Usefulness of tissue microarrays for assessment of protein expression, gene copy number and mutational status of EGFR in lung adenocarcinoma

被引:38
|
作者
Ilie, Marius I. [1 ,2 ,3 ]
Hofman, Veronique [1 ,2 ,3 ]
Bonnetaud, Christelle [3 ]
Havet, Katia [1 ]
Lespinet-Fabre, Virginie [3 ]
Coelle, Celine [3 ]
Gavric-Tanga, Virginie [3 ]
Venissac, Nicolas [2 ,4 ]
Mouroux, Jerome [2 ,4 ]
Hofman, Paul [1 ,2 ,3 ]
机构
[1] Louis Pasteur Hosp, Lab Clin & Expt Pathol, F-06002 Nice 01, France
[2] Univ Nice Sophia Antipolis, Fac Med, INSERM ERI 21, EA 4319, Nice, France
[3] Louis Pasteur Hosp, CRB INSERM, Human Tissue Biobank Unit, F-06002 Nice 01, France
[4] Louis Pasteur Hosp, Dept Thorac Surg, F-06002 Nice 01, France
关键词
EGFR; Lung adenocarcinoma; Tissue microarrays; Immunohistochemistry; FISH; Sequencing; GROWTH-FACTOR-RECEPTOR; SQUAMOUS-CELL CARCINOMA; IN-SITU-HYBRIDIZATION; TYROSINE KINASE INHIBITORS; PULMONARY ADENOCARCINOMA; GEFITINIB SENSITIVITY; TUMOR-TISSUE; CANCER; AMPLIFICATION; SURVIVAL;
D O I
10.1007/s00428-010-0963-z
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Specific inhibitors targeting the epidermal growth factor receptor (EGFR) can increase survival rates in certain lung adenocarcinoma patients with mutations in the EGFR gene. Although such EGFR-targeted therapies have been approved for use, there is no general consensus among surgical pathologists on how the EGFR status should be tested in lung adenocarcinoma tissues and whether the results of immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and mutational analysis by molecular methods correlate. We evaluated the EGFR status in 61 lung adenocarcinomas by IHC (using total and mutant-specific antibodies against EGFR), by FISH analysis on tissue microarrays (TMAs), and by direct sequencing. The results of each method were compared using chi (2) and kappa appa statistics. The sensitivity and negative predictive value estimating the presence of abnormal EGFR for each test was calculated. The results show that, with respect to expression patterns and clinicopathological parameters, the total and mutant-specific EGFR detected by immunohistochemistry and FISH analysis on TMAs are valid and are equivalent to conventional methods performed on whole-tissue sections. Abnormal EGFR was detected in 52.4% of patients by IHC, FISH, and sequencing. The best sensitivity (100%) and negative predictive value (100%) was determined by evaluating the EGFR status with all methods. Testing for molecular changes in EGFR using a single test is likely to underestimate the presence of EGFR abnormalities. Taken together, these results demonstrate the high potential of TMAs to test for the major mechanisms of EGFR activation in patients with lung adenocarcinoma.
引用
收藏
页码:483 / 495
页数:13
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