scholarly journals Histomorphology and Molecular Genetics in Different Intra-Tumoral Zones and Matched Metastatic Lymph Nodes of Colorectal Cancer with Heterogenous Mismatch Repair Status

2021 ◽  
Author(s):  
Jing Zhang ◽  
Xin Zhang ◽  
Qian Wang ◽  
Yuyin Xu ◽  
Qianlan Yao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Protein Expression ◽  
Lymph Nodes ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Promoter Methylation ◽  
Gene Mutations ◽  
Metastatic Lymph Nodes ◽  
Molecular Alterations ◽  
Metastatic Lymph

Abstract Objective: To better understand the clinicopathological characteristics and molecular alterations in different intra-tumoral components of colorectal cancer (CRC) with heterogeneity of mismatch repair (MMR) protein expression and microsatellite instability (MSI) status.Methods: We identified 4 cases of CRC with heterogenous MMR protein expression and analyzed the histopathological features, MSI status and other molecular alterations in separately microdissected intra-tumoral zones and lymph node metastases by polymerase chain reaction (PCR) -based MSI testing, MLH1 promoter methylation and targeted next-generation sequencing (NGS).Results: Microsatellite instability-high (MSI-H) was identified in the MLH1/PMS2 deficient zones in Case 1-3, and in the MSH2/MSH6 deficient zone in Case 4, while MSS was in all the intra-tumoral zones and metastatic lymph nodes with proficient MMR (pMMR). Furthermore, heterogeneity of MLH1 promoter methylation and/or other common driving gene mutations of CRC, such as KRAS, PIK3CA and so on, was identified in all the 4 CRCs. In addition, 75% (3/4) of cases showed heterogeneity of histomorphology in intra-tumoral components and metastatic lymph nodes (Case 1, 2, 4), and all the corresponding metastatic lymph nodes were moderate differentiation with MSS/pMMR (Case 2, 3). Conclusions: The heterogeneous MSI status is highly correlated with histomorphological heterogeneity, which is also an important clue for the heterogeneity of drive gene mutations in CRC. These results suggest that it is essential to detect MMR protein expression and other gene mutations in metastases before treatment, especially for the CRCs with heterogenous MMR protein expression or histomorphology.

Loss of ASXL1 protein is associated with lymph node metastasis in colorectal cancer

2019 ◽  
Author(s):  
Jun Ho Lee ◽  
Ju-Hee Lee ◽  
Byung Kyu Ahn ◽  
Seung Sam Paik ◽  
Hyunsung Kim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Protein Expression ◽  
Lymph Nodes ◽  
Disease Free Survival ◽  
Prognostic Impact ◽  
Metastatic Lymph Nodes ◽  
Node Metastasis ◽  
Metastatic Lymph

Abstract Background The function of ASXL1 protein in colorectal cancer has not been investigated yet. The purpose of this study was to investigate the clinicopathological and prognostic impact of ASXL1 protein expression on colorectal cancer.Methods We performed immunohistochemical staining of ASXL1 protein using tissue microarrays of 408 colorectal cancers, 46 normal colonic mucosae, 48 adenomas, and 92 metastatic lymph nodes. The intensity of expression was scored as 0–3, and the extent of staining was scored as 0–4, based on the percentage of positive cells. The immunoreactivity score (IRS) was calculated by multiplying the two scores.Results ASXL1 protein expression rates were 89.1% in normal mucosae, 72.9% in tubular adenomas, 44.4% in adenocarcinomas, and 28.3% in metastatic lymph nodes ( p < 0.001). With respect to the IRS cut-off score, the mean tumor size was smaller in the IRS 0–6 group than in the IRS 8–12 group (4.9 ± 2.1 vs. 6.3 ± 2.7 cm, p = 0.002). Lymph node metastasis was more frequent in the IRS 0–6 group than in the IRS 8–12 group (56.3% vs. 33.3%, p = 0.034). Lymphatic invasion was more frequent in the 0–6 group than in the IRS 8–12 group (56.0% vs. 33.3%, p = 0.035). The 5-year disease-free survival rate did not differ between two groups at stage II and stage III.Conclusions ASXL1 protein might act as a tumor suppressor in colorectal cancer. The loss of ASXL1 expression might be associated with metastasis via the lymphatic system to the lymph nodes.

High Expression of sLex Associated with Poor Survival in Argentinian Colorectal Cancer Patients

2014 ◽  
Vol 29 (1) ◽  
pp. e30-e39 ◽  
Author(s):  
Ariel Zwenger ◽  
Martin Rabassa ◽  
Sandra Demichelis ◽  
Gabriel Grossman ◽  
Amada Segal-Eiras ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Nodes ◽  
Cancer Patients ◽  
Normal Mucosa ◽  
Poor Survival ◽  
Primary Tumors ◽  
Metastatic Lymph Nodes ◽  
Metastatic Lymph ◽  
Colorectal Cancer Patients

Aim Colorectal cancer (CRC) is one of the most prevalent malignancies in Argentina with 11,043 new cases and 6,596 deaths estimated to have occurred in 2008. The present study was developed to clarify the differential expression of MUC1, MUC2, sLex, and sLea in colorectal cancer patients and their relationship with survival and clinical and histological features. Methods Ninety primary tumor samples and 43 metastatic lymph nodes from CRC patients were studied; follow-up was documented. Twenty-six adenoma and 68 histological normal mucosa specimens were analyzed. An immunohistochemical approach was applied and statistical analysis was performed. Results In tumor samples, MUC1, sLea, and sLex were highly expressed (94%, 67%, and 91%, respectively); also, we found a significantly increased expression of the 3 antigens in primary tumors and metastatic lymph nodes compared with normal mucosa and adenomas. MUC2 was expressed in 52% of both normal mucosa and CRC samples; this reactivity significantly decreased in metastatic lymph nodes (p<0.05). A multiple comparison analysis showed that MUC1 and sLex discriminated among 3 groups: normal, adenoma, and CRC tissues. The increase of sLex expression showed an association with recurrence, and survival analysis showed that a high sLex staining was significantly associated with a poor survival. By multivariate analysis MUC1 inmunoreactivity correlated positively and significantly with tumor size, while MUC2 expression showed the opposite correlation. Conclusions The correlation of sLex overexpression in primary tumors and metastatic lymph nodes, the discrimination among the normal, adenoma, and CRC groups based on sLex expression, as well as its association with recurrence and survival, all suggest a prognostic role of sLex in Argentinian CRC patients.

scholarly journals Fibrosis in metastatic lymph nodes is clinically correlated to poor prognosis in colorectal cancer

Oncotarget ◽  
2018 ◽  
Vol 9 (51) ◽  
pp. 29574-29586 ◽  
Author(s):  
Daiji Ikuta ◽  
Toru Miyake ◽  
Tomoharu Shimizu ◽  
Hiromichi Sonoda ◽  
Ken-Ichi Mukaisho ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Nodes ◽  
Poor Prognosis ◽  
Metastatic Lymph Nodes ◽  
Metastatic Lymph

scholarly journals The number of metastatic lymph nodes exhibiting poorly differentiated clusters predicts survival in patients with pStage III colorectal cancer

2015 ◽  
Vol 31 (2) ◽  
pp. 283-290 ◽  
Author(s):  
Osamu Kinoshita ◽  
Mitsuo Kishimoto ◽  
Yasutoshi Murayama ◽  
Yoshiaki Kuriu ◽  
Masayoshi Nakanishi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Nodes ◽  
Metastatic Lymph Nodes ◽  
Metastatic Lymph ◽  
Poorly Differentiated Clusters ◽  
Poorly Differentiated

Double somatic mutations in mismatch repair genes are frequent in colorectal cancer after Hodgkin's lymphoma treatment

Gut ◽  
2016 ◽  
Vol 67 (3) ◽  
pp. 447-455 ◽  
Author(s):  
Lisanne S Rigter ◽  
Petur Snaebjornsson ◽  
Efraim H Rosenberg ◽  
Peggy N Atmodimedjo ◽  
Berthe M Aleman ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
General Population ◽  
Mismatch Repair ◽  
Promoter Methylation ◽  
Hodgkin’S Lymphoma ◽  
Gene Mutations ◽  
Hodgkin's Lymphoma ◽  
Molecular Characteristics ◽  
Increased Risk ◽  
General Population Cohort

ObjectiveHodgkin's lymphoma survivors who were treated with infradiaphragmatic radiotherapy or procarbazine-containing chemotherapy have a fivefold increased risk of developing colorectal cancer (CRC). This study aims to provide insight into the development of therapy-related CRC (t-CRC) by evaluating histopathological and molecular characteristics.Design54 t-CRCs diagnosed in a Hodgkin's lymphoma survivor cohort were analysed for mismatch repair (MMR) proteins by immunohistochemistry, microsatellite instability (MSI) and KRAS/BRAF mutations. MSI t-CRCs were evaluated for promoter methylation and mutations in MMR genes. Pathogenicity of MMR gene mutations was evaluated by in silico predictions and functional analyses. Frequencies were compared with a general population cohort of CRC (n=1111).ResultsKRAS and BRAF mutations were present in 41% and 15% t-CRCs, respectively. Compared with CRCs in the general population, t-CRCs had a higher MSI frequency (24% vs 11%, p=0.003) and more frequent loss of MSH2/MSH6 staining (13% vs 1%, p<0.001). Loss of MLH1/PMS2 staining and MLH1 promoter methylation were equally common in t-CRCs and the general population. In MSI CRCs without MLH1 promoter methylation, double somatic MMR gene mutations (or loss of heterozygosity as second hit) were detected in 7/10 (70%) t-CRCs and 8/36 (22%) CRCs in the general population (p=0.008). These MMR gene mutations in t-CRCs were classified as pathogenic. MSI t-CRC cases could not be ascribed to Lynch syndrome.ConclusionsWe have demonstrated a higher frequency of MSI among t-CRCs, which results from somatic MMR gene mutations. This suggests a novel association of somatic MMR gene mutations with prior anticancer treatment.

scholarly journals A prospective study of dual-energy CT in determining the metastatic and non-metastatic lymph nodes of colorectal cancer

2020 ◽  
Author(s):  
Lin Qiu ◽  
Junjiao Hu ◽  
Zeping Weng ◽  
Fasheng Li ◽  
Fei Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Nodes ◽  
Electron Density ◽  
Sensitivity And Specificity ◽  
Dual Energy ◽  
Dual Energy Ct ◽  
Metastatic Node ◽  
Metastatic Lymph Nodes ◽  
Quantitative Parameters ◽  
Metastatic Lymph

Abstract Background To explore the ability of Dual-energy CT (DECT) to differentiate metastatic from non-metastatic lymph nodes in colorectal cancer (CRC). Methods Seventy-one patients with primary CRC underwent contrast-enhanced DECT imaging before surgery. The colorectal specimen was scanned after surgery, and lymph nodes were matched to the pathology report. The DECT quantitative parameters were analyzed: dual-energy curve slope value(λHU), standardized iodine concentration (n△HU), iodine water ratio (nIWR), electron density value (nρeff), and effective atom-number (nZ), for the metastatic and non-metastatic lymph node differentiation. Also, sensitivity and specificity analyses were performed by using receiver operating characteristic curve. Results One hundred and fifty lymph nodes including 66 non-metastatic and 84 metastatic lymph nodes were matched using the radiological-pathological correlation. Metastatic node had a significantly greater λHU, n△HU and nIWR values than non-metastatic node in both arterial and venous phases (P < 0.01). The AUC, sensitivity and specificity were 0.80, 80.30% and 65.48% for λHU; 0.86, 69.70% and 95.24% for n△HU; 0.88, 71.21% and 95.24% for nIWR in the arterial phase. No significant difference was found in electron density and effective Z value for differentiation. Conclusion Dual-energy CT quantitative parameters may be helpful in diagnosing metastatic lymph nodes of CRC.

scholarly journals A Study of the Correlation Between M2 Macrophages and Lymph Node Metastasis of Colorectal Cancer

2020 ◽  
Author(s):  
Yanping Wang ◽  
Jikun Wang ◽  
Jinhao Liu ◽  
Zuoxiu Shi ◽  
Yanlei Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Lymph Nodes ◽  
Comprehensive Treatment ◽  
M2 Macrophage ◽  
M2 Macrophages ◽  
Metastatic Lymph Nodes ◽  
Node Metastasis ◽  
Metastatic Lymph

Abstract Background: Lymph node metastasis is a major prognostic factor of colorectal cancer and an important indicator for individualized treatment. M2 macrophages play a key role in carcinogenesis and tumor development, not only enhancing invasiveness, but also promoting lymph node metastasis. The purpose of this study was to investigate the effect of CD163-positive M2 macrophages on lymph node metastasis in colorectal cancer.Methods: Postoperative lymph node tissues were obtained from 120 patients with colorectal cancer who underwent radical surgery in the First Affiliated Hospital of Jinzhou Medical University between December 2019 and May 2020. We detected the expression of the CD163 protein in lymph nodes by immunohistochemistry. Furthermore, the relationship between M2 macrophages identified by this marker and lymph node metastasis were analyzed using the independent sample T-test and Chi-square test.Results: M2 macrophages were increased not only in metastatic lymph nodes, but also in non-metastatic lymph nodes adjacent to the cancer. The M2 macrophage count was higher in patients with macro-metastases than in those with micro-metastases.Conclusions: M2 macrophages represent an important factor for the promotion of lymph node metastasis in colorectal cancer, and may be a potential marker for its prediction. This may offer a new target for the comprehensive treatment of colorectal cancer.

scholarly journals Detection of Mismatch Repair and Microsatellite Instability in Colorectal Cancer Patients

2020 ◽  
Vol 18 (2) ◽  
Author(s):  
Muhammad Ishaque Faizee
Keyword(s):  
Colorectal Cancer ◽  
Protein Expression ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Poor Response ◽  
Protein Product ◽  
Mismatch Repair Proteins ◽  
Altered Gene ◽  
Colorectal Cancer Patients ◽  
Mmr Proteins

Introduction:  Colorectal cancer is the third most common cancer worldwide. Microsatellite instability (MSI) contributes to be one of the main mechanisms in colorectal cancer. Individuals with MSI tumors have loss of expression of one or more Mismatch Repair proteins. MSI tumors have better survival rate than microsatellite stable (MSS) tumors, poor response to 5FU-based adjuvant chemotherapy and relatively successful immunotherapy in metastatic MSI tumors. Immunohistochemistry recognizes altered gene by recognizing loss of its protein product. Based on the presence or absence of Mismatch repair proteins, groups are classified into Mismatch repair proficient (MMR-p) and Mismatch repair deficient (MMR-d).  Aim:  To investigate the immunohistochemical profile of Mismatch repair proteins namely: hMLH1, hMSH2, hMSH6, and hPMS2 in surgically resected colorectal cancer specimens.  Materials and Method:  A total of 76 cases were selected from the Histopathology Department of HTAA to determine MMR protein expression status. Cases were either MMR-p or MMR-d. Results:  Of the specimens which were properly immunostained, seventeen out of seventy-six cases (22.37%) showed loss of one or more MMR proteins expression and thus were MMR-d. MLH1, MSH2, MSH6 and PMS2 protein expression was detected as 85.53% (65/76), 81.6% (62/76), 88.16% (67/76), and 76.32% (58/76), respectively. Conclusion: Mismatch repair proteins profile should be done using immunohistochemistry in  local laboratories on these selected cases before referring for the expensive molecular test.

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