| With serious air pollution, the increasingly number of smokers and the changes in peoples diet today, lung cancer incidence and mortality showed rapid growth year by year in China. Especially in Hebei Province, the mortality of lung cancer rose to 306% in the past 40 years, leapt to the top of various types of cancer mortality and lung cancer has become the most dangerous killer to human health. For a long time, doctors regularly depend on traditional chemotherapy such as combining paclitaxel, vinorelbine or gemcitabine with cisplatin, carboplatin or lobaplatin, and radiotherapy to fight against lung cancer, beside surgical resection. However, the curative effect of traditional radiotherapy and chemotherapy for patients with advanced lung cancer are not ideal, the five year survival rate of patients is only 10%~15%.In recent years, as molecular biology research deepens along with the genetic development, targeted therapy for different tumors gradually becomes preferred choice, especially targeted drugs for epidermal growth factor receptor(EGFR) gene mutation in the treatment of non-small cell lung cancer increased significantly, which nowadays becomes a hot area of research in lung cancer genetic level. Researchers found that EGFR mutation mostly happens on exon 19 and 21, particularly East Asia, non-smokers, women, and adenocarcinoma patients. However, whether EGFR mutations correlate with adenocarcinoma histological subtypes and prognosis is rarely reported. Therefore, this study focuses on the pathological characteristics of EGFR mutations in patients with lung adenocarcinoma, the relationship between various adenocarcinoma subtypes and EGFR mutations, and the effect of EGFR mutation on the prognosis of lung adenocarcinoma.Objectives:To evaluate the correlation of EGFR mutations,clinical pathological features and prognosis in patients with lung adenocarcinoma.Methods : By collecting the data of 633 patients of pathologically confirmed lung adenocarcinoma who did lung surgery and hospitalized in the Fourth Hospital of Hebei Medical University from February 2012 to February 2015, using Scorpions ARMS detection method to do amplification, sequencing and analyze with the paraffin-embedded tissue blocks, the relationship were explored between EGFR gene mutation, he clinical pathological characteristics and prognosis of lung adenocarcinoma.Results:1 The detection of EGFR mutation showed that the positive rate of EGFR mutation in patients with lung adenocarcinoma was 56.9%, mainly in No.19-nucleotide deletion in exon mutation and No.21 exon replacement L858 R point based. The positive rates of EGFR mutation in the various histological subtypes of lung adenocarcinoma were respectively micro-invasive 68.8%, lepidic 77.1%, acinar 60.7%, papillary 61.0%, micro-papillary 81.8%, solid 30.0%, mucinous 22.7%, the subtypes showed statistically significant difference(P<0.01).2 The positive rates of EGFR mutation in women accounted for 71.2%, compared to 42.8% in men; accounted for 38.7% in the smokers, while the rate rose up to 67.2% in the non-smokers(P<0.01). The tumor diameter averaged 2.7±1.4cm(P<0.05).In term of TNM staging, 61.8% of patients in stage Ⅰ had EGFR mutations, 44.0% of patients in stage Ⅱ showed EGFR mutations, 53.8% of patients in stage Ⅲ and 50.0% of patients in stage Ⅳhad EGFR mutations. The data also showed that the positive rates of EGFR mutation in the patients with pleural invasion accounted for 60.5%, compared to 53.3% in those without pleural invasion. There were 52.5% of patients with lymph node metastasis, and 59.2% of the patients without metastasis in the patients who had EGFR mutations. The age of patients who had EGFR mutations averaged 59.2±8.6 years old(P>0.05). No significant differences were found in the above different groups.3 Kaplan-Meier survival statistics showed that one year cumulative survival rate(OS) was 95.3% in patients with EGFR gene mutation, compared to 91.4% in patients without EGFR gene mutation. Log Rank significance test showed that the difference of EGFR mutation on prognosis was statistically significant(P<0.001). One year cumulative survival rates of histological subtypes including micro-invasive, lepidic, acinar, papillary, micro-papillary, solid and mucinous of lung adenocarcinoma accounted for 100%, 97.7%, 94.3%, 96.0%, 72.7%, 88.5%, 90.9% respectively(P<0.01). The OS in women, men, smokers, non-smokers, the patients with tumor diameter less than 3cm, tumor diameter greater than or equal to 3cm, with lymph node metastasis, without lymph node metastasis, patients in stage Ⅰ, patients in stage Ⅱ, Ⅲ, Ⅳ respectively were respectively 95.8%, 91.1%, 90.7%, 95.3%, 96.1%, 90.7%, 89.4%, 95.8%, 96.4%, 96.0%, 86.7%, 77.8%(all P<0.05), indicating that the prognosis of patients with lung adenocarcinoma related to gender, smoking history, tumor size, lymph node metastasis, clinical stage and histological subtype. However age, pleural invasion or not, surgical methods or whether the EGFR-TKI in use had no statistical significant differences(P>0.05). The results showed that the factors above were not related to the prognosis of lung adenocarcinoma. According to the K-M survival curve, the subtypes of adenocarcinoma were divided into three groups,(1) micro-invasive, lepidic adenocarcinoma;(2) acinar, papillary, mucinous adenocarcinoma;(3) micro-papillary, solid adenocarcinoma. The three groups were respectively on the behalf of the low, medium and high risk groups, the indexes entered into the COX multi factor regression analysis model including EGFR mutation, sex, smoking history, tumor diameter, lymph node metastasis and clinical stage. The result shows that the tumor TNM staging(P<0.01), smoking history and the tumor size(P<0.05) were statistically significant.Conclusions:1 EGFR mutation more likely happened in the patients of women, non-smokers, smaller tumor size, early clinical stage and lung adenocarcinoma. And it is more likely happened in the patients with micro-papillary, lepidic, papillary, acinar lung adenocarcinoma. On the contrary, EGFR mutation less appears in the invasive mucinous and the solid adenocarcinoma, and it is not related to the age, lymph node metastasis and the pleural infiltration.2 The one year cumulative survival rate of lung adenocarcinoma patients with EGFR gene mutations is higher than that of the patients without EGFR gene mutations, but it is not an independent prognostic factor of lung cancer prognosis. The patients with lepidic growth based lung adenocarcinoma not only have higher EGFR mutation rate, but also survival rate. The lower incidence of EGFR mutations in the solid components of the lung adenocarcinoma patients correlated with poor prognosis. It is worth mentioning that EGFR mutation rate is higher in the patients with micro-papillary lung adenocarcinoma, but have poor prognosis. That means maybe there are different mutation mechanisms of EGFR mutations in different types of lung adenocarcinoma. |
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