KRAS status and epidermal growth factor receptor expression as determinants for anti-EGFR therapies in salivary gland carcinomas.
Salivary gland carcinomas (SGC) are rare cancers with poor prognosis and limited response to conventional chemotherapy. New strategies based on molecular targeted therapy are needed and the EGFR signaling cascade is considered a possible key pathway for therapeutic molecules. We have analyzed 65 SGC of the main histopathological types for the expression of EGFR and and the mutation status of its downstream effector KRAS. EGFR overexpression (+2, +3) has been identified by immunohistochemistry in 75.4%. KRAS mutation analysis was performed by direct genomic sequencing and revealed a KRAS wildtype in 98.5% except of one adenoid cystic carcinoma with a GGT-GAT transition at codon 12 (Gly12Asp). EGFR overexpression and KRAS wildtype are prerequisites for a successful anti-EGFR therapy. The results of this study plead in favor of further therapeutic trials with EGFR-targeting monoclonal antibodies in SGC.
Institute of Pathology, HELIOS Klinikum Erfurt, Germany. rdahse@erfurt.helios-kliniken.de
Regine
R
Dahse
Oliver
O
Driemel
Stephan
S
Schwarz
Katrin
K
Kromeyer-Hauschild
Alexander
A
Berndt
Hartwig
H
Kosmehl
D000368:Aged; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012468:Salivary Gland Neoplasms / Q000235:genetics / Q000378:metabolism
D009363:Neoplasm Proteins; D066246:ErbB Receptors