Font Size: a A A

Clinical Significance Of EGFR Expression And EGFR Mutation In Non-small Cell Lung Cancers

Posted on:2008-05-09Degree:DoctorType:Dissertation
Country:ChinaCandidate:Z J LiFull Text:PDF
GTID:1104360212997932Subject:Surgery
Abstract/Summary:PDF Full Text Request
The morbility and mortality of lung carcinoma (or bronchopulmonary carcinoma) are increasing year by year in the world wide, The morbility of lung carcinoma is the first killer among the male various carcinomas in developed countries and large and middle city in our country. The male and the female is in the ratio of 3-5 vs l. The female morbility of the disease is quickly developing recent years and the age of patients is mainly over 40 years old.Two factors have been affirmed in etiology of lung carcinoma. The first factor is smoking for long stage and the second, air pollution.There is not any advance in surgery for the disease in recent years and the rate of survival is not increased after operation within 5 years. However, a new break-through has been found in molecular biology of the disease, such as carcinoma genes, inhibit-carcinoma genes and other genes. Recent two years, target treatment have changed the fact by EGFR gene mutation.Lung cancer is divided into two big sorts: Non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC). The former is divided again into squamous cell carcinoma, (SCC), adenocarcinoma (AC) and large cell carcinoma (LCC). The morbility of SCC is about 50% among NSCLC, and more in the male. AC morbility is about 20-30% and relative more in the female. The bronchioloalveolar carcinoma is a subtype of AC, The morbility of LCC is the lowest among lung carcinomas.At presence, surgery is a main way for NSCLC. However, the patients with NSCLC about 80%, has losed surgical opportunity before they is diagnosized affirmatively. The best survival rate within 5 years after operation is about 30-40%, and the results is not satisfying. With the research to lung carcinoma in molecular biological mechanism and carcinoma gene mutation, the target treatment becomes gradually a very important way for lung carcinoma clinically. Epidermal growth factor receptor (EGFR) is a focus of target in NSCLC. There is over-expression of EGFR in majority of NSCLC, Such as, so far as to 80% in SCC, about 50-60% in AC and LCC. Some synthetic agents can block conduction of information by EGFR and then inhibit the growth, other activities and apoptosis of lung carcinoma.The reports of gefitinib (or Iressa) as a tyrosine kinase inhibitor is the most, and it's effective rate is about 20% in late stage of NSCLC. However, the patients with AC from the East of Asia has a better effect than one from Europen and American by tyrosine kinase inhibitor, because the rate of EGFR gene mutation in the former is high than the later about 50-60% vs 10%.EGFR gene mutation is a focus of target treatment, and the gene mutations include 3 types, namely 18, 19 and 21exon, which have some subtypes. This mutation leads to the change of ATP-binding pocket in tyrosine kinase domain of EGFR, and can increase the competition of tyrosine kinase inhibitor against ATP over a hundred-fold.Objective in the research is to understand the incidence and characteristics of EGFR and EGFR gene mutation in JiLin province by a number of cases with NSCLC. Following two parts is designed on the research.一,The expression of EGFR in NSCLCObjective: to understand the expression of EGFR and interrelation with some factors in the specimens.Methods: 171 specimens operated with NSCLC is collected in the First Hospital Ji Lin University from Jan, 2002 to Dec, 2005. The expression of EGFR is determined by immunohistochemitry (IHC).Results: The expression rate of EGFR is 64.3%(110/171) in these specimens. The expression of EGFR and interrelation of multi-factors follow: (1)From histopathology, The expression rate of EGFR is 73.9% (51/69) in SCC, 57.7% (56/97) in AC, 66.7% (2/3) in SAC, 100.0% (1/1) in LCC and 0.0% (0/1) in co, respectively (P>0.05); (2)From sex, the expression rate of EGFR is 64.0% (57/89) in the male and 64.6%(53/82) in the female (P>0.05); (3)From smorking history, the expression rate of EGFR is 66.9% (75/112). in smokers and 59.3% (35/59) in non-smokers, (P>0.05); (4)From age, the expression rate of EGFR is 63.2% (36/56) in≤50 years old, 65.3% (47/72). in≤60 years old, and 64.3%(27/42) in≥61 years old, respectively, (P>0.05); (5)From TNM sort (I-IV stage), the expression rate of EGFR is 61.9% (52/84) in I stage, 66.1% (41/62) in II stage, 69.6% (16/23) in III stage and 50.0% (1/2) in IV stage, respectively (P>0.05); (6)From differentiation (I-IV grade), the expression rate of EGFR is 100% (1/1) in undifferential grade, 63.9% (39/61) in low differential grade, 65.3% (47/42) in middle differential grade and 62.1 (23/37) in high differential grade, respectively (P>0.05).Conclusion. There is an over-expression of EGFR in NSCLC and the over-expression has not any interrelation with histopathology, sex, smoking history, age, TNM and differentiation. 二,The expression of EGFR mutation in NSCLC.Objective: To understand the expression of EGFR mutation and interrelation with some factors in these specimens.Methods: 171 specimens operated with NSCLC is collected in the First Hospital, Ji Lin University from Jan 2002 to Dec, 2005. The expression of EGFR mutation (18-21exon) is determined by PCR.Results. The rate of EGFR mutation is 30.9% (53/171) in these specimens. EGFR mutation of 18 exon is not determined out in the specimens ;EGFR mutation of 19 exon is determined out in 33 specimens , in which there are 15 sub-types of EGFR mutation, the common nucleotide of 19 exon deletion is from 2235 seat (9 specimens) and 2238 seat (18 specimens) to 2249 seat (14 specimens); EGFR mutation of 20 exon of determined out in 1 specimen with two seat mutation, namely A substitution to G in 116 seat and C substitution to A in 138 seat and result in D800 G and D807 E in animo acid in-frame of EGFR; EGFR mutation of 21 exon is determined out in 19 specimens with two seat mutation, namely, T substitution to G in 2573 seat and T substitution to A in 2582 seat and result in L858R (14 specimens), L861Q (4 specimens) and L858R with L861Q (1 specimens) in animo acid in-frame of EGFR. The expression of EGFR mutation and interrelation of multi-factors follow: (1) From histopathology, EGFR mutation take place totally in AC and SAC, in which mutation rate of EGFR is 52.6% (51/97) in AC, in which mutation rate is 100.0%(3/3) in BAC subtype and 66.7% (2/3) in SAC. There are no mutation of EGFR in SCC, LCC and CO. (P<0.01); (2) From sex, the rate of EGFR mutation is 23.6%. (21/89) in the male and 39.0% (32/82) in the female (P<0.05); (3) From smoking history. The rate of EGFR mutation is 24.2% (27/112) in smokers and 44.1% (26/59) in non-smokers. (P<0.01); (4) From age, the rate of EGFR mutation is 29.8% (16/57) in≤50 years old, 29.2% (21/72) in≤60 years old, 38.1 (16/42) in≥61 years old, respectively (P>0.05); (5) From TNM sort (I-IV stage), the rate of EGFR mutation is 33.3% (28/84) in I stage, 32.3% (20/62) in II stage, 21.7% (5/23) in III stage, 0.0% (0/2) in IV stage, respectively (P>0.05); (6) From differentiation (I-IV grade), the rate of EGFR mutation is 0.0% (0/1) in undifferential grade, 29.5% (18/61) in low differential grade, 31.9% (21/72) in middle differential grade and 32.4% (12/37) in high differential grade, respectively (P>0.05).Conclusion: EGFR mutation takes place mainly is AC and SAC, in which the mutation take place highly in BAC. EGFR mutation take place mainly in 19 and 21 exon. The mutation of two seat in 20 exon in 1 specimen is found newly. EGFR mutation exist significantly interrelation with histopathology, sex, and smoking history, and dose not any interrelation with age, TNM sort, and differentiation.
Keywords/Search Tags:EGFR, EGFR gene mutation, Exon, NSCLC
PDF Full Text Request
Related items