Relationship between EGFR expression, copy number and mutation in lung adenocarcinomas.
BACKGROUND
This study was designed to investigate EGFR protein expression, EGFR copy number and EGFR mutations in lung adenocarcinomas, to explore the relationship of the three markers.


METHODS
EGFR status was analyzed in surgically resected lung adenocarcinoma samples from 133 Chinese patients by three methods: protein expression (n=133) by standardized immunohistochemistry (IHC), gene copy number (n=133) by fluorescence in situ hybridization (FISH), and mutation analysis using the Scorpion amplification refractory mutation system (ARMS) (n=133).


RESULTS
The results showed that 68.4% of the samples were positive by IHC, 42.1% were positive by FISH, and 63.9% contained activating kinase domain mutations. EGFR mutations were more frequent in non-smoking patients (p=0.008), and EGFR mutations were associated with EGFR FISH positivity (p<0.0001). When using 10% positivity and 2+ as cutoffs, EGFR protein expression was significantly correlated with EGFR FISH positivity (p=0.012) and EGFR mutations (p=0.008) after Bonferroni correction.


CONCLUSIONS
EGFR protein expression, EGFR copy number and EGFR mutations were closely related to each other. Standard methods and interpretation criteria need to be established.
Liang
Zhiyong
Z
Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijng 100730, China.
Zhang
Jing
J
Zeng
Xuan
X
Gao
Jie
J
Wu
Shafei
S
Liu
Tonghua
T
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism* / Q000556:secondary; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D018628:Gene Dosage; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate
C512478:EGFR protein, human; D066246:ErbB Receptors