Immunohistochemical analysis of phosphorylated epidermal growth factor receptor might provide a surrogate marker of EGFR mutation.
OBJECTIVE
Overexpression of EGFR is found in several malignancies including lung cancers. Recently, EGFR mutation has been shown to correlate with responsiveness to tyrosine kinase inhibitors (TKI). Although antibodies against phophorylated EGFR have been used in vitro, phosphorylated EGFR has yet not been examined well in resected non-small cell lung cancers (NSCLCs).


METHODS
We studied the immunohistochemistry of anti-EGFR and phosphorylated EGFR in 97 resected NSCLCs, examined the relationship with EGFR mutation, and performed quantitative RT-PCR of the EGFR gene in the TaqMan assay.


RESULTS
EGFR mutation was seen in 27% of 97 NSCLCs and 37% of 70 adenocarcinomas. EGFR was stained in 60% of 97 NSCLCs. Phosphorylation of tyrosine 845 (pY845) and 1068 (pY1068) was positive in 49% and 48%, respectively. The observed correlation with EGFR mutation and pY845 or pY1068 was statistically significant (P=0.0001 for pY845, P<0.0001 for pY1068, chi square test), although phospho-EGFR status was not associated with a particular mutation type. pY1068-positive tumors also correlated with female, light smoker, and adenocarcinoma histology, but not with mRNA expression. Moreover, patients with pY1068-positive tumors showed prolonged survival (P=0.0093, log-rank test).


CONCLUSIONS
It is possible that immunohistochemistry of phosphorylated EGFR can substitute for EGFR mutation analysis. Further investigation is necessary to determine whether phospho-EGFR immunohistochemistry predicts response to TKIs and survival benefit.
Endoh
Hideki
H
Department of General Surgical Science, Gunma University School of Medicine, Maebashi 371-8511, Gunma, Japan. hid-end@showa.gunma-u.ac.jp
Ishibashi
Yasunori
Y
Yamaki
Ei
E
Yoshida
Takeshi
T
Yajima
Toshiki
T
Kimura
Hitoshi
H
Kosaka
Takayuki
T
Onozato
Ryoichi
R
Tanaka
Shigebumi
S
Mitsudomi
Tetsuya
T
Kuwano
Hiroyuki
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D000077156:Gefitinib; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010766:Phosphorylation; D011799:Quinazolines / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015415:Biomarkers; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib