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MAP Kinase Overexpressed in Never-Smokers With Lung Cancer

MAP Kinase Overexpressed in Never-Smokers With Lung Cancer

ISTANBUL, Turkey--In a study
investigating possible molecular abnormalities
in nonsmokers with lung adenocarcinoma,
a team of French researchers
has found that never-smokers significantly
overexpress the MAP (mitogen
activated protein) kinases P38 and JNK
(c-Jun N-terminal kinase), compared
with smokers.

Lead author Giannis Mountzios, MD,
of the Institut Gustave Roussy, Villejuif,
France, reported the findings at the 31st
Congress of the European Society for
Medical Oncology (ESMO) (Late Breaking
Abstract 7).

"We chose this type cancer because
we know from large epidemiological
studies that a significant proportion of
nonsmokers, and especially women, develop
it," Dr. Mountzios said. "We
wanted to determine if there was a specific
molecular profile that differentiates
the development of lung adenocarcinoma
in people who have never smoked."

He and his colleagues focused on immunohistochemical
evaluation of several
key downstream mediators of cytoplasmic
and nuclear signaling transduction differthat
are known to be associated with lung
oncogenesis. Using microarray technology
on previously collected tissue samples
from 188 chemonaive patients with
operable lung adenocarcinoma, they assessed
expression of P38, JNK, ERK
(extracellular signal-regulated kinase),
STAT3 (signal transducer and activator
of transcription 3), PKB (protein kinase
B, or AKT), and the DNA-repair gene
ERCC1 (excision repair complement
complex one). The researchers recorded
expression levels in smokers vs neversmokers;
the prognostic value of each
marker was evaluated by correlating
expression profiles with corresponding
clinical parameters.

Strong P38, JNK Overexpression
The team, supervised by Jean Charles
Soria, MD, PhD, and Pierre Fouret, MD,
PhD
, from the Departments of Medicine
and Translational Research, respectively,
at Institut Gustave Roussy, found that
never-smokers vs smokers had significant
overexpression of P38 (P < .001)
and JNK (P = .012), "and, for P38 in
particular, this difference was significant
independent of clinical
parameters known to affect the expression
of these molecules," Dr.
Mountzios said. Expression of P38
in never-smokers was 10-fold
higher than in smokers with lung
adenocarcinoma.

In univariate (but not multivariate)
analyses, P38 and STAT3
expression levels were predictive
of overall survival. In addition,
there was some indication that
ERK expression might be an independent
predictor of disease-free
survival in patients with lung
adenocarcinoma.

"These results suggest that lung
adenocarcinoma may be a different disease in molecular terms in
smokers and nonsmokers," Dr.
Mountzios said.

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