Abstract
Clinical screening criteria, such as young age of endometrial cancer diagnosis and family history of signature cancers, have traditionally been used to identify women with Lynch Syndrome, which is caused by mutation of a DNA mismatch repair gene. Immunohistochemistry and microsatellite instability analysis have evolved as important screening tools to evaluate endometrial cancer patients for Lynch Syndrome. A complicating factor is that 15-20% of sporadic endometrial cancers have immunohistochemical loss of the DNA mismatch repair protein MLH1 and high levels of microsatellite instability due to methylation of MLH1. The PCR-based MLH1 methylation assay potentially resolves this issue, yet many clinical laboratories do not perform this assay. The objective of this study was to determine if clinical and pathologic features help to distinguish sporadic endometrial carcinomas with MLH1 loss secondary to MLH1 methylation from Lynch Syndrome-associated endometrial carcinomas with MLH1 loss and absence of MLH1 methylation. Of 337 endometrial carcinomas examined, 54 had immunohistochemical loss of MLH1. 40/54 had MLH1 methylation and were designated as sporadic, while 14/54 lacked MLH1 methylation and were designated as Lynch Syndrome. Diabetes and deep myometrial invasion were associated with Lynch Syndrome; no other clinical or pathological variable distinguished the 2 groups. Combining Society of Gynecologic Oncology screening criteria with these 2 features accurately captured all Lynch Syndrome cases, but with low specificity. In summary, no single clinical/pathologic feature or screening criteria tool accurately identified all Lynch Syndrome-associated endometrial carcinomas, highlighting the importance of the MLH1 methylation assay in the clinical evaluation of these patients.
Keywords: Lynch Syndrome, molecular diagnostics, MLH1 methylation, immunohistochemistry, endometrial cancer.
Current Pharmaceutical Design
Title:Utility of MLH1 Methylation Analysis in the Clinical Evaluation of Lynch Syndrome in Women with Endometrial Cancer
Volume: 20 Issue: 11
Author(s): Amanda S. Bruegl, Bojana Djordjevic, Diana L. Urbauer, Shannon N. Westin, Pamela T. Soliman, Karen H. Lu, Rajyalakshmi Luthra and Russell R. Broaddus
Affiliation:
Keywords: Lynch Syndrome, molecular diagnostics, MLH1 methylation, immunohistochemistry, endometrial cancer.
Abstract: Clinical screening criteria, such as young age of endometrial cancer diagnosis and family history of signature cancers, have traditionally been used to identify women with Lynch Syndrome, which is caused by mutation of a DNA mismatch repair gene. Immunohistochemistry and microsatellite instability analysis have evolved as important screening tools to evaluate endometrial cancer patients for Lynch Syndrome. A complicating factor is that 15-20% of sporadic endometrial cancers have immunohistochemical loss of the DNA mismatch repair protein MLH1 and high levels of microsatellite instability due to methylation of MLH1. The PCR-based MLH1 methylation assay potentially resolves this issue, yet many clinical laboratories do not perform this assay. The objective of this study was to determine if clinical and pathologic features help to distinguish sporadic endometrial carcinomas with MLH1 loss secondary to MLH1 methylation from Lynch Syndrome-associated endometrial carcinomas with MLH1 loss and absence of MLH1 methylation. Of 337 endometrial carcinomas examined, 54 had immunohistochemical loss of MLH1. 40/54 had MLH1 methylation and were designated as sporadic, while 14/54 lacked MLH1 methylation and were designated as Lynch Syndrome. Diabetes and deep myometrial invasion were associated with Lynch Syndrome; no other clinical or pathological variable distinguished the 2 groups. Combining Society of Gynecologic Oncology screening criteria with these 2 features accurately captured all Lynch Syndrome cases, but with low specificity. In summary, no single clinical/pathologic feature or screening criteria tool accurately identified all Lynch Syndrome-associated endometrial carcinomas, highlighting the importance of the MLH1 methylation assay in the clinical evaluation of these patients.
Export Options
About this article
Cite this article as:
Bruegl S. Amanda, Djordjevic Bojana, Urbauer L. Diana, Westin N. Shannon, Soliman T. Pamela, Lu H. Karen, Luthra Rajyalakshmi and Broaddus R. Russell, Utility of MLH1 Methylation Analysis in the Clinical Evaluation of Lynch Syndrome in Women with Endometrial Cancer, Current Pharmaceutical Design 2014; 20 (11) . https://dx.doi.org/10.2174/13816128113199990538
DOI https://dx.doi.org/10.2174/13816128113199990538 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Biology of Cox-2: An Application in Cancer Therapeutics
Current Drug Targets Antimicrobial, Antineoplastic and Cytotoxic Activities of Indole Alkaloids from Tabernaemontana divaricata (L.) R.Br.
Current Pharmaceutical Analysis Cyclophilin function in Cancer; lessons from virus replication
Current Molecular Pharmacology Function of miRNA in Controlling Drug Resistance of Human Cancers
Current Drug Targets Rho GTPase Effector Functions in Tumor Cell Invasion and Metastasis
Current Drug Targets Synthesis and Activity of Epothilone D
Current Drug Targets Toward The Rational Design of Cell Fate Modifiers Notch Signaling as a Target for Novel Biopharmaceuticals
Current Pharmaceutical Biotechnology Genetics Talks to Epigenetics? The Interplay Between Sequence Variants and Chromatin Structure
Current Genomics A Review of Coumarin Derivatives in Pharmacotherapy of Breast Cancer
Current Medicinal Chemistry Dual-Targeted Molecular Probes for Cancer Imaging
Current Pharmaceutical Biotechnology Recent Knowledge and New Pharmaceutical Products in Potential Alleviation of Endometriosis
Recent Patents on Inflammation & Allergy Drug Discovery Small Molecule Inhibitors of Multidrug Resistance Gene (MDR1) Expression: Preclinical Evaluation and Mechanisms of Action
Current Cancer Drug Targets Strategies that Target Tight Junctions for Enhanced Drug Delivery
Current Pharmaceutical Design Targeting CCK Receptors in Human Cancers
Current Topics in Medicinal Chemistry The Role of Aromatase Enzyme in Hormone Related Diseases and Plant- Based Aromatase Inhibitors as Therapeutic Regimens
Current Topics in Medicinal Chemistry Carbon Nanotubes in the Treatment of Skin Cancers: Safety and Toxic ological Aspects
Pharmaceutical Nanotechnology Inhibitors of Aldo-Keto Reductases AKR1C1-AKR1C4
Current Medicinal Chemistry On Electromagnetic Ablation of Biological Tissues: A Review
Recent Patents on Electrical Engineering Between Bench and Bed Side: PI3K Inhibitors
Current Molecular Pharmacology Texture Analysis in the Evaluation of COVID-19 Pneumonia in Chest X-Ray Images: A Proof of Concept Study
Current Medical Imaging