scholarly journals Quantitative Image Analysis of Epithelial and Stromal Area in Histological Sections of Colorectal Cancer: An Emerging Diagnostic Tool

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
R. Rogojanu ◽  
T. Thalhammer ◽  
U. Thiem ◽  
A. Heindl ◽  
I. Mesteri ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Normal Mucosa ◽  
Image Method ◽  
Cancer Tissue ◽  
The Novel ◽  
Adjacent Mucosa ◽  
Quantitative Measurements ◽  
Tumor Center ◽  
Quantitative Image ◽  
Tissue Compartments

In colorectal cancer (CRC), an increase in the stromal (S) area with the reduction of the epithelial (E) parts has been suggested as an indication of tumor progression. Therefore, an automated image method capable of discriminating E and S areas would allow an improved diagnosis. Immunofluorescence staining was performed on paraffin-embedded sections from colorectal tumors (16 samples from patients with liver metastasis and 18 without). Noncancerous tumor adjacent mucosa (n=5) and normal mucosa (n=4) were taken as controls. Epithelial cells were identified by an anti-keratin 8 (K8) antibody. Large tissue areas (5–63 mm2/slide) including tumor center, tumor front, and adjacent mucosa were scanned using an automated microscopy system (TissueFAXS). With our newly developed algorithms, we showed that there is more K8-immunoreactive E in the tumor center than in tumor adjacent and normal mucosa. Comparing patients with and without metastasis, the E/S ratio decreased by 20% in the tumor center and by 40% at tumor front in metastatic samples. The reduction of E might be due to a more aggressive phenotype in metastasis patients. The novel software allowed a detailed morphometric analysis of cancer tissue compartments as tools for objective quantitative measurements, reduced analysis time, and increased reproducibility of the data.

scholarly journals Downregulation of PAICS due to loss of chromosome 4q is associated with poor survival in stage III colorectal cancer

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0247169
Author(s):  
Yusuke Kobayashi ◽  
Kensuke Kumamoto ◽  
Hirokazu Okayama ◽  
Takuro Matsumoto ◽  
Hiroshi Nakano ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Progression ◽  
De Novo ◽  
Prognostic Significance ◽  
Normal Mucosa ◽  
Stage Iii ◽  
Copy Number Loss ◽  
Prognostic Impact ◽  
Cancer Specific Survival ◽  
Adjacent Mucosa

Phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS) encodes an enzyme that catalyzes de novo purine biosynthesis. Although PAICS has been implicated as a potential therapeutic target in several cancers, its clinical and prognostic significance in colorectal cancer (CRC) is not fully understood. To elucidate the roles of PAICS in CRC, we investigated PAICS expression in four cohorts consisting of a total of 1659 samples based on quantitative RT-PCR, microarray and RNA-seq analysis. Despite upregulated PAICS levels in tumor compared to those of normal mucosa, we found a decreasing trend of PAICS expression during tumor progression and metastasis. We conducted immunohistochemistry on 252 specimens, showing that PAICS protein was strongly expressed in the majority of CRCs, but not in adjacent mucosa. Notably, 29.0% of tumors lacked PAICS staining, and PAICS-negative expression in tumor had significant prognostic impact on poor cancer-specific survival in stage III CRC. Correspondingly, decreased levels of PAICS transcript were also correlated with poor relapse-free survival particularly in stage III patients, and this finding was robustly confirmed in three microarray datasets of a total of 802 stage II-III patients. Bioinformatics analysis of CRC tissues and cell lines consistently indicated a correlation between decreased PAICS expression and copy number loss of chromosome arm 4q. In conclusion, our results suggest that PAICS expression is downregulated during tumor progression due to genetic deletion of chromosome 4q in microsatellite stable but chromosomally unstable tumors. Furthermore, decreased expression of PAICS transcript or loss of PAICS protein may provide prognostic stratification for postoperative patients with stage III CRC.

Differential Expression of Mimecan and Thioredoxin Domain–Containing Protein 5 in Colorectal Adenoma and Cancer: A Proteomic Study

2007 ◽  
Vol 232 (9) ◽  
pp. 1152-1159 ◽  
Author(s):  
Yinghong Wang ◽  
Yu Ma ◽  
Bingjian Lü ◽  
Enping Xu ◽  
Qiong Huang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colorectal Adenoma ◽  
Normal Mucosa ◽  
Colorectal Adenomas ◽  
Differentially Expressed ◽  
Cancer Tissue ◽  
Differentially Expressed Proteins ◽  
Two Dimensional Gel Electrophoresis ◽  
Proteomic Study ◽  
Cancer Tissues

Adenoma is the major precursor lesion of colorectal cancer, one of the most common cancers worldwide. The elucidation of the molecular mechanism underlying adenoma is essential for early detection, prevention, and intervention of colorectal cancer. Using a combination of two-dimensional gel electrophoresis and mass spectrometry, we identified 27 differentially expressed proteins in adenoma, compared with matched normal mucosa and cancer tissue. Seventeen proteins were upregulated and six downregulated in adenoma when compared with the same proteins in individual-matched normal mucosa. Four were downregulated, but none upregulated in adenoma when compared with the same proteins in matched cancer tissue. Two novel proteins, mimecan and thioredoxin domain–containing protein 5 (TXNDC5), were further validated by Western blot in 8 colorectal adenomas and 19 cancers that were matched with normal mucosa. All adenoma and cancer tissues did not express mimecan, but all normal mucosa did ( P < 0.01). In contrast, TXNDC5 was significantly upregulated in colorectal adenoma and cancer tissues as compared with that in normal mucosa ( P < 0.05). This study clearly demonstrated that absence of mimecan and upregulation of TXNDC5 are involved in the early development of colorectal cancer. Thus, the differentially expressed proteins might serve as potential biomarkers for colorectal cancer detection and intervention.

scholarly journals Dickkopf-3 As a New Potential Marker for Neoangiogenesis in Colorectal Cancer: Expression in Cancer Tissue and Adjacent Non-Cancerous Tissue

2008 ◽  
Vol 24 (2) ◽  
pp. 101-109 ◽  
Author(s):  
Matthias Zitt ◽  
Gerold Untergasser ◽  
Albert Amberger ◽  
Patrizia Moser ◽  
Sylvia Stadlmann ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tissue Microarrays ◽  
Normal Mucosa ◽  
Cancer Tissue ◽  
Novel Therapies ◽  
Microvessel Count ◽  
Target Structure ◽  
Potential Marker ◽  
Tumor Endothelium ◽  
First Time

Gene expression of Dickkopf-3 (Dkk-3) has been shown to be upregulated in tumor endothelium of colorectal cancer (CRC). For the first time, we analyzed Dkk-3 protein expression in CRC and its potential as a marker for neoangiogenesis. We used tissue microarrays (TMAs) to investigate Dkk-3 in microvessels of 403 CRC samples, 318 appropriate adjacent non-cancerous samples and 127 normal colorectal samples. Of cancer samples with CD31-positive microvessels, 67.7% were positive for Dkk-3. Dkk-3 staining was demonstrated in endothelial cells of all microvessels in nearly all cases. Dkk-3-positive samples showed a higher mean microvessel count than did Dkk-3-negative samples (P=0.001). Dkk-3 expression increased with rising numbers of microvessels per sample (P<0.0001). In adjacent samples with CD31-positive microvessels, 56% were Dkk-3-positive in all microvessels. Similar to cancer samples, Dkk-3-positive adjacent samples had a higher mean microvessel count than did Dkk-3-negative samples (P<0.0001), and Dkk-3 expression also increased with rising numbers of microvessels (P<0.0001). All microvessels in normal mucosa samples were negative for Dkk-3.Dkk-3 can be considered a putative pro-angiogenic protein in neovascularization and may possibly be a marker for neoangiogenesis in CRC. Further investigations will elucidate whether Dkk-3 is a target structure for novel therapies.

scholarly journals Rearrangements of Blood and Tissue Fatty Acid Profile in Colorectal Cancer - Molecular Mechanism and Diagnostic Potential

2021 ◽  
Vol 11 ◽  
Author(s):  
Adriana Mika ◽  
Katarzyna Duzowska ◽  
Lukasz P. Halinski ◽  
Alicja Pakiet ◽  
Aleksandra Czumaj ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fatty Acid ◽  
Healthy Subjects ◽  
Roc Analysis ◽  
Normal Mucosa ◽  
Cancer Tissue ◽  
Normal Colon Mucosa ◽  
Non Invasive ◽  
Diagnostic Potential ◽  
Ht 29

Colorectal cancer (CRC) is often diagnosed at an advanced stage due to the invasiveness of colonoscopy; thus, non-invasive CRC diagnostics are desirable. CRC is associated with lipid alterations. We aimed to verify whether fatty acid (FA) profiles in CRC patients may serve as a potential diagnostic tool for CRC diagnosis. FA profiles were assayed by GC-MS in cancer tissue, paired normal mucosa and serum from CRC patients and healthy controls. The levels of very long FAs – VLCFAs (26:0, 28:0 and 26:1) were the most highly increased FAs in cancer tissue compared to normal colon mucosa. Moreover, these FA were present in serum of CRC patients, they were absent in the serum of healthy subjects, or present in only trace amounts. To verify if cancer cells are the source of small amounts of these VLCFAs in the serum of patients we performed experiment in HT-29 CRC cells, which proved that CRC cells can produce and release VLCFAs into the blood. Most importantly, we defined a panel of FAs that may be assayed in a single analysis that definitely distinguishes CRC patients and healthy subjects, which was confirmed by PLS-DA and multivariate ROC analysis (AUC = 0.985). This study shows that selected FA panel may serve as a diagnostic marker for CRC.

196 A Sensitive Methylation Marker Panel That Discriminates Normal Mucosa from Colorectal Cancer Tissue with High Specificity

2009 ◽  
Vol 136 (5) ◽  
pp. A-36
Author(s):  
Patric Urfer ◽  
Stefan Weis ◽  
Faiza Noreen ◽  
Mirco Menigatti ◽  
Corina Kim-Fuchs ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Specificity ◽  
Normal Mucosa ◽  
Cancer Tissue ◽  
Marker Panel ◽  
Colorectal Cancer Tissue ◽  
Methylation Marker

Prospective study on prognostic significance of DNA ploidy and Ki-67 expression in colorectal cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21184-21184
Author(s):  
C. Saggia ◽  
A. Santagostino ◽  
G. Forti ◽  
G. Biaggi ◽  
G. Angeli ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Proliferative Activity ◽  
Dna Ploidy ◽  
Prognostic Significance ◽  
Normal Mucosa ◽  
Disease Stage ◽  
Cancer Tissue ◽  
Ki 67 ◽  
Number Of Patients ◽  
Immuno Histochemistry

21184 Background: The prognostic value of flow cytometry DNA ploidy and Ki-67 expression in colorectal carcinomas has not been defined yet. The study tries to correlate tumoral DNA ploidy and proliferative activity (Ki-67) with therapy response, Overall Survival (OS), Disesase Specific Survival (DSS) and Disease Free Survival (DFS). Methods: From 01/09/02 to 30/06/05, 3 samples of cancer tissue and 1 sample of normal mucosa has been collected from all operating pieces of colorectal cancer. These samples were frosen and later disgregated, treated and coloured with Propidium Iodide. DNA ploidy was evaluated by FACSCalibur cytofluorimetry. Normal mucosa tissue was our internal control. Ki-67 was evaluated by immuno-histochemistry in all tumoral samples. All the patients were cured with chemo- and/or radiotherapy in our divisions. Results: 67 patients (M/F 35/32); median age was 70; staging: 19% I, 33% II, 30% III, 18% IV. We found aneuploidy in 65,7% of carcinoma and Ki-67 median expression was 55%. DNA tumoral heterogeneity was present in 27% of patients. DNA aneuploidy correlates with advanced disease stage at diagnosis (p<0,01), with high number of metastatic lymphnodes (p<0,005) and with serological markers positivity (p<0,04). After surgery and chemotherapy 35% of the patients with aneuploid carcinoma and high proliferative activity (Ki-67>55%) do not show evident disease versus 100% of patients with DNA diploidy and lower Ki-67. Tumoral aneuploidy correlates in a significative way with lower OS (48% vs 89% of diploid patients), lower DSS (tumor death happened just in patients with aneuploid DNA in every disease stages), with lower DFS (18% vs 86% of diploid patients). Univariated analysis stated that aneuploidy determinates an Odd Ratio=5,7 to develop disease progression (p=0,033). At the moment Ki-67 expression with 55% cut-off does not seem to correlate with OS, DSS and DFS. Conclusions: Preliminar results (the study is still in progress) seem to suggest that cytofluorimetric DNA-ploidy has a prognostic and predictive significance in colo-rectal carcinomas. Ki-67 expression (immuno-histochemistry) has an uncertain significance. The small number of patients and the short follow-up do not allow us to reach any definitive conclusions, but the study is worth to go on. No significant financial relationships to disclose.

Distribution of neuroendocrine marker-positive cells in colorectal cancer tissue and adjacent mucosa.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 617-617
Author(s):  
Takashi Ogimi ◽  
Sotaro Sadahiro ◽  
Hiroshi Miyakita ◽  
Gota Saito ◽  
Lin Fung Chan ◽  
...  
Keyword(s):  
Chromogranin A ◽  
Normal Mucosa ◽  
Tumor Location ◽  
Left Colon ◽  
Cancer Tissue ◽  
Positive Staining ◽  
Right Colon ◽  
Neuroendocrine Marker ◽  
Adjacent Mucosa ◽  
The Right

617 Background: Neuroendocrine carcinoma (NEC) is a rare disease and has been reported to most frequently arise in the right side of the colon. In the 2010 WHO classification, mixed adenoneuroendocrine carcinoma (MANEC) was defined as a neoplasm consisting of NEC and adenocarcinoma components. To clarify the histogenesis of NEC, we attempted to detect neuroendocrine marker-positive cells in cancer tissue and in the adjacent mucosa in patients with adenocarcinoma. Methods: The study group comprised 390 patients with Stage II or III colorectal adenocarcinoma between 2007 and 2012. Immunostaining was performed with anti chromogranin A, synaptophysin, and CD56 antibodies. Cases with positively stained cells in cancer tissue were defined as positive. In the adjacent mucosa, at least 5 cm from the tumor, the numbers of positive cells per 15 HPF were measured. Results: Tumor location was right side in 181 patients, left side in 173, and the rectum in 36 patients. Positive rates of Chromogranin A in cancer tissues were 23.7% in the right colon, 13.2% in the left colon, and 19.4% in the rectum. Those of synaptopysin were 35.3%, 21.9%, and 30.6%, respectively. Those of CD56 were 22.6%, 8.0%, and 16.7%, respectively. Positive rates of these three markers in right colon were significantly higher than those in left colon and rectum. (p = 0.0115, p = 0.0054, p = 0.0062). In the adjacent mucosa, the mean numbers of positive cells for chromogranin A were 62.2 ± 20.5 in the right colon, 131.9 ± 44.7 in the left colon, and 243.7 ± 60.2 in the rectum (p < 0.001). Those for synaptophysin were 47.7 ± 23.5, 95.3 ± 35.1, and 156.9 ± 56.8, respectively. (p < 0.001). There were no significant differences in the number of positive cells for CD56 among the sites (p = 0.295). Conclusions: In cancer tissue, the rate of positive staining for neuroendocrine marker-positive cells was higher in the right side of the colon, whereas in normal mucosa the rates of positive staining for these cells were higher in the sigmoid colon and the rectum. These results suggest that neuroendocrine marker-positive cells are an acquired characteristic of cancer tissue.

Metabolomics investigation of human colorectal cancer tissue, adjacent mucosa, and stool collected from CRC patients.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. e14688-e14688
Author(s):  
Dustin George Brown ◽  
Elizabeth Ryan ◽  
Erica Borresen ◽  
Joanne O'Malia ◽  
Sangeeta Rao
Keyword(s):  
Colorectal Cancer ◽  
Cancer Tissue ◽  
Human Colorectal Cancer ◽  
Colorectal Cancer Tissue ◽  
Adjacent Mucosa

Melanoma-Associated Antigen (MAGE) Expression in the Normal Mucosa around Colorectal Cancer after Curative Resection: Presence of Undetectable Free Cancer Cells?

2011 ◽  
Vol 26 (2) ◽  
pp. 88-93 ◽  
Author(s):  
Chang-Ho Jeon ◽  
Dae-Dong Kim ◽  
Han-Il Lee ◽  
Hoon-Kyu Oh ◽  
Hyun-Dong Chae
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Curative Resection ◽  
Normal Mucosa ◽  
Clinical Findings ◽  
Cancer Tissue ◽  
Benign Diseases ◽  
Mucosal Tissues ◽  
Mucosal Site ◽  
Colorectal Diseases

Purpose Curative surgical resection is of great importance and some trials have been performed to identify free undetectable cancer cells using molecular markers. The aim of this study is to investigate melanoma-associated antigen (MAGE) expression in normal mucosa around colorectal cancer and its clinical significance. Material and method From October 2003 to June 2004, we collected 46 colorectal cancer and matched normal mucosal tissues within 20 mm, 20 to 50 mm and more than 50 mm from tumors after the curative operation. Twenty-two mucosal tissues were harvested from patients with benign colorectal diseases as controls. MAGE expression was assayed using nested RT-PCR of MAGE A1-6 mRNA. Results The MAGE expression rates in cancer tissue and adjacent normal mucosa were 65.2%, 6.5% (<20 mm), 2.2% (20–50 mm) and 0.0% (>50 mm), respectively, while MAGE was not expressed in the mucosa of benign diseases. The MAGE-positive cases in the normal mucosa around tumors were located in the left colon or rectum, and one patient showed anastomotic mucosal site recurrence. Conclusions MAGE expression in normal-appearing mucosa around colorectal cancer showed some clinical findings suggesting the presence of undetectable free cancer cells after curative resection.

Sign in / Sign up

Export Citation Format

Share Document