The Relationship Among Histological Subtypes, Prognosis And EGFR Mutation In Lung Adenocarcinoma

Objective:To investigate the relationship among histological subtypes, EGFR mutation and prognosis of lung adenocarcinoma.Methods:1. All cases of lung adenocacinoma were collected from the archives of the Department of Pathology, Chinese PLA General Hospital including two series.158cases of BAC were between October1995and August2007, and another282cases of adenocarcinoma between April2005and December2011of which EGFR mutation were detected. All patients’slides were reviewed and reclassificated according to the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Classification of Lung Adenocarcinoma, using comprehensive histological subtyping, recording the percentage, in5%increments,of each histological component.2. EGFR gene mutations of exons18through21were detected by direct DNA sequencing.3. Data were analyzed with Statistical Standard Package Service Solution software (13.0).Results:1. Among158cases of BAC,79cases were female and79cases were male, with an average age of59.7yrs (range:31-84),122(77.2%) cases were non-smokers, and majority of patients were stage I (n=126,79.7%). After reclassification, minimally invasive adenocarcinoma (MIA) was the most common subtype (28.4%), followed by lepidic predominant adenocarcinoma (LPA,24.6%). The time of follow-up was64-206months. The prognosis of each subtype was different. Both AIS and MIA had100%5-year disease-free survival rate and100%5-year overall survival rate. Lepidic, acinar, and papillary had intermediate prognosis with87.5%,73.9%and77.8%5-year overall survival rate respectively. Solid and variants of invasive adenocarcinoma cases had poor prognosis with33.3%,41.7%5-year overall survival rate respectively. Higher stage (P=0.000) and age (tumor P=0.000) were associated with worse disease-free survival.2. Among282cases of lung adenocarcinoma, There were145men and137women aged 20to86years (mean,60.4years). All patients were Chinese. There were198never smokers,48former smokers, and36current smokers. Pathologic stages were stage I in112patients, stage Ⅱ in19patients, and stage Ⅲ in74patients, stage Ⅳ in17patients. Epidermal growth factor receptor mutations were detected in165of a total of282cases (58.5%). Exons with mutations were as follows:of a total of165mutated carcinomas,85(51.5%) were in exon19,9(5.4%) in exon20, and69(41.8%) in exon21. The most common mutation was in-frame deletions in exon19and the second most common mutation was point mutations in exon21. Epidermal growth factor receptor mutations were detected more frequently in women (66.4%) than in men (51.0%), the difference was statistically significant (P=0.009). EGFR mutations were more frequent in never smokers (64.9%) than in former smokers (52.2%) and current smokers (41.5%; P=0.003). Age, tumor size, and pathologic stage did not show significant associations with frequency of EGFR mutations. The most frequent subtype was acinar predominant. Epidermal growth factor receptor mutations were significantly more frequent in the micropapillary predominant subtype (8/10,80%) than in the other subtypes (157/272,57.7%), the second was LPA (78.7%), In contrast, EGFR mutations were less frequent in the solid predominant subtype (32.1%). The histopathologic subtypes correlated with EGFR mutations (P=0.000).Conclusions:1.Discontinuing the use of the term "BAC" is reasonable and important.2The prognosis of each subtype was different. Both AIS and MIA had good prognosis, but Solid and variants of invasive adenocarcinoma had poor prognosis3. The histopathologic subtypes correlated with EGFR mutations, Epidermal growth factor receptor mutations were significantly more frequent in the micropapillary predominant subtype (8/10,80%) than in the other subtypes. Meantime, Epidermal growth factor receptor mutations were detected more frequently in women and never smokers.