Related Experiment Video

Updated: May 14, 2026

Immunostaining for DNA Modifications: Computational Analysis of Confocal Images
09:42

Immunostaining for DNA Modifications: Computational Analysis of Confocal Images

Published on: September 7, 2017

Promoter hypermethylation contributes to TIMP3 down-regulation in high stage endometrioid endometrial carcinomas

Lluis Catasus1, Cristina Pons, Josefina Muñoz

  • 1Department of Pathology, Hospital de la Santa Creu i Sant Pau, Institute of Biomedical Research, Autonomous University of Barcelona, Barcelona, Spain. lcatasus@santpau.cat

Histopathology
|February 6, 2013
PubMed
Abstract

Insights

Tissue inhibitor of metalloproteinases-3 (TIMP-3) promoter hypermethylation is linked to advanced endometrial cancer stages. This epigenetic silencing impacts TIMP-3 expression, potentially affecting tumor progression and prognosis in endometrial carcinomas.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Tissue inhibitor of metalloproteinases-3 (TIMP-3) expression is often reduced in cancers due to promoter hypermethylation.
  • The specific role of TIMP3 promoter hypermethylation in endometrial carcinomas and its prognostic implications remain largely unexplored.

Purpose of the Study:

  • To investigate the frequency and significance of TIMP3 promoter hypermethylation in endometrioid endometrial carcinomas.
  • To evaluate the correlation between TIMP3 hypermethylation, gene/protein expression, and clinicopathological features.

Main Methods:

  • Methylation-specific multiplex ligation-dependent probe amplification was used to assess TIMP3 promoter hypermethylation and copy number variations in 60 endometrial carcinoma cases.
  • TIMP3 transcript and protein expression levels were analyzed.

Main Results:

  • Loss of TIMP-3 protein expression was observed in 73% of tumors.
  • TIMP3 promoter hypermethylation occurred in 25% of cases, being more prevalent in advanced stages (II-IV) and tumors with deep myometrial invasion.
  • Simultaneous hypermethylation of MLH1 and TIMP3 promoters was noted, along with a correlation between TIMP3 methylation and microsatellite instability (MSI).

Conclusions:

  • TIMP3 promoter hypermethylation is associated with high-stage endometrioid endometrial tumors, particularly those with extrauterine spread.
  • While hypermethylation contributes to TIMP3 inactivation, other mechanisms like loss of heterozygosity are also involved.

More Related Videos

Tropomodulin 3 Overexpression as a Marker for Platinum Resistance and Immune Infiltration in Ovarian Cancer09:40

Tropomodulin 3 Overexpression as a Marker for Platinum Resistance and Immune Infiltration in Ovarian Cancer

Published on: August 2, 2024

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors06:07

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors

Published on: August 5, 2022

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
Phase II Reactions: Methylation Reactions01:17

Phase II Reactions: Methylation Reactions

Methylation is a phase II biotransformation process involving the attachment of a methyl group to a substrate. Enzymes known as methyltransferases orchestrate this reaction.
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...