The Prognostic Significance of Apoptotic Protease Activating Factor (Apaf-1) Protein Expression in Colon Adenocarcinoma Tissue-Preliminary Report

Abstract

Background: The Apoptotic protease activating factor 1 (Apaf-1) protein, as one of the factors involved in the activation of the mitochondrial apoptotic pathway, plays an important role in cancer biology. Apaf-1 expression in tumour cells has been shown to be downregulated, with significant implications for tumour progression. Hence, we investigated the expression of Apaf-1 protein in the Polish population of patients with colon adenocarcinoma without any therapy prior to radical surgery. Moreover, we assessed the relation between Apaf-1 protein expression and the clinicopathological factors. The prognostic activity of this protein was analyzed in relation to 5-year survival of patients. In order to show the localization of Apaf-1 protein at the cellular level, the immunogold labelling method was used.

Methods: The study was conducted using the colon tissue material from patients with histopathologically confirmed colon adenocarcinoma. Immunohistochemical expression of Apaf-1 protein was performed using Apaf-1 antibody at dilution 1:600. The associations between the immunohistochemistry (IHC) expression of Apaf-1 and clinical parameters were analyzed using the Chi2 test and Chi2Yatesa test. Kaplan-Meier analysis and the log-rank test were used to verify the relationship between the intensity of Apaf-1 expression and 5-year survival rate of patients. The results were considered statistically significant when p < 0.05.

Results: Apaf-1 expression was evaluated by immunohistochemical staining in whole tissue sections. Thirty-nine (33.23%) samples had strong Apaf-1 protein expression and 82 (67.77%) samples were characterized by low expression. The high expression of Apaf-1 was clearly correlated with the histological grade of the tumour (p = 0.001), proliferating cell nuclear antigen (PCNA) immunohistochemical expression (p = 0.005), age (p = 0.015), depth of invasion (p < 0.001) and angioinvasion (p < 0.001). The 5-year survival rate was significantly higher in the group of patients with high expression of this protein (log-rank, p < 0.001).

Conclusions: We can conclude that Apaf-1 expression is positively correlated with reduced survival of colon adenocarcinoma patients.

Keywords: 5-year survival rate; apoptosis; colon adenocarcinoma; immunogold labelling; immunohistochemistry; prognostic marker.