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

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.

Download Full-text

Detection of Mismatch Repair and Microsatellite Instability in Colorectal Cancer Patients

IIUM Medical Journal Malaysia ◽

10.31436/imjm.v18i2.627 ◽

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.

Download Full-text

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

ESMO Open ◽

10.1016/j.esmoop.2021.100120 ◽

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

Download Full-text

Correction to: Variation in Blood and Colorectal Epithelia’s Key Trace Elements along with Expression of Mismatch Repair Proteins from Localized and Metastatic Colorectal Cancer Patients

Biological Trace Element Research ◽

10.1007/s12011-019-01787-3 ◽

2019 ◽

Vol 194 (2) ◽

pp. 629-629

Author(s):

Ali Ghorbani Ranjbary ◽

Jalil Mehrzad ◽

Hesam Dehghani ◽

Abbas Abdollahi ◽

Saman Hosseinkhani

Keyword(s):

Colorectal Cancer ◽

Trace Elements ◽

Metastatic Colorectal Cancer ◽

Cancer Patients ◽

Mismatch Repair ◽

Mismatch Repair Proteins ◽

Colorectal Cancer Patients

Download Full-text

S1993 Comparison Between Routine Immunohistochemistry for Mismatch Repair Proteins Versus Revised Bethesda Guidelines in the Diagnosis of Lynch Syndrome in a Non-Selected Population of Colorectal Cancer Patients

Gastroenterology ◽

10.1016/s0016-5085(10)61364-9 ◽

2010 ◽

Vol 138 (5) ◽

pp. S-297

Author(s):

Lucía Pérez-Carbonell ◽

Clara Ruiz-Ponte ◽

Xavier Bessa ◽

José-Luis Soto ◽

Adela Castillejo ◽

...

Keyword(s):

Colorectal Cancer ◽

Lynch Syndrome ◽

Cancer Patients ◽

Mismatch Repair ◽

Bethesda Guidelines ◽

Mismatch Repair Proteins ◽

Revised Bethesda Guidelines ◽

Colorectal Cancer Patients

Download Full-text

Use of immunohistochemical versus microsatellite analyses as markers for colorectal cancer

Turkish Journal of Biochemistry ◽

10.1515/tjb-2017-0050 ◽

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.

Download Full-text

Mismatch Repair Proteins (MLH1, MSH2, MSH6, and PMS2) Immunohistochemical Expression and Microsatellite Instability in Endometrial Carcinoma

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2020.4300 ◽

2020 ◽

Vol 8 (A) ◽

pp. 306-310

Author(s):

Nour El Hoda S. Ismael ◽

Hala M. Naguib ◽

Suzan Mohamed Talaat ◽

Rasha F. Bakry

Keyword(s):

Endometrial Cancer ◽

Microsatellite Instability ◽

Endometrial Carcinoma ◽

Mismatch Repair ◽

Tumor Grade ◽

Clinicopathological Parameters ◽

Small Subset ◽

Immunohistochemical Expression ◽

Mismatch Repair Proteins ◽

Mmr Proteins

BACKGROUND: Endometrial cancer (EC) is the fourth most common female cancer worldwide constituting 7% of cancer in women. It is a disease of older, postmenopausal women. The most of these patients have an identifiable source of excess estrogen, while in a small subset the pathogenesis is related to mismatch repair abnormality and lynch syndrome (LC). Mismatch repair behave as tumor suppressors and the most clinically relevant include MLH1, MSH2, MSH6, and PMS2. mutations in mismatch repair (MMR) results in a strong mutator phenotype known as microsatellite instability, which is a hallmark of LC-associated cancers. AIM: The aim of the study was to study microsatellite instability in endometrial cancer using the immunohistochemical expression of mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2). MATERIAL AND METHODS: Sixty EC cases were studied using MLH-1, MSH-2, MSH-6, and PMS-2 immunohistochemistry and their expression was correlated with different clinicopathologic parameters. RESULTS: A statistically significant relationship exists between MMR immunohistochemistry (IHC) proteins and tumor grade. Intact MMR proteins profile was associated with the lower tumor grade (31.3% were Grade 1 and 46.9% were Grade 2). Combined loss of MLH1/PMS2, combined loss of MSH2/MSH6, and isolated loss of PMS2 were also associated with the lower tumor grade while isolated loss of MSH6 was associated with the high tumor grade. However, no statistically significant correlation was found between MMR IHC proteins expression and the age of patients; tumor histopathological types, or FIGO stage. CONCLUSION: A statistically significant correlation between the tumor grade of EC cases and the MMR IHC proteins was found. Further studies are recommended to assess correlation between MMR proteins defect and different clinicopathological parameters of endometrial carcinoma.

Download Full-text