MDM2 gene amplification and expression in non-small-cell lung cancer: immunohistochemical expression of its protein is a favourable prognostic marker in patients without p53 protein accumulation.
MDM2 is an oncoprotein that inhibits p53 tumour-suppressor protein. Amplification of the MDM2 gene and overexpression of its protein have been observed in some human malignancies, and these abnormalities have a role in tumorigenesis through inactivation of p53 function. To determine the clinicopathological and prognostic value of MDM2 abnormalities in non-small-cell lung cancer (NSCLC), MDM2 gene amplification and its protein expression status were analysed in surgically resected materials. MDM2 gene amplification was detected in only 2 (7%) of the 30 tested 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 patients (n = 110), those with positive MDM2 protein expression showed significantly better prognosis (P = 0.039) and, in a multivariate analysis, MDM2 protein status was a favourable prognostic factor (P = 0.037). In contrast, among p53-positive patients (n = 91), there was no difference in prognosis 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 favourable prognostic marker, especially among patients without p53 protein accumulation. Further study is needed to determine how MDM2 protein expression results in a better prognosis.
Higashiyama
M
M
Department of Thoracic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases (formerly, Center for Adult Diseases, Osaka), Higashinariku, Japan.
Doi
O
O
Kodama
K
K
Yokouchi
H
H
Kasugai
T
T
Ishiguro
S
S
Takami
K
K
Nakayama
T
T
Nishisho
I
I
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009687:Nuclear Proteins; D017354:Point Mutation; D011184:Postoperative Period; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2