Heterogeneous distribution of P53 immunoreactivity in human lung adenocarcinoma correlates with MDM2 protein expression, rather than with P53 gene mutation
T. Koga et al., Heterogeneous distribution of P53 immunoreactivity in human lung adenocarcinoma correlates with MDM2 protein expression, rather than with P53 gene mutation, INT J CANC, 95(4), 2001, pp. 232-239
Although the timer suppressor p53 protein (P53) immunoreactivity and its ge
ne (p53) mutation were reported to be significant prognostic indicators for
human lung adenocarcinomas, little is known regarding the relationship bet
ween the heterogeneous distribution of P53 and its genetic status in each t
umor focus and the clinicopathological significance. To determine how P53 i
s heterogeneously stabilized in patients, we compared P53 expression to bot
h the p53 allelic mutation in exon 2 similar to 9 by polymerase chain react
ion-single strand conformation polymorphism using microdissected DNA fracti
ons, and the immunohistochemical MDM2 expression. Of the 48 positive to P53
in 118 lung adenocarcinomas examined, 10 with heterogeneous P53 expression
were closely examined. The higher P53 expression foci in 7 of 10 cases wer
e less differentiated, histologically in respective cases, and were frequen
tly associated with fibrous stroma. Two had genetic mutations in exon 7 of
the P53 gene in both the high and low P53 expression foci of cancer tissue
indicating no apparent correlation between heterogeneous P53 expression and
the occurrence of gene mutation. Immunohistochemical expression of MDM2 wa
s significantly tower in high P53 expression areas (p < 0.05, the mean labe
ling indices of high and low P53 expression areas being 4.2 +/- 5.4% and 13
.6 +/- 12.2%, respectively). In addition, among all the 118 cases examined,
MDM2 expression was significantly suppressed in cases of p53 gene mutation
, simultaneously with P53 overexpression, as compared with cases without bo
th the p59 mutation and expression (p < 0.001), These findings suggest that
the heterogeneous stabilization of P53 in human lung adenocarcinomas could
be partly due to suppressed MDM2 expression. The overexpression of non-mut
ated P53 may afford a protective mechanism in human lung adenocarcinomas. (
C) 2001 Wiley-Liss, Inc.