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Microsatellite Alterations and Protein Expression of 5 Major Tumor Suppressor Genes in Gastric Adenocarcinomas

Won Hyuk Choi1, Sookhyun Lee2, Sungjin Cho3

  • 1Department of Surgery, Hallym University College of Medicine, Seoul, Korea.

Translational Oncology
|November 25, 2017
PubMed
Abstract

Insights

Loss of heterozygosity (LOH) and protein expression of tumor suppressor genes (TSGs) are linked to gastric adenocarcinoma (GC) progression. These genetic and protein alterations, particularly 17p13 LOH and p53 expression, may serve as useful prognostic indicators for GC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Gastric adenocarcinoma (GC) is a significant global health concern.
  • Major tumor suppressor genes (TSGs) are crucial in regulating cell growth and preventing tumor development.
  • Alterations in TSGs are implicated in the pathogenesis of various cancers, including GC.

Purpose of the Study:

  • To investigate the loss of heterozygosity (LOH) and protein expression of five key TSGs (p16, PTEN, Rb, E-cadherin, and p53) in GC.
  • To analyze the correlation between LOH, protein expression, and clinicopathological factors in GC patients.

Main Methods:

  • Loss of heterozygosity (LOH) analysis using polymerase chain reaction (PCR) with 15 polymorphic microsatellite markers across five chromosomes harboring TSGs.
  • Immunohistochemistry (IHC) to evaluate the protein expression levels of p16, PTEN, Rb, E-cadherin, and p53.
  • Analysis of 100 surgically resected GC tumors.

Main Results:

  • LOH was observed in 83% of GC cases, with specific frequencies for 9p21 (26%), 10q23 (31%), 13q14 (24%), 16q22 (22%), and 17p13 (35%).
  • Protein expression levels for p16, PTEN, Rb, E-cadherin, and p53 were 31%, 39%, 28%, 32%, and 46%, respectively.
  • Advanced GC stages showed significantly higher rates of 17p13 LOH and p53 expression. LOH and protein expression of these TSGs correlated with tumor grade, lymph node metastasis, and overall stage.

Conclusions:

  • LOH and altered protein expression of TSGs play significant roles in GC carcinogenesis and invasion.
  • LOH and IHC evaluation of TSGs can serve as valuable clinical biomarkers for predicting GC patient prognosis.
  • Specifically, 17p13 LOH and p53 protein expression are identified as simple yet effective clinical evaluation tools for GC.

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