scholarly journals Discordance between immunochemistry of mismatch repair proteins and molecular testing of microsatellite instability in colorectal cancer

ESMO Open ◽  
2021 ◽  
Vol 6 (3) ◽  
pp. 100120
Author(s):  
A. Guyot D'Asnières De Salins ◽  
G. Tachon ◽  
R. Cohen ◽  
L. Karayan-Tapon ◽  
A. Junca ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Molecular Testing ◽  
Mismatch Repair Proteins

Use of immunohistochemical versus microsatellite analyses as markers for colorectal cancer

2017 ◽  
Vol 43 (2) ◽  
pp. 134-141
Author(s):  
Utku Tantoğlu ◽  
Seher Yüksel ◽  
Cihangir Akyol ◽  
Haldun Doğan ◽  
Nükhet Kutlay ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Immunohistochemical Analysis ◽  
Sporadic Colorectal Cancer ◽  
Molecular Tests ◽  
Antibody Panel ◽  
Mismatch Repair Proteins ◽  
Good Concordance

Abstract Objectives: Our aim was to determine how well immunohistochemical analysis identified colon cancer patients with microsatellite instability in Turkish patients. Material and methods: Subjects were patients that underwent surgery for colorectal cancer in our institution between 2006 and 2011. Patients were grouped as: (1) suspected Lynch syndrome (n=14), (2) familial colorectal cancer (n=14), and (3) sporadic colorectal cancer groups (n=14). Mismatch repair proteins were analyzed by a four antibody-panel immunohistochemistry. Microsatellite instability analysis was conducted on DNA samples using MSI-PCR followed by fragment analysis. Results: The immunohistochemistry and PCR results had good concordance in 35/42 patients. Both microsatellite instability and at least one mismatch repair protein deficiency were detected in 11 patients, and both microsatellite stability and normal expression of mismatch repair proteins were detected in 24 patients. Test results were discordant in seven of the patients. Conclusion: As it is not feasible to perform expensive molecular tests in healthcare units in many developing countries, the four antibody-panel immunohistochemistry is a reliable and affordable method for screening for colorectal cancer, including Lynch syndrome and sporadic cases when suspected.

scholarly journals Mismatch Repair Proteins and Microsatellite Instability in Colorectal Carcinoma (MLH1, MSH2, MSH6 and PMS2): Histopathological and Immunohistochemical Study

2017 ◽  
Vol 5 (1) ◽  
pp. 9-13 ◽  
Author(s):  
Nour El Hoda S. Ismael ◽  
Samar A. El Sheikh ◽  
Suzan M. Talaat ◽  
Eman M. Salem
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Immunohistochemical Study ◽  
Survival Rates ◽  
Immunohistochemical Expression ◽  
Egyptian Patients ◽  
Mismatch Repair Proteins ◽  
Microsatellite Stability ◽  
Colorectal Cancer Patients

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers worldwide. Microsatellite instability (MSI) is detected in about 15% of all colorectal cancers. CRC with MSI has particular characteristics such as improved survival rates and better prognosis. They also have a distinct sensitivity to the action of chemotherapy.AIM: The aim of the study was to detect microsatellite instability in a cohort of colorectal cancer Egyptian patients using the immunohistochemical expression of mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2).MATERIAL AND METHODS: Cases were divided into Microsatellite stable (MSS), Microsatellite unstable low (MSI-L) and Microsatellite unstable high (MSI-H). This Microsatellite stability status was correlated with different clinicopathological parameters.RESULTS: There was a statistically significant correlation between the age of cases, tumor site & grade and the microsatellite stability status. There was no statistically significant correlation between the gender of patients, tumor subtype, stage, mucoid change, necrosis, tumor borders, lymphocytic response, lymphovascular emboli and the microsatellite stability status.CONCLUSION: Testing for MSI should be done for all colorectal cancer patients, especially those younger than 50 years old, right sided and high-grade CRCs.

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.

scholarly journals Beyond Microsatellite Instability: Evolving Strategies Integrating Immunotherapy for Microsatellite Stable Colorectal Cancer

2021 ◽  
Vol 22 (8) ◽  
Author(s):  
Federica Pecci ◽  
Luca Cantini ◽  
Alessandro Bittoni ◽  
Edoardo Lenci ◽  
Alessio Lupi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Cancer Progression ◽  
Checkpoint Inhibitors ◽  
Tnm Classification ◽  
Standard Of Care ◽  
First Line Therapy ◽  
Combination Strategies ◽  
The Impact

Opinion statementAdvanced colorectal cancer (CRC) is a heterogeneous disease, characterized by several subtypes with distinctive genetic and epigenetic patterns. During the last years, immune checkpoint inhibitors (ICIs) have revamped the standard of care of several tumors such as non-small cell lung cancer and melanoma, highlighting the role of immune cells in tumor microenvironment (TME) and their impact on cancer progression and treatment efficacy. An “immunoscore,” based on the percentage of two lymphocyte populations both at tumor core and invasive margin, has been shown to improve prediction of treatment outcome when added to UICC-TNM classification. To date, pembrolizumab, an anti-programmed death protein 1 (PD1) inhibitor, has gained approval as first-line therapy for mismatch-repair-deficient (dMMR) and microsatellite instability-high (MSI-H) advanced CRC. On the other hand, no reports of efficacy have been presented in mismatch-repair-proficient (pMMR) and microsatellite instability-low (MSI-L) or microsatellite stable (MSS) CRC. This group includes roughly 95% of all advanced CRC, and standard chemotherapy, in addition to anti-EGFR or anti-angiogenesis drugs, still represents first treatment choice. Hopefully, deeper understanding of CRC immune landscape and of the impact of specific genetic and epigenetic alterations on tumor immunogenicity might lead to the development of new drug combination strategies to overcome ICIs resistance in pMMR CRC, thus paving the way for immunotherapy even in this subgroup.

scholarly journals Immunotherapy, Inflammation and Colorectal Cancer

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 618 ◽  
Author(s):  
Charles Robert Lichtenstern ◽  
Rachael Katie Ngu ◽  
Shabnam Shalapour ◽  
Michael Karin
Keyword(s):  
Colorectal Cancer ◽  
Growth Factor ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
The United States ◽  
Chemotherapeutic Agents ◽  
Adoptive T Cell Therapy ◽  
Current Status ◽  
Cancer Type ◽  
T Cell Therapy

Colorectal cancer (CRC) is the third most common cancer type, and third highest in mortality rates among cancer-related deaths in the United States. Originating from intestinal epithelial cells in the colon and rectum, that are impacted by numerous factors including genetics, environment and chronic, lingering inflammation, CRC can be a problematic malignancy to treat when detected at advanced stages. Chemotherapeutic agents serve as the historical first line of defense in the treatment of metastatic CRC. In recent years, however, combinational treatment with targeted therapies, such as vascular endothelial growth factor, or epidermal growth factor receptor inhibitors, has proven to be quite effective in patients with specific CRC subtypes. While scientific and clinical advances have uncovered promising new treatment options, the five-year survival rate for metastatic CRC is still low at about 14%. Current research into the efficacy of immunotherapy, particularly immune checkpoint inhibitor therapy (ICI) in mismatch repair deficient and microsatellite instability high (dMMR–MSI-H) CRC tumors have shown promising results, but its use in other CRC subtypes has been either unsuccessful, or not extensively explored. This Review will focus on the current status of immunotherapies, including ICI, vaccination and adoptive T cell therapy (ATC) in the treatment of CRC and its potential use, not only in dMMR–MSI-H CRC, but also in mismatch repair proficient and microsatellite instability low (pMMR-MSI-L).

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