Correlation between HLA alleles and EGFR mutation in Japanese patients with adenocarcinoma of the lung.
BACKGROUND
The identification of activating mutations in the epidermal growth factor receptor (EGFR) gene is one of the most intriguing recent discoveries in the field of lung cancer research, and they are more commonly found in adenocarcinoma occurring in females, never/light smokers, and East Asian patients. Why such certain patients are susceptible to the development of EGFR-mutant tumors is currently unknown.


METHODS
This study evaluated the medical records of 437 patients with adenocarcinoma of the lung who underwent a surgical resection. The genetic status of the EGFR gene was investigated by polymerase chain reaction-based analyses. The serological typing of histocompatibility leukocyte antigen (HLA) class I was performed using a microcytotoxicity test of lymphocytes or polymerase chain reaction-sequence-specific oligonucleotides, and the correlation between the EGFR mutation and HLA alleles was analyzed.


RESULTS
An EGFR mutation was found more frequently in females and never/former smokers than their counterpart. In females, the incidences of EGFR mutation were 61.0% and 41.7% in HLA-A2 (+) and A2 (-) patients with adenocarcinoma of the lung, respectively (p = 0.008). The EGFR mutation was found more frequently in female patients with HLA-A2. However, no significant correlation was identified between the frequencies of other HLA alleles and EGFR mutations in the same patients group.


CONCLUSIONS
EGFR: mutations are associated with HLA-A2 in female patients with adenocarcinoma of the lung. Further research was needed to elucidate the other relevant factors in the histogenesis of lung cancer with an EGFR mutation.
Uramoto
Hidetaka
H
Second Department of Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. hidetaka@med.uoeh-u.ac.jp
So
Tomoko
T
Nagata
Yoshika
Y
Kuroda
Koji
K
Shigematsu
Yoshiki
Y
Baba
Tetsuro
T
So
Tetsuya
T
Takenoyama
Mitsuhiro
M
Hanagiri
Takeshi
T
Yasumoto
Kosei
K
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D004247:DNA / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006649:Histocompatibility Antigens / Q000235:genetics*; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D015996:Survival Rate; D055815:Young Adult
D006649:Histocompatibility Antigens; D004247:DNA; C512478:EGFR protein, human; D066246:ErbB Receptors