ErbB4 expression and mutation in Japanese patients with lung cancer.
BACKGROUND
Much evidence has accumulated that the epidermal growth factor receptor (EGFR) and its family members are strongly implicated in the development and progression of lung cancers. Recently, erbB4 kinase domain mutations were reported in Korean patients with lung cancer. We hypothesized that erbB4 mutations correlate with clinicopathologic features of lung cancers.


METHODS
The presence or absence of erbB4 kinase domain mutations was analyzed by reverse-transcription polymerase chain reaction amplification and direct sequencing in 105 surgically treated non-small-cell lung cancer cases from Nagoya City University Hospital. Sixty-three adenocarcinoma cases were included. The EGFR mutation status for these 105 samples were already reported. We have investigated erbB4 expression status by immunohistochemistry in 40 non-small cell lung cancer cases.


RESULTS
ErbB4 mutation was not found in 105 patients with lung cancer. The EGFR mutation status was significantly correlated with sex (women, 74.2% vs. men, 9.5%; P < 0.0001), smoking status (never-smokers, 68.8% vs. smokers, 11%; P < 0.0001), pathologic subtype (adenocarcinoma, 44.4% vs. non-adenocarcinoma, 4.8%; P < 0.0001), and differentiation status of the lung cancer (well-differentiated, 47.4% vs. others, 14.8%; P = 0.0004). We detected ErbB4 protein positivity in 20 samples. The ErbB4 protein status was not significantly correlated with sex (women, 28.6% vs. men, 54.5%; P = 0.4075), smoking status (never-smokers, 69.4% vs. smokers, 16.9%; P < 0.0001), pathologic subtype (adenocarcinoma, 46.2% vs. nonadenocarcinoma, 51.9%; P > 0.9999), or differentiation status of the lung cancer (well-differentiated, 54.5% vs. others, 48.3%; P > 0.9999).


CONCLUSIONS
Thus, erbB4 mutations are rare in Japanese people with lung cancer and of limited value for molecular-targeted therapy.
Department of Surgery II, Nagoya City University Medical School, Nagoya, Japan. hisasaki@med.nagoya-cu.ac.jp
Hidefumi
H
Sasaki
Katsuhiro
K
Okuda
Osamu
O
Kawano
Katsuhiko
K
Endo
Haruhiro
H
Yukiue
Tomoki
T
Yokoyama
Motoki
M
Yano
Yoshitaka
Y
Fujii
D000230:Adenocarcinoma / Q000235:genetics; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D018450:Disease Progression; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007564:Japan; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic; D011379:Prognosis; D066247:Receptor, ErbB-4
D000970:Antineoplastic Agents; C587689:ERBB4 protein, human; D066246:ErbB Receptors; D066247:Receptor, ErbB-4