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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.
Patients And 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.
Insights
KIT and epidermal growth factor receptor (EGFR) are expressed in many refractory germ-cell tumors (GCTs). Further clinical trials will clarify the significance of these findings for incurable GCT patients.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Most germ-cell tumors (GCTs) are curable with standard treatments.
- Molecular distinctions between curable and incurable GCTs remain unclear.
- Investigating KIT and epidermal growth factor receptor (EGFR) expression in refractory GCTs.
Purpose of the Study:
- To determine the incidence of KIT and EGFR expression in chemorefractory GCTs.
- To explore potential molecular targets in treatment-resistant GCTs.
Main Methods:
- Retrospective analysis of 23 patients with chemorefractory non-seminomatous GCTs.
- Immunohistochemical analysis for KIT and EGFR expression.
- Screening for KIT exon 17 mutations using DHPLC and sequencing.
Main Results:
- KIT expression observed in 48% of patients (11/23).
- No activating KIT mutations in exon 17 were detected.
- EGFR expression found in 65% of patients (15/23).
Conclusions:
- KIT and EGFR are expressed in a substantial fraction of refractory GCTs.
- These findings highlight potential therapeutic avenues for GCTs.
- The clinical relevance of KIT and EGFR expression is under investigation in ongoing trials.
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