Analysis of p53/BAX/p16^ink4a/CDKN2 in Esophageal Squamous Cell Carcinoma: High BAX and p16^ink4a/CDKN2 Identifies Patients With Good Prognosis

Abstract

In this retrospective investigation, the combined analysis of BAX and p16(ink4a/CDKN2) shows subgroups in SCC of the esophagus with favorable (p16(ink4a/CDKN2)/BAX high expressing) or poor prognosis (loss of p16(ink4a/CDKN2)/loss of BAX). We suggest that such a multimarker analysis of apoptosis pathways could be useful for individualization of therapeutic strategies in the future, and suggest prospective studies to confirm these results.

Analysis of p53/BAX in primary colorectal carcinoma: Low BAX protein expression is a negative prognostic factor in UICC stage III tumors

“…33 In contrast, the inactivation of p53 by mutation does not necessarily result in a loss of BAX expression because additional factors seem to be involved in the regulation of BAX gene expression. 32 In line with our earlier observations in colorectal carcinoma, 13 esophageal squamous cell carcinoma 17 and breast carcinoma, 32 we did not observe a significant difference in BAX expression between the p53 wildtype and the p53 mutant tumors. The mutational status of p53 is reflected by the expression of p21 Cip/WAF-1 that is impaired in colorectal carcinomas with a mutant p53 indicating the dominant role of p53 in regulating p21 expression.…”

“…3,[7][8][9][10][11][12] We have shown previously that loss of BAX expression correlates with a poor prognosis in patients with hepatic metastases of colorectal cancer undergoing surgical resection of liver metastases. 13 Similar data were obtained in diffuse aggressive nonHodgkin-lymphoma, 14 ovarian, 15 pancreatic 16 and esophageal cancer 17 where reduced BAX expression was also observed to be a negative prognostic factor. Furthermore, we demonstrated that the restoration of BAX expression in breast cancer cell lines resulted in an increased sensitivity to DNA damaging agents.…”

“…13,17 This was especially relevant in the subgroup of patients with intact p53 gene. In consideration of these findings, we analyzed 116 primary colorectal adenocarcinomas to investigate whether the analysis of p53 and BAX status also defines a subgroup of patients with good prognosis in these patients with colorectal carcinoma.…”

“…In addition, defects in p53 downstream signaling effectors may impair both cell cycle arrest and induction of apoptosis by p53. 3,6,13,17 In addition to p53, therefore, we concentrated on BAX as a central downstream effector of p53 in apoptosis.…”

“…13,17,33 For antigen demasking after deparaffination, slides were boiled for 10 min in citrate buffer (0.01 mol/l, pH 6.0). For blocking of endogenous peroxidase, 3% H 2 O 2 was used and for inhibition of unspecific protein-proteininteractions, fish serum (Sea Block, Pierce Chemical, Rockford, IL) was applied.…”