EXPRESSION OF BAX, A PRO-APOPTOTIC MEMBER OF THE BCL-2 FAMILY, IN ESOPHAGEAL SQUAMOUS-CELL CARCINOMA

Samples of normal esophageal squamous epithelium (n = 10), severe squa mous cell dyplasia (n = 22), carcinoma in situ (n = 15), invasive squa mous cell carcinoma (n = 172), lymph-node metastasis (n = 21) and 2 pe rmanent esophageal squamous cell carcinoma cell lines were analyzed im munohistochemically for Bax expression using a polyclonal anti-Bax ant ibody. Immunostaining was evaluated according to a score system (0-8 p oints) based on the percentage of positive tumor cells and the relativ e immunostaining intensity. Cytoplasmatic staining for Bax protein was found uniformly in all cell layers of the normal esophageal squamous epithelium, In contrast, a gradual loss of immunoreactivity for Bax wa s found in a fraction of pre-neoplastic and neoplastic lesions, Upon c omparison of the amount of Bax expression between the different types of lesion, however, no significant differences were found between seve re squamous cell dysplasias, carcinomas in situ, invasive carcinomas a nd lymph-node metastases, In both esophageal carcinoma cell lines, imm unoreactivity for Bax was found and confirmed by means of Northern blo t analysis. In invasive carcinomas, Bax immunoreactivity was inversely correlated with Bcl-2 expression (P = 0.0243) and decreased continuou sly with decreasing tumor differentiation (p = 0.0011). No correlation was found between Bax expression and the following parameters: depth of invasion, nodal status and tumor size, Bax expression had no influe nce on the post-operative survival of esophageal cancer patients. (C) 1997 Wiley-Liss, Inc.