Epidermal growth factor receptor expression status in lung cancer correlates with its mutation.
The molecular mechanisms for frequent epidermal growth factor receptor (EGFR, a tyrosine kinase [TK]) and HER2 (the preferred coreceptor of EGFR) overexpression in lung cancer are poorly understood. Recent studies have shown the mutations of the TK domain in EGFR and HER2 to be present in lung cancer. The purpose of this study was to investigate the relationship between mutation status and expression of EGFR and HER2 in lung cancer. Immunostaining took place for EGFR and HER2, and mutational analyses for EGFR, HER2, and KRAS (a signaling protein) were conducted using 130 resected lung cancer specimens. Thirty-seven EGFR mutations (28%) and 8 HER2 mutations (6%), both of the TK domains, and 5 KRAS (4%) mutations were found, whereas 73 (56%) EGFR and 47 (36%) HER2 overexpressions were found. EGFR overexpression was seen more frequently in tumors with EGFR mutation (28/37, 76%) than in tumors without EGFR mutations (45/93, 48%; P = .0059). No correlation was found between HER2 mutation and HER2 expression. Multivariate regression revealed that EGFR mutation, adenocarcinoma histology, and HER2 expression were associated with EGFR expression, whereas female sex, EGFR mutation, and EGFR expression were associated with HER2 expression. In conclusion, EGFR and HER2 overexpression is frequent in lung cancer, and EGFR overexpression correlates with the EGFR TK domain mutations.
Suzuki
Makoto
M
Department of Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
Shigematsu
Hisayuki
H
Hiroshima
Kenzo
K
Iizasa
Toshihiko
T
Nakatani
Yukio
Y
Minna
John D
JD
Gazdar
Adi F
AF
Fujisawa
Takehiko
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D020440:Gene Duplication; D006801:Humans; D007150:Immunohistochemistry; D007564:Japan; D008175:Lung Neoplasms / Q000145:classification / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016254:Mutagenesis, Insertional; D009154:Mutation; D009367:Neoplasm Staging; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D012044:Regression Analysis; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D018631:ras Proteins
D004273:DNA, Neoplasm; D066246:ErbB Receptors; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018719:Erb-b2 Receptor Tyrosine Kinases; D018631:ras Proteins; C117307:KRAS protein, human