Female sex and bronchioloalveolar pathologic subtype predict EGFR mutations in non-small cell lung cancer.
OBJECTIVE
The prevalence of epidermal growth factor receptor (EGFR) mutations in gefitinib-naive lung cancer patients is higher in adenocarcinomas, in women, and in Japanese. To further investigate the prevalence of EGFR mutations in relation to ethnic and geographic factors, we evaluated EGFR mutations in a series of Taiwanese patients with primary lung adenocarcinomas who had never been treated with gefitinib.


METHODS
We retrospectively studied 35 primary lung adenocarcinoma samples for mutations in the tyrosine kinase domain of EGFR; exons 18, 19, and 21 were analyzed by nested polymerase chain reaction and automated sequencing. Clinicopathologic information was obtained from patient records and pathology reports. Correlation between EGFR mutations and patient characteristics, including sex, smoking history, and pathologic subtypes, were evaluated by using the chi(2) test and logistic regression analysis.


RESULTS
Heterozygous EGFR mutations were detected in 17 of 35 patients (48%). Missense mutations in exon 21 (13 of 17 patients, 76%) were the most frequent mutations detected. EGFR mutations were more frequent in women (13 of 18 patients [72%]) than in men (4 of 17 patients [23%]; p = 0.004), more frequent in nonsmokers (14 of 21 patients [66%]) than in current smokers (3 of 14 patients [21%]; p = 0.009), and when any degree of bronchioloalveolar carcinoma (BAC) was present (14 of 21 patients [66%]) compared with pure adenocarcinoma (3 of 14 patients [21%]; p = 0.009). Logistic regression analysis demonstrated that female gender (odds ratio [OR], 10.913; 95% confidence interval [CI], 1.778 to 66.97; p = 0.01) and BAC, including adenocarcinomas with any bronchioloalveolar features (OR, 9.708; 95% CI, 1.464 to 64.393; p = 0.019), were significantly associated with EGFR mutations.


CONCLUSIONS
In our series, female sex and bronchioloalveolar pathologic subtype predicted the presence of EGFR mutations in lung adenocarcinomas, and the high frequency of EGFR mutations supports the hypothesis that genetic backgrounds and/or environmental factors may affect the pathogenesis of certain lung cancers.
Hsieh
Ruey-Kuen
RK
Division of Hematology and Oncology, Department of Internal Medicine, Mackay Memorial Hospital 156, Min-Sheng West Rd, Taipei 104, Taiwan.
Lim
Ken-Hong
KH
Kuo
Hsu-Tah
HT
Tzen
Chin-Yuan
CY
Huang
Ming-Jer
MJ
D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D016009:Chi-Square Distribution; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012307:Risk Factors; D012737:Sex Factors
D066246:ErbB Receptors