MDM2 GENE AMPLIFICATION AND EXPRESSION IN NON-SMALL-CELL LUNG-CANCER - IMMUNOHISTOCHEMICAL EXPRESSION OF ITS PROTEIN IS A FAVORABLE PROGNOSTIC MARKER IN PATIENTS WITHOUT P53 PROTEIN ACCUMULATION

MDM2 is an oncoprotein that inhibits p53 tumour-suppressor protein. Am plification of the MDM2 gene and overexpression of its protein have be en observed in some human malignancies, and these abnormalities have a role in tumorigenesis through inactivation of p53 function. To determ ine the clinicopathological and prognostic value of MDM2 abnormalities in non-small-cell lung cancer (NSCLC), MDM2 gene amplification and it s protein expression status were analysed in surgically resected mater ials. MDM2 gene amplification was detected in only 2 (7%) of the 30 te sted patients. MDM2 protein was found immunohistochemically in a total of 48 (24%) of the 201 patients. MDM2 protein was slightly frequently observed in patients with adenocarcinoma, but its presence or absence was not associated with clinicopathological factors such as T-factor, N-factor, stage, tumour size, differentiation or p53 protein status. Overall, MDM2-positive patients tended to have a better prognosis (P=0 .062). In particular, among immunohistochemically p53-negative patient s (n=110), those with positive MDM2 protein expression showed signific antly better prognosis (P=0.039) and, in a multivariate analysis, MDM2 protein status was a favourable prognostic factor (P=0.037). In contr ast, among p53-positive patients (n=91), there was no difference in pr ognosis depending on MDM2 protein status. Thus, in the NSCLC patients studied, MDM2 gene amplification was a minor event, but expression of its protein, which was often observed immunohistochemically, was a fav ourable prognostic marker, especially among patients without p53 prote in accumulation, Further study is needed to determine how MDM2 protein expression results in a better prognosis.