The Correlation Analysis Between EGFR Gene Mutation And Histologic Subtypes & Clinical Characteristics In Patients With Lung Adenocarcinoma

Background and purpose:Lung cancer is the worldwide first rank of tumor-associated diseases with incidence and mortality. Adenocarcinoma(AC) as the highest incidence type of lung cancer has been widely concerned and in-depth studied. The new classification standard of lung adenocarcinoma which was proposed by International Society for the Study of lung cancer, the American Thoracic Society and European Respiratory Society(IASLC / ATS / ERS) in 2011 divided AC into more specific histological subtypes, and revealed intricate relationship between histological subtype and EGFR mutations in AC. The purpose of this study is in order to provide reliable proof for further exploring the mechanisms of development of AC and molecular targeted therapy, through a retrospective analysis of correlation between histological subtypes and EGFR mutation status and general characteristics in patients who were confirmed to be AC after surgery.Materials and methods:Select 397 cases patients who were diagnosed as lung adenocarcinoma after surgery from January 2008 to June 2013 in our hospital. All clinical data of patients access to previous medical records from the hospital library. Collect the clinical data of patient sex, age, smoking history, tumor location, tumor size, surgical style and clinical stage. Clinical staging was performed referred to 2002 sixth edition TNM staging of lung cancer and 2007 edition TNM staging of lung cancer. Follow-up was performed by telephone, review and patient follow-up way. The patients with postoperative follow-up lost, no accurate clinical staging and perioperative mortality were excluded. Histological subtypes were classified based on 2004 WHO classification and 2011 latest IASLC/ATS/ERS classification method. The expression level of thyroid transcription factor(TTF-1) was detected by immunohistochemistry methods. Liquid chip assay was used to test EGFR mutation status. Analyzed the difference of old and new clinical stage, pathological types of old and new editions and re-distribution of the relevant factors affecting the old and new staging, EGFR mutation status and the relationship with TTF-1, old and new pathological and clinical pathological features, meanwhile analyzed the influence of EGFR mutation status, TTF-1 level as well as all clinical and pathological factors to the prognosis in lung cancer patients. Differences between groups were compared using Fisher’s exact test or χ2 factor test method. Log-Rank analysis methods were applied to compare the patients’ survival in different groups. All data werestatistically analyzed using SPSS 17.0 software, P <0.05 was considered statistically significant.Results:1. In accordance with the seventh edition of the TNM classification, some patients appeared relatively changes on staging in comparison with the sixth edition TNM classification, but the new staging standard for predicting prognosis showed no more significant advantages than old staging standard.2. Of lung adenocarcinoma patients(n = 200), TTF-1 expression rate and EGFR mutation rate were of 81.5% and 45.5%, respectively. In non-smoking female lung cancer patients(N = 72), TTF-1 and EGFR expression showed higher rates(93.1% and 63.9%, respectively). There was a positive correlation(P <0.001) between TTF-1 expression and EGFR mutations, especially TTF-1 expression with the exon 21 mutations, which were significantly associated(P = 0.001). Survival analysis showed that in Ⅲ- Ⅳstage lung cancer patients, both positive of TTF-1 expression and EGFR mutations showed significantly better prognosis than patients with both of TTF-1 expression and EGFR mutations were negative(P = 0.027).3. In terms of survival, the prognosis of patients with EGFR mutant were better than patients with wild-type, but the difference was not statistically significant(P=0.016). Univariate Kaplan-Meier survival analysis showed that in all patients clinicopathologic factors, only stage Ⅰ- was a statistically good prognosis factors Ⅱ(P <0.05).4. In accordance with the IASLC/ATS/ERS new classification criteria in 2011, lepidic predominant has the highest EGFR mutation rate, while rare EGFR mutation has been found in invasive mucinous adenocarcinoma patients.Conclusion:1. Lung adenocarcinoma is a special type of lung cancer, its special histologic subtypes and high mutation rates of EGFR will affect the prognosis. Furthermore, the specific T staging of ALI will also result in changes of prognosis by affecting clinical stages. There are some shortcomings relying solely on clinical stage to predict the prognosis of patients.2. The close relationship between TTF-1 expression and EGFR mutations indicated that TTF-1 is expected to become effective EGFR mutation status prediction molecular biomarker. Especially for the patients with negative expression of TTF-1, should choose chemotherapy as soon as possible.3. EGFR mutant occur in the Lepidic predominant and papillary predominantadenocarcinomas with higher frequencies and the lower incidence in mucinous adenocarcinomas. However, the intrinsic relationship between EGFR mutation status and histological subtypes in adenocarcinomas need further research.4. EGFR tyrosine kinase inhibitors(TKIs) are still the treatment of NSCLC, especially to adenocarcinoma patients with EGFR mutations. Exploring relations of the clinical stage, histologic subtype, and EGFR mutation status and applying the three factors together for diagnosis and treatment of lung cancer, now and in the future will be a fairly long period of time the focus of the medical profession to treat lung cancer.