Abrupt loss of MLH1 and PMS2 expression in endometrial carcinoma: molecular and morphologic analysis of 6 cases

The American Journal of Surgical Pathology
Rish K PaiAndres R Roma

Abstract

Given that endometrial cancer (EC) is often the sentinel cancer for female Lynch syndrome patients, we have successfully implemented universal screening of ECs and have previously shown that this is the preferred method to identify these patients. However, during the course of universal screening of EC, we encountered 6 cases with an unusual pattern of mismatch-repair protein immunohistochemistry that has not been previously described in this setting. In these 6 cases, there was an abrupt loss of MLH1 and PMS2 expression in a portion of the tumor. In 3 cases, marked histologic differences were identified between the areas of the tumor with retained expression and areas with loss of expression. In 2 cases, the areas with loss of expression were of higher grade (1 demonstrated solid growth and the other demonstrated increased nuclear atypia with diffuse p53 expression). In 4 tumors, histologic features associated with microsatellite instability (MSI) were present, including increased intraepithelial lymphocytes. The areas with loss of and retained MLH1/PMS2 expression were separately microdissected and assessed for MSI and MLH1 promoter methylation. The areas with loss of MLH1 and PMS2 more commonly demonstrated MSI compared with...Continue Reading

References

Sep 1, 1999·Genes, Chromosomes & Cancer·W S Samowitz, M L Slattery
Nov 6, 2004·Disease Markers·Henry T Lynch, Jane F Lynch
Jul 30, 2009·Journal of Clinical Pathology·K Garg, R A Soslow
Feb 12, 2011·Seminars in Diagnostic Pathology·Robert A Soslow
Oct 6, 2011·Archives of Pathology & Laboratory Medicine·Katherine B Geiersbach, Wade S Samowitz
Jul 20, 2012·Nature·UNKNOWN Cancer Genome Atlas Network
Jun 7, 2014·Molecular Cell·Hariharan EaswaranStephen B Baylin

❮ Previous
Next ❯

Citations

May 5, 2017·Epigenomics·Carla BartoschCarmen Jerónimo
May 18, 2016·The American Journal of Surgical Pathology·Jaclyn C WatkinsLynette M Sholl
Feb 27, 2019·International Journal of Gynecological Pathology : Official Journal of the International Society of Gynecological Pathologists·David B ChapelRicardo R Lastra
Dec 8, 2019·Virchows Archiv : an International Journal of Pathology·Christoph FrauneStefan Steurer
Mar 15, 2016·The American Journal of Surgical Pathology·Rish K Pai, Reetesh K Pai
Jan 12, 2020·Gynecologic Oncology·Christoph FrauneEike Burandt
Jan 1, 2017·Annals of Oncology : Official Journal of the European Society for Medical Oncology·E StellooT Bosse

❮ Previous
Next ❯

Methods Mentioned

BETA
electrophoresis
biopsy
hysterectomy

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.