The prognostic significance of p21 and Her-2 gene expression and mutation/polymorphism in patients with gastric adenocarcinoma

Abstract

Analyses of gene expression status and genetic polymorphisms are methods to identify novel histopathological prognostic factors. In patients with gastric cancer, some cell cycle regulators p53, p21, p27 and Her-2 oncogene have been proposed as prognostic factors. We aimed to investigate the expression and mutation/polymorphism of p21 and Her-2 and also relationship between that genes status and histopathological factors and prognosis in patients with gastric cancer. Forty-four patients with locally advanced gastric cancer were analyzed in this study from January 2000 to December 2008. Clinicopathological parameters, expression and mutation/polymorphism of p21 and Her-2 results were used to predict disease-free survival and overall survival. The positive expression of p21 and Her-2 was observed in 61.4 % (n = 27) and 9.1 % (n = 4) of all 44 tumors, respectively. p21 gene mutation and Her-2 gene polymorphism were detected in 20 % (n = 11) and 2.3 % (n = 1, II phenotype) of cases, respectively. The negative expression of p21 was correlated significantly with diffuse and undifferential type histologies, whole gastric involvement and positive vascular/neural invasion. The median survival rate of patients with negative expression was significantly poorer than that of patients with positive expression of p21 (17 vs. 27 months, p = 0.01, cox regression). p21 mutation was significantly higher in patients with diffuse (p = 0.03) and undifferential (p = 0.02) type histologies. There was no statistically significant association between histopathological parameters and Her-2 gene polymorphism/expression. The negative expression of p21 correlates with disease survival and may be a poor prognostic factor in patients with resected gastric cancer treated with adjuvant chemotherapy.

Expression of CD24, p21, p53, and c‐myc in alpha‐fetoprotein‐producing gastric cancer: Correlation with clinicopathologic characteristics and survival

“…Our data showed that p21 expression was significantly associated with poor survival. This result was not consistent with the previous researches reported in common gastric cancer [28][29][30]. It was possible that the difference could be attributed to the different biological behavior between AFP-producing gastric cancer and common gastric cancer.…”

“…Additionally, p21 interferes with PCNA-dependent DNA polymerase activity, resulting in the inhibition of the DNA replication and modulation of a variety of PCNAdependent DNA repair processes [25]. Some studies have investigated the relationship between p21 and gastric cancer [26][27][28][29][30]. Gamboa-Dominguez et al [28] found that patients with positive expression for p21 had a favorable prognosis.…”

Hepatocyte Expression of the Senescence Marker p21 Is Linked to Fibrosis and an Adverse Liver-Related Outcome in Alcohol-Related Liver Disease

“…Thus, it plays a vital role in induction and maintenance of cellular senescence. Recent studies have demonstrated the potential utility of p21 expression as a prognostic marker in malignant disease [11]. However, less is known of the prognostic implications of p21 expression in chronic inflammatory conditions such as ALD.…”

Can increased or decreased COX2 and P21 expression be used in illness monitoring of gastric cancer and its potential precursor lesions?

“…Grade and intensity of P21 expression were low and similar in atrophic gastritis and intestinal metaplasia groups. While Gamboa-Dominguez (21) and Kouraklis et al (22) found a positive correlation between P21 expression and survival, other studies showed that the loss of P21 expression in cancer was associated with poor prognosis (18,23).…”