Differential expression of metallothionein and p21 in gastric cancer and some precursor lesions

Eur Rev Med Pharmacol Sci. 2022 May;26(9):3100-3108. doi: 10.26355/eurrev_202205_28727.

Abstract

Objective: Gastric cancer (GC) is a heterogeneous disease with molecular diversity between and within tumors; therefore, searching for altered genes within this cancer is mandatory to reach the proper individualized targeted therapy. Expressions of Metallothionein (MT) and p21 are not uniform in various types of cancers and their predictive value in GC is controversial. This study aimed to assess the role of MT and p21 in intestinal-type GC and some of its precursor lesions.

Materials and methods: Immunohistochemical staining for MT and p21 was applied on paraffin blocks belonging to 30 GCs and 51 benign gastric lesions/precancerous lesions [33 chronic gastritis and 18 chronic gastritis with gastric intestinal metaplasia (GIM)]; 27 of them were associated with H. pylori infection.

Results: MT expression was dramatically increased while p21 expression was dramatically decreased from chronic gastritis to GIM to GC. In precancerous lesions, H. pylori-positive cases had significantly higher MT expression and lower p21 expression compared to H. pylori-negative cases. In GCs, decreased expression of both MT and p21 was associated with high-grade and advanced-stage cancers.

Conclusions: Both MT and p21 may have a role in the development and progression of GC, and both proteins may be useful for selecting targeted therapy for GC patients.

MeSH terms

  • Cyclin-Dependent Kinase Inhibitor p21 / biosynthesis
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / pathology
  • Gastritis / metabolism
  • Gastritis / microbiology
  • Gastritis / pathology
  • Helicobacter Infections / metabolism
  • Helicobacter Infections / pathology
  • Helicobacter pylori / isolation & purification
  • Humans
  • Metallothionein* / biosynthesis
  • Metallothionein* / genetics
  • Metaplasia / metabolism
  • Metaplasia / pathology
  • Precancerous Conditions* / metabolism
  • Precancerous Conditions* / microbiology
  • Precancerous Conditions* / pathology
  • Stomach Neoplasms* / metabolism
  • Stomach Neoplasms* / microbiology
  • Stomach Neoplasms* / pathology

Substances

  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Metallothionein