We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
PURITAN MEDICAL

Download Mobile App




Lynch Syndrome Screening by IHC Leads to Mutation Studies

By LabMedica International staff writers
Posted on 24 Oct 2019
Print article
Image: A and B, Mucinous adenocarcinoma of colon and indeterminate PMS2 immunohistochemistry staining. C and D, Poorly differentiated carcinoma of colon and indeterminate MLH1 staining. E and F, Endometrial carcinoma and focal MSH6 staining (Photo courtesy of University of Texas Southwestern Medical Center).
Image: A and B, Mucinous adenocarcinoma of colon and indeterminate PMS2 immunohistochemistry staining. C and D, Poorly differentiated carcinoma of colon and indeterminate MLH1 staining. E and F, Endometrial carcinoma and focal MSH6 staining (Photo courtesy of University of Texas Southwestern Medical Center).
Lynch syndrome or hereditary nonpolyposis colorectal cancer is an autosomal dominant genetic condition that is associated with a high risk of colon cancer, as well as other cancers including endometrial cancer, ovary, stomach, small intestine, hepatobiliary tract, upper urinary tract, brain, and skin.

Immunohistochemical expression of mismatch repair (MMR) protein is a well-accepted method for routine screening for Lynch syndrome (LS) with relatively high sensitivity and specificity. Occasionally, however, immunohistochemistry (IHC) can yield an equivocal result with poor reproducibility and the potential for misdiagnosis.

A pathologist and a geneticist from the University of Texas Southwestern Medical Center (Dallas, TX, USA) retrospectively analyzed the data on MMR (MLH1, PMS2, MSH2, and MSH6) IHC results from their database of 479 patients with colorectal cancer (CRC) and endometrial cancer (EC) who were screened for LS between September 2011 and August 2013. Mismatch repair protein IHC was performed prospectively in all patients with a tissue diagnosis of CRC or EC before 70 and 50 years of age, respectively.

Semi-quantitative scoring of MMR IHC was performed by image analysis in 479 cases, of which 380 were colorectal and 99 endometrial cancers. Scores of 10% or more, less than 10%, and 0% were used as cutoffs for retained, indeterminate, and loss of expression, respectively. Negative and indeterminate IHC results were confirmed by mutational studies. The automated cell imaging system consisted of an automated robotic bright-field microscope module and a Windows NT–based software interface that digitizes the IHC-stained slide, and digital images were displayed on a computer screen and analyzed by proprietary software. Confirmatory germline testing was initiated after counseling the patients about the abnormal IHC results and obtaining their permission for further genetic testing.

The scientists reported that 418/479 cases (87.2%) were reported as retained expression, 45 (9.3%) as loss of expression, and 16 (3.3%) as indeterminate expression. Fifteen of 45 (33.3%) and eight of 16 (50%) with loss and indeterminate expression, respectively, were found to have Lynch syndrome by germline studies. The overall frequency of Lynch syndrome in the patient population was 4.8% (23/479), and 34.7% of these (8/23) were associated with indeterminate IHC expression. In the indeterminate group, MLH1 germline mutation was the most frequent (6/13; 46.2%), followed by MSH6 (4/13; 30.7%).

The authors concluded that their findings provided further evidence that indeterminate IHC should be further investigated for possible MMR germline mutation. Guidelines for interpretation of MMR IHC and the establishment of more objective criteria for defining indeterminate results are important to improve the sensitivity and specificity of the IHC assay. The study was published in the October 2019 issue of the journal Archives of Pathology and Laboratory Medicine.

Related Links:
University of Texas Southwestern Medical Center

Platinum Member
COVID-19 Rapid Test
OSOM COVID-19 Antigen Rapid Test
Specimen Collection & Transport
POCT Fluorescent Immunoassay Analyzer
FIA Go
New
Gold Member
Systemic Autoimmune Testing Assay
BioPlex 2200 ANA Screen with MDSS

Print article

Channels

Clinical Chemistry

view channel
Image: Reaching speeds up to 6,000 RPM, this centrifuge forms the basis for a new type of inexpensive, POC biomedical test (Photo courtesy of Duke University)

POC Biomedical Test Spins Water Droplet Using Sound Waves for Cancer Detection

Exosomes, tiny cellular bioparticles carrying a specific set of proteins, lipids, and genetic materials, play a crucial role in cell communication and hold promise for non-invasive diagnostics.... Read more

Molecular Diagnostics

view channel
Image: The study showed the blood-based cancer screening test detects 83% of people with colorectal cancer with specificity of 90% (Photo courtesy of Guardant Health)

Blood Test Shows 83% Accuracy for Detecting Colorectal Cancer

Colorectal cancer is the second biggest cause of cancer deaths among adults in the U.S., with forecasts suggesting 53,010 people might die from it in 2024. While fewer older adults are dying from this... Read more

Hematology

view channel
Image: The Gazelle Hb Variant Test (Photo courtesy of Hemex Health)

First Affordable and Rapid Test for Beta Thalassemia Demonstrates 99% Diagnostic Accuracy

Hemoglobin disorders rank as some of the most prevalent monogenic diseases globally. Among various hemoglobin disorders, beta thalassemia, a hereditary blood disorder, affects about 1.5% of the world's... Read more

Microbiology

view channel
Image: The new platform is designed to perform blood-based diagnoses of nontuberculosis mycobacteria (Photo courtesy of 123RF)

New Blood Test Cuts Diagnosis Time for Nontuberculous Mycobacteria Infections from Months to Hours

Breathing in nontuberculous mycobacteria (NTM) is a common experience for many people. These bacteria are present in water systems, soil, and dust all over the world and usually don't cause any problems.... Read more

Industry

view channel
Image: These new assays are being developed for use on the recently introduced DxI 9000 Immunoassay Analyzer (Photo courtesy of Beckman Coulter)

Beckman Coulter and Fujirebio Expand Partnership on Neurodegenerative Disease Diagnostics

Beckman Coulter Diagnostics (Brea, CA, USA) and Fujirebio Diagnostics (Tokyo, Japan) have expanded their partnership focused on the development, manufacturing and clinical adoption of neurodegenerative... Read more
Copyright © 2000-2024 Globetech Media. All rights reserved.