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From the Department of Thoracic Surgery and Department V of
Oncology,*
Kitano Hospital, Tazuke Kofukai Medical Research
Institute, Osaka, Japan; the Second Department of Internal
Medicine,
Ehime University School of Medicine,
Ehime, Japan; the First Department of
Surgery,
Kinki University School of Medicine,
Osaka, Japan; and the Department of Surgery,§
Osaka Medical Center for Cancer and Cardiovascular Diseases,
Osaka, Japan
Recent investigations have revealed that mutations of the
loop-sheet-helix motif of p53 is a significant factor for a
poor prognosis in patients with non-small-cell lung cancer (NSCLC). To
clarify this mechanism, bcl-2 and bax expression were evaluated
in relation to mutations of p53. Tumor tissues of 203
patients with NSCLC were analyzed. Immunohistochemistry was performed
to evaluate bcl-2 and bax expression, and polymerase chain
reaction single-strand conformation polymorphism following direct
sequencing was performed to investigate p53 status. A total
of 79 carcinomas were bcl-2 positive, 146 carcinomas were bax
positive, and 72 carcinomas had missense mutations of
p53. There was no difference in bcl-2 expression in
relation to p53 status. On the other hand, tumors
with structural mutations of p53 had significantly lower
expression of bax than those with wild-type p53
(P = 0.0026). In contrast, tumors with
mutations of the loop-sheet-helix motif of p53 had
significantly higher expression of bax than those with wild-type
p53 (P = 0.0236). The frequency of a
bcl-2/bax ratio of
1 was significantly lower in tumors with mutations
of the loop-sheet-helix motif than that in tumors with wild-type
p53 (P = 0.0240). The bcl-2/bax ratio
status was a significant factor for a prognosis in patients with NSCLC
(P = 0.0083). Mutations of the loop-sheet-helix motif
of p53 were correlated with overexpression of bax,
while other mutations of p53 were correlated with low
levels of bax expression. This variation in pattern of bax expression
in relation to mutant p53 might reflect the biological
behavior of tumors in patients with bcl-2-positive NSCLC.
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