The Feasibility Of CEA To Indicate EGFR Gene Mutations In Non-small Cell Lung Cancer

Objective:Non-small cell lung cancer (NSCLC) is one of malignant tumors with rising incidence. Although the chemotherapy is the principal postoperative treatment of NSCLC, it always takes huge side effect to patients. Therefore the molecular targeted therapy which is in view of special target spot of molecular is applied clinically. Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase, which plays a crucial role in signal transduction of cell proliferation and differentiation. Inhibition for the activation of EGFR can prohibit the cell proliferation. The epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) as a drug specifically affecting EGFR, is used to treat NSCLC. Unfortunately, only a part of patients were sensitive to EGFR-TKI. Massive clinical observations discovered that women, non-smokers, adenocarcinoma and Asian were sensitive agents to this drug, and the tumor with EGFR gene mutations in 19 and 21 exon was sensitive to the drug. Therefore detection of these mutations becomes a quite accurate method to judge the response of patients to EGFR-TKI. Nevertheless, the detection procedure is too complicated to use extensively, a convenience method to help clinician judge whether the patient is sensitive to the drug has being needed. Carcinoembryonic antigen (CEA) is usually used to reflect the growth, recurrence and metastasis of some kinds of tumors and judge the chemo therapeutic effect of patients. whether CEA could be used as a specific marker of sensitive for patients to EGFR-TKI would need to research.Methods:A total 154 specimens of NSCLC were selected from different hospitals of Dalian. The mutations in exonl9 and 21 of EGFR gene were detected by direct DNA sequencing method. Protein expression of CEA was detected by immunohistochemistry. Experimental data were processed by SPSS 11.5 statistical software.Results:EGFR mutations in 19 and 21 exon were found in 56 tumors. The mutation rate was 36.4%(56/154). The mutation rates were 22.4% (22/90) and 53.1%(34/64) in male and female patients (P<0.05), were 36.4% (32/88) and 36.4%(24/66) in the over and below 60-year-old age group (P>0.05), were 8.51%(4/47),53.1%(51/96)and 9.09%(1/11) in squamous cell carcinoma, adenocarcinoma and other types (P<0.05), were 46.0% (40/87) and 23.9%(16/67) in the high and middle differentiation carcinomas and low differentiation carcinomas (P<0.05), were 25.6%(10/39) and 40.0% (46/115) in groups without metastasis and with metastasis (P>0.05), were 16.9%(10/59) and 48.4%(46/95) in patients of smoking and non-smoking (P<0.05), were 38.3%(51/133) and 23.8%(5/21) in patients withⅠ～ⅡandⅢ～Ⅳstaging (P>0.05).EGFR mutations in exonl9 were found in 22 tumors. The mutation rates were 10.0%(9/90) and 20.3%(13/64) in male and female patients (P>0.05), were 14.8%(13/88) and 13.6%(9/66) in the over and below 60-year-old age group (P>0.05), were 2.13%(1/47),21.9%(21/96) and 0% (0/11) in squamous cell carcinoma, adenocarcinoma and other types (P<0.05), were 20.7%(18/87) and 5.97%(4/67) in the high and middle differentiation carcinomas and low differentiation carcinomas (P<0.05), were 12.8%(5/39) and 14.8%(17/115) in groups without metastasis and with metastasis (P>0.05), were 6.78%(4/59) and 18.9%(18/95) in patients of smoking and non-smoking(P<0.05), were 15.0%(20/133) and 9.52%(2/21) in patients with I～II and III～Ⅳstaging (P<0.05).EGFR mutations in exon21 were found in 34 tumors. The mutation rates were 14.4%(13/90) and 32.8%(21/64) in male and female patients (P<0.05), were 21.6%(19/88) and 22.7%(15/66) in the over and below 60-year-old age group (P>0.05), were 6.38%(3/47),31.3%(30/96) and 9.09%(1/11) in squamous cell carcinoma, adenocarcinoma and other types (P<0.05), were 25.3%(22/87) and 17.9%(12/67) in the high and middle differentiation carcinomas and low differentiation carcinoma (P>0.05), were 12.8%(5/39) and 25.2%(29/115) in groups without metastasis and with metastasis (P>0.05), were 10.2%(6/59) and 29.5%(28/95) in patients of smoking and non-smoking (P<0.05), were 23.3%(31/133) and 14.3%(3/21) in patients with I～II and III～Ⅳstaging (P>0.05).The positive rate of CEA protein expression was 69.5%(107/154), were 64.4%(58/90) and 76.6%(49/64) in male and female patients(P>0.05), were 72.7%(64/88) and 65.2%(43/66) in the over and below 60-year-old age group (P>0.05), were 46.8%(22/47),84.4%(81/96) and 36.4%(4/11) in squamous cell carcinoma, adenocarcinoma and other types (P<0.05), were 71.3%(62/87) and 67.2%(45/67) in the high and middle differentiation carcinomas with low differentiation carcinomas (P>0.05), were 53.8% (21/39) and 74.8%(86/115) in groups without metastasis and with metastasis (P<0.05), were 64.4%(38/59) and 72.6%(69/95) in patients of smoking and non-smoking (P>0.05), were 68.4%(91/133) and 76.2%(16/21) in patients with I～Ⅱand III～Ⅳstaging (P>0.05).The expression of CEA was correlated to the mutation in 19 and/or 21 exon of EGFR gene (P=0.003<0.01, r=0.237).Conclusion:1. EGFR gene mutations in 19 and/or 21 exon occurs mainly in female, non-smokers, adenocarcinoma and high and middle differentiation NSCLC.2. EGFR exon19 mutation occurs easily in high and middle differentiation, I～Ⅱstaging NSCLC and non-smoking patients.3. EGFR exon21 mutation occurs easily in female and non-smoking NSCLC patients.4. The CEA protein expression of NSCLC is higher in adenocarcinoma than other types.5. The NSCLC that CEA protein expression is easier to metastasis.6. EGFR gene mutation in 19 and/or 21 exon of NSCLC may occur in the NSCLC with CEA protein expression, therefore CEA can be a marker of judging sensitivity of the patients with NSCLC to EGFR-TKI.