Expression of KIT and epidermal growth factor receptor in chemotherapy refractory non-seminomatous germ-cell tumors.
BACKGROUND
The majority of patients with germ-cell tumors (GCTs) are curable with standard therapy. The molecular differences between curable and incurable disease are unknown. We have studied the expression of KIT and the epidermal growth factor receptor (EGFR) to determine their incidence in chemorefractory disease.


METHODS
We retrospectively analyzed 23 patients with chemorefractory non-seminomatous GCTs (15 late relapse and eight transformed teratomas). None of these 23 patients were cured by their initial chemotherapy and/or surgery. Immunohistochemical analysis of KIT and EGFR was performed on the most recently available specimen from a metastatic site. PCR amplimers of KIT exon 17 were screened for mutations by a combination of denaturing high-performance liquid chromatography and direct sequencing.


RESULTS
KIT was expressed (>/=10% of the tumor displaying membranous or cytoplasmic staining) in 11 of 23 GCT patients [48%; 95% confidence interval (CI) 26% to 68%]. There were no activating KIT mutations in the phosphoryltransferase domain (exon 17) in 21 patients analyzed. EGFR was expressed (1+ to 3+) in 15 of 23 GCT patients (65%; 95% CI 41% to 82%).


CONCLUSIONS
KIT and EGFR are expressed in a significant proportion of refractory GCTs. The significance of these findings will be determined by ongoing clinical trials.
Madani
A
A
Division of Hematology and Oncology, and Department of Pathology, Indiana University Medical Center, Indianapolis, IN 46202, USA. amadani@iupui.edu
Kemmer
K
K
Sweeney
C
C
Corless
C
C
Ulbright
T
T
Heinrich
M
M
Einhorn
L
L
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D017931:DNA Primers / Q000737:chemistry; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000378:metabolism*; D005091:Exons / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D018237:Germinoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D013724:Teratoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D013736:Testicular Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D017931:DNA Primers; D066246:ErbB Receptors; D019009:Proto-Oncogene Proteins c-kit