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.