Analysis of p53/BAX/p16(ink4a/CDKN2) in esophageal squamous cell carcinoma: High BAX and p16(nk4a/CDKN2) identifies patients with good prognosis

Purpose: We have previously shown that loss of BAX expression is a negative prognostic factor in metastatic colorectal cancer. In the present study, w e addressed the prognostic relevance of BAX and its upstream regulator p53 in squamous cell carcinoma (SCC) of the esophagus. Analysis of p16(ink4a/CD KN2) was included because p16(ink4a/CDKN2) and p53 were shown previously to cooperate during induction of cell cycle arrest and apoptosis. Patients and Methods: Retrospective analysis of 53 patients with curative i ntended RO resection of esophageal SEC was done. protein expression of BAX, p53, and p16(ink4a/CDKN2) was investigated by immunohistochemistry. in add ition, tumor DNA was screened for BAX frameshift mutations by fragment leng th analysis and for p53 mutations by single-strand conformation polymorphis m-polymerase chain reaction. Results: Overali median survival was 13.7 months. patients with high BAX pr otein expression had a median survival of 19.5 months versus 8.0 months wit h low BAX expression (P <.005). High p16(ink4a/CDKN2) protein expression wa s associated with a median survival of 23.8 months versus 9.7 months with l ow p16(ink4a/CDKN2) (P = .011). The best survival (median, 45.8 months) was seen in a subgroup of 12 patients whose tumors bore the combination of bot h favorite phenotypes tie, high BAX and high p16(ink4a/CDKN2) protein expre ssion). Conclusion: In this retrospective investigation, the combined analysis of B AX and p16(ink4a/CDKN2) shows subgroups in SCC of the esophagus with favora ble (p16(ink4a/CDKN2)/BAX high expressing) or poor prognosis (loss of p16(i nk4a/CDKN2)/loss of BAX). We suggest that such a multimarker analysis of ap optosis pathways could be useful for individualization of therapeutic strat egies in the future, and suggest prospective studies to confirm these resul ts. <(c)> 2001 by American Society of Clinical Oncology.