REGULATORS OF PROLIFERATION AND APOPTOSIS IN CARCINOMA OF THE LARYNX

Expression of interrelated gene products regulating cell proliferation and apoptosis may be disordered in squamous cell carcinoma (SCC) of t he larynx compared with normal squamous mucosa, Certain of these abnor malities, alone or in combination, may be of prognostic significance i n low-stage carcinomas of the larynx. A retrospective study of archiva l material was made. Expression of the Bcl-2 family of apoptosis-relat ed genes (bcl-2, bcl-X, mcl-1, and bax) and the proliferation- and apo ptosis-related genes p53 and cyclin D-1 were determined in 40 low-T-st age laryngeal carcinomas and in uvular epithelium from patients withou t SCC, Among the antiapoptotic members of the Bcl-2 family, Bcl-X and Mcl-1 showed more intense and widespread staining than Bcl-2 itself in both normal squamous mucosa and SCC, The well-ordered expression patt erns of Bcl-2-related proteins found in normal epithelium were lost in SCC, and patterns of expression varied widely among individual tumors . Also, mean expression levels for Bax and cyclin D-1 were significant ly lower than in normal epithelium (P = .036 and P = .009, respectivel y), whereas expression of p53 was higher in tumors (P = .034), Express ion of Bcl-X and Mcl-1 was greater in poorly differentiated than in we ll-differentiated tumors (P = .014 and P = .031, respectively). No ass ociations were seen between marker expression patterns and clinical ou tcome in this group of patients. Bcl-x and Mcl-1 appear to be the most abundantly expressed antiapoptotic proteins of the Bcl-2 family in bo th normal squamous mucosa and SCC of the larynx, Multiple genes regula ting proliferation and apoptosis are expressed abnormally in laryngeal SCC compared with normal epithelium. in particular, loss or measurabl e decrease in expression of the proapoptotic protein Bax in tumors may contribute to the deranged growth control of SCC, Further study is ne eded to evaluate the prognostic significance of particular patterns of disordered expression of proteins regulating proliferation and apopto sis in SCC of different head and neck sites.