p53, Cyclin-D1, β-catenin, APC and c-myc in Tumor Tissue from Colorectal and Gastric Cancer Patients with Suspected Lynch Syndrome by the Bethesda Criteria

Asian Pac J Cancer Prev. 2020 Feb 1;21(2):343-348. doi: 10.31557/APJCP.2020.21.2.343.

Abstract

Colorectal cancer (CRC) is one of the most frequent neoplasms worldwide, and up to 15% have a family history. Lynch syndrome (LS) is a hereditary cause of CRC and gastric (GC). Individuals with LS have mutations in mismatch genes repair. p53, cyclin D1, β-catenin, APC and c-myc proteins are involved in the cell cycle and carcinogenesis.

Objective: To study the expression of p53, Cyclin D1, β-catenin, APC and c-myc proteins in patients with CRC and GC with at least one of the Bethesda positive criteria. Compare the expression of these proteins with the presence or absence of expression of the DNA repair proteins.

Patients and methods: We included 70 individuals with CRC or GC with at least one of the Bethesda positive criteria. Protein expression of MLH1, MSH2, MSH6, PMS2, p53, cyclin D1, β-catenin, APC and c-myc were analized by immunohistochemistry tumours tissues.

Results: Deficient expression of MLH1, MSH2, MSH6 and PMS2 were respectively 38.7%; 17.7%; 26.22% and 48.38%. We found a negative association between deficiency of PMS2 and age, and positive association between PMS2 deficiency and APC positive. The positive imunoexpression of APC increases by 4 times the chance of having deficiency of PMS2.

Conclusions: Patients with loss of expression of PMS2 had a higher risk of mutation or deletion of APC and tumours with positive immunoexpression of cyclin D1 had an increased risk of loss of expression of MSH2. These results suggest that tumours with loss of expression of DNA repair proteins had a higher loss of cell control cycle.<br />.

Keywords: Gastric cancer; Lynch syndrome; colorectal cancer; immunohistochemistry.

MeSH terms

  • Adenomatous Polyposis Coli Protein / metabolism*
  • Biomarkers, Tumor / metabolism
  • Brazil / epidemiology
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / epidemiology
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms, Hereditary Nonpolyposis / physiopathology*
  • Cyclin D1 / metabolism*
  • DNA Repair Enzymes / metabolism
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Retrospective Studies
  • Stomach Neoplasms / diagnosis*
  • Stomach Neoplasms / epidemiology
  • Stomach Neoplasms / metabolism
  • Tumor Suppressor Protein p53 / metabolism*
  • beta Catenin / metabolism*

Substances

  • APC protein, human
  • Adenomatous Polyposis Coli Protein
  • Biomarkers, Tumor
  • CCND1 protein, human
  • CTNNB1 protein, human
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • beta Catenin
  • Cyclin D1
  • DNA Repair Enzymes