen IV and its way of expression within basement membrane of glandular crypts was performed by immunohistochemistry and then compared with findings in normal colon mucosa and colon adenocarcinoma tissue.Results. Changes in the expression of collagen IV comprised of its focal irregularities, diffuse thinning and/or thickening, focal interruptions or its complete absence. Significant changes in the expression of collagen IV in relation to normal mucosa already occur in inflammatory-regenerative mucosa. In mild dysplasia, these changes are more intensive in relation to those in inflammatory altered mucosa as well as at severe dysplasia in relation to moderate dysplasia. Changes in the expression of collagen IV in severe dysplasia are significantly more serious than in moderate dysplasia but are identical to those in colon adenocarcinoma tissue.Conclusion. These findings suggest that change in the expression of collagen IV is in correlation to a degree of epithelial dysplasia that developed in flat chronically inflamed colon mucosa.

Systemic administration of recombinant interferon alfa in carcinoma patients upregulates the expression of the carcinoma-associated antigens tumor-associated glycoprotein-72 and carcinoembryonic antigen.

1996 ◽  
Vol 14 (7) ◽  
pp. 2031-2042 ◽  
Author(s):  
M Roselli ◽  
F Guadagni ◽  
O Buonomo ◽  
A Belardi ◽  
V Vittorini ◽  
...  
Keyword(s):  
Carcinoembryonic Antigen ◽  
Tumor Cells ◽  
Colonic Mucosa ◽  
Antigen Expression ◽  
Staining Intensity ◽  
Normal Colonic Mucosa ◽  
Recombinant Interferon ◽  
Ifn Alpha ◽  
Important Approach ◽  
Tumor Biopsies

PURPOSE The ability of interferons (IFNs) to enhance tumor-associated antigen expression may be an important approach to enhance the efficacy of some monoclonal antibody (MAb)-based protocols for tumor diagnosis and/or therapy. The present study was designed to determine whether systemic IFN alpha-2a administration (via the intramuscular [IM] route) could upregulate the expression of tumor-associated glycoprotein-72 (TAG-72) and/or carcinoembryonic antigen (CEA) at histologically confirmed sites of carcinoma. PATIENTS AND METHODS Eighteen patients diagnosed with gastrointestinal (GI) carcinoma received systemic IFN alpha-2a according to four dose schedules. In cohorts I and II, patients received two injections of 3 or 6 x 10(6) U IFN alpha-2a per injection, respectively. Patients in cohorts III and IV received the same doses of IFN alpha-2a, 3 and 6 x 10(6) U, respectively, but three injections were given. Tumor and normal colonic mucosa biopsies were obtained from each patient by endoscopy before IFN alpha-2a and after IFN alpha-2a at surgery. The levels of TAG-72 and CEA expression were measured by (1) immunohistochemistry and reported as percent antigen-positive tumor cells, as well as the relative staining intensity, and (2) a quantitative radioimmunoassay. RESULTS TAG-72 and CEA levels were consistently increased in tumor biopsies taken from patients in cohorts III and IV. For example, of 10 patients treated in cohorts III and IV, eight had enhanced TAG-72 expression when measured either as percentage TAG-72-positive tumor cells or as an increased MAb staining intensity following IFN alpha-2a. CEA expression in tumor biopsies from seven of 10 patients in cohorts III and IV was also elevated following IFN alpha-2a treatment. Quantitative analysis of TAG-72 and CEA levels in tumor biopsies confirmed higher tumor antigen levels following IFN alpha-2a administration. No such increases in TAG-72 or CEA levels were observed in tumor samples taken from patients in cohorts I and II. CEA or TAG-72 expression in samples of histologically confirmed normal colonic mucosa showed little or no change after IFN alpha-2a treatment. CONCLUSION Systemic IFN alpha-2a administration can upregulate TAG-72 and CEA expression at distal tumor sites, which may play an important role in immunodiagnosis and therapy.

scholarly journals Colonic Stem Cells Expression of Lgr5 and CD133 Proteins as Predictive Markers in Colorectal Cancer among Egyptian Patients

2018 ◽  
Vol 6 (6) ◽  
pp. 968-974 ◽  
Author(s):  
Saed Rosiq ◽  
Olfat Hammam ◽  
Ahmed Abdelalim ◽  
Amgad Anas ◽  
Heba Khalil ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colonic Mucosa ◽  
Histological Grade ◽  
Normal Mucosa ◽  
Adenomatous Polyps ◽  
Stem Cell Marker ◽  
Control Group ◽  
Normal Colonic Mucosa ◽  
Depth Of Invasion ◽  
Group I

AIM: Colorectal cancer is the fourth common tumour in Egypt after lymphoid, breast and urinary tumours. The study aims to assess the expression of Lgr5 and CD133 in pre-malignant (adenomatous polyps and IBD), malignant colorectal lesions and normal colonic mucosa by immunohistochemical staining.MATERIAL AND METHODS: This prospective study was done on 100 patients presenting with colonic symptoms, patients were divided into four groups; group I including 20 patients in the control group, group II including 20 ulcerative colitis (U.C) patients, group III including 20 patients with adenomatous polyps and group IV including 40 patients with colorectal cancer (CRC).RESULTS: Lgr5 and CD133 expression was significantly higher in carcinoma than in adenomas, IBD and normal mucosa (P < 0.001). Lrg5 and CD133 was positively correlated with histological grade (P = 0.001), depth of invasion (P = 0.001), lymph node metastasis (P < 0.001), distant metastasis (P < 0.004) and TNM stage (P < 0.001).CONCLUSION: Role of Lgr5 and CD133 as stem cell marker was expressed and presented with different expression in the normal colonic mucosa, adenoma and CRC and showed increased expression in an advanced stage of CRC. This may suggest its possible involvement in colorectal tumorigenesis and invasion.

scholarly journals Expression of p53, bcl-2, and ki-67 Proteins in the Inflammatory Regenerative and Dysplastic Epithelial Lesions of Flat Colonic Mucosa

2008 ◽  
Vol 6 (1) ◽  
pp. 39-45 ◽  
Author(s):  
Svjetlana Radović ◽  
Zora Vukobrat-Bijedić ◽  
Ivan Selak ◽  
Mirsad Babić
Keyword(s):  
Cellular Proliferation ◽  
P53 Protein ◽  
Normal Mucosa ◽  
Labelling Index ◽  
Epithelial Dysplasia ◽  
Severe Dysplasia ◽  
Ki 67 ◽  
Mild Dysplasia ◽  
Sporadic Cases ◽  
Epithelial Lesions

The aim of the study was to define the distribution of p53, bcl-2 and Ki-67 proteins in the inflammatory-regenerative and dysplastic lesionsof the colon mucosa. The relationship between the presentation of p53, bcl-2 and Ki-67 proteins and the intensity of the inflammatory-regenerative and dysplastic lesions in the colon flat mucosa was investigated as well. Biopsy specimens from 270 patients were examined: 74 were classified as inflammatory-regenerative and 196 as dysplastic lesions (108 mild, 58 moderate, and 30 severe dysplasia). The expression of all three proteins was assessed on the basis of location, quantity, and intensity of immunostaining, by counting antigen positive cells, in comparison with normal mucosa and adenocarcinoma. p53 protein appears only in sporadic cases (6.6%) of severe dysplasia. Bcl-2 expression appears significantly (p<0.005) more often in cases of mild dysplasia (61.1%) compared to inflammatory-regenerative mucosa (14.8%). In cases of mild dysplasia, bcl-2 positive cells were spreading from the lower third to the middle third of the crypts. Bcl-2 expression was maintained through the stadiums of moderate and severe dysplasia (75.8%), where antigen positive cells were found all along the crypts. A significant increase (p<0.005) in the expression of nuclear protein Ki-67 was noticed in the stadiums of moderate (labelling index =26.3) compared to mild dysplasia (labelling index=16.7), and severe (labelling index=36.7) compared to moderate dysplasia, where the zone of cellular proliferation was widen along the whole crypt length. In the process of the development of epithelial dysplasia in the flat mucosa of colon a degree of the gene p53 alteration is low and appears only in sporadic cases of severe dysplasia. Mutation of the bcl-2 gene is involved in the genesis of the lesion but not in its progression to carcinoma. Increased expressionof Ki-67 protein speaks in favour of an increased cellular proliferation which, together with the above mentioned mechanisms, is involved in the process of occurrence and progression of epithelial dysplasia in the flat mucosa of colon.

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.

scholarly journals Deep Learning Algorithm for the Confirmation of Mucosal Healing in Crohn’s Disease, Based on Confocal Laser Endomicroscopy Images

2021 ◽  
Vol 30 (1) ◽  
pp. 59-65
Author(s):  
Anca Loredana Udristoiu ◽  
Daniela Stefanescu ◽  
Gabriel Gruionu ◽  
Lucian Gheorghe Gruionu ◽  
Andreea Valentina Iacob ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Deep Learning ◽  
Crohn's Disease ◽  
Colonic Mucosa ◽  
Mucosal Healing ◽  
Machine Learning Algorithms ◽  
Confocal Laser Endomicroscopy ◽  
Confocal Laser ◽  
Normal Colonic Mucosa ◽  
Test Accuracy

Background and Aims: Mucosal healing (MH) is associated with a stable course of Crohn’s disease (CD) which can be assessed by confocal laser endomicroscopy (CLE). To minimize the operator’s errors and automate assessment of CLE images, we used a deep learning (DL) model for image analysis. We hypothesized that DL combined with convolutional neural networks (CNNs) and long short-term memory (LSTM) can distinguish between normal and inflamed colonic mucosa from CLE images. Methods: The study included 54 patients, 32 with known active CD, and 22 control patients (18 CD patients with MH and four normal mucosa patients with no history of inflammatory bowel diseases). We designed and trained a deep convolutional neural network to detect active CD using 6,205 endomicroscopy images classified as active CD inflammation (3,672 images) and control mucosal healing or no inflammation (2,533 images). CLE imaging was performed on four colorectal areas and the terminal ileum. Gold standard was represented by the histopathological evaluation. The dataset was randomly split in two distinct training and testing datasets: 80% data from each patient were used for training and the remaining 20% for testing. The training dataset consists of 2,892 images with inflammation and 2,189 control images. The testing dataset consists of 780 images with inflammation and 344 control images of the colon. We used a CNN-LSTM model with four convolution layers and one LSTM layer for automatic detection of MH and CD diagnosis from CLE images. Results: CLE investigation reveals normal colonic mucosa with round crypts and inflamed mucosa with irregular crypts and tortuous and dilated blood vessels. Our method obtained a 95.3% test accuracy with a specificity of 92.78% and a sensitivity of 94.6%, with an area under each receiver operating characteristic curves of 0.98. Conclusions: Using machine learning algorithms on CLE images can successfully differentiate between inflammation and normal ileocolonic mucosa and can be used as a computer aided diagnosis for CD. Future clinical studies with a larger patient spectrum will validate our results and improve the CNN-SSTM model.

scholarly journals Immunohistochemical expression of MMP-2 in an experimental progression model of oral cancer

2014 ◽  
Vol 4 (2) ◽  
pp. 3-8
Author(s):  
B Shrestha ◽  
S Subedi ◽  
D Bayracharya ◽  
R Radhakrisnan
Keyword(s):  
Oral Cancer ◽  
Stromal Cells ◽  
Normal Mucosa ◽  
Matrix Metalloproteinase 2 ◽  
Early Event ◽  
Severe Dysplasia ◽  
Basal Cells ◽  
Oral Epithelial Dysplasia ◽  
Normal Oral Mucosa ◽  
Progression Model

The progression from normal to dysplasia to carcinoma involves series of molecular events. Matrix metalloproteinase-2 (MMP-2), proteolytic enzyme causes the degradation of the basement membrane, which is a primary step in cancer invasion and progression. The aim of this study was to compare the expression of MMP-2 in normal mucosa (NOM), oral epithelial dysplasia (OED) and Oral Squamous cell Carcinoma (OSCC).MMP-2 expression was evaluated immunohistochemically in NOM (n = 10), OED in each of its histological grades (n = 26) and OSCC of the lining mucosa (n = 19). A semi quantita­tive retrospective analysis was carried out in 100 cells in each of 5 different fields at 40x magnification in each case and the proportion of cells expressing MMP-2 were estimated. Suitable positive and negative controls were used for all our analysis. Expression scores of basal cells as well as adjacent stromal cells of OED and tumor cells as well as adjacent stromal cells of OSCC were analyzed. Expression of MMP-2 increased from NOM to OED through different grades to OSCC. Mann Whitney U test for comparison of expression for MMP-2 was statistically significant. However, the comparison for the ex­pression of MMP-2 in mild and moderate dysplasia (p=0.018) as well as moderate and severe dysplasia (p=0.026) was not statistically significant. Increase in the expression of MMP-2 from normal oral mucosa to dysplasia to oral cancer suggests it as an early event in oral carcinogenesis. DOI: http://dx.doi.org/10.3126/jcmc.v4i2.10852 Journal of Chitwan Medical College 2014; 4(2): 3-8

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