The prognostic significance of p53, Bax, Bcl-2 and cyclin E protein overexpression in colon cancer - an immunohistochemical study using the tissue microarray technique

Rom J Morphol Embryol. 2016;57(1):81-9.

Abstract

In colon cancer, biological markers continue to have a limited prognostic value, the results being controversial. Studies of cell-cycle regulatory proteins and anti-apoptotic proteins aim to identify groups of patients that develop more aggressive tumors and might benefit from an individualized therapy management. The present study evaluates the prognostic role of the p53, Bax, Bcl-2 and cyclin E immunoexpression in colon cancer, using the tissue microarray (TMA) method. Tissue samples were obtained from 31 patients operated for colon cancer, embedded in TMA paraffin blocks and immunohistochemically stained for p53, Bax, Bcl-2 and cyclin E. We evaluated the relationship between the overexpression of these proteins and the clinico-pathological parameters, as well as the effect of these molecular markers on the survival rate. 65.22% of the patients were p53 positive, 39.13% Bcl-2 positive, 78.26% Bax positive and 34.78% cyclin E positive. Bcl-2(+) patients had significantly better differentiated tumors (p=0.043). Significantly poorly differentiated tumors were: Bax(+) patients (p=0.031), Bcl-2(-)÷p53(-) patients (p=0.042), Bcl-2(-)÷Bax(+) patients (p=0.029), and Bcl-2(-)÷p53(-)÷Bax(+) patients (p=0.016). The individual expression of the studied proteins did not influence the survival rate. A significantly lower survival rate was found in the following groups of patients: Bcl-2(-)÷p53(-) (40% vs. 83.3%, p=0.027), p53(-)÷Bax(+) (40% vs. 83.3%, p=0.027), Bcl-2(-)÷p53(-)÷Bax(+) (25% vs. 84.2%, p=0.003). The current study identified groups of patients with a significantly lower survival rate, which consequently are at an increased risk to develop tumors with a more aggressive biological behavior.

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology
  • Cyclin E / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Oncogene Proteins / metabolism*
  • Prognosis
  • Tissue Array Analysis*
  • Tumor Suppressor Protein p53 / metabolism*
  • bcl-2-Associated X Protein / metabolism*

Substances

  • Biomarkers, Tumor
  • CCNE1 protein, human
  • Cyclin E
  • Oncogene Proteins
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein