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Updated: Jul 1, 2026
Analysis of the c-KIT Ligand Promoter Using Chromatin Immunoprecipitation
Published on: June 27, 2017
Analysis of c-kit protein expression in small-cell lung carcinoma and its implication for prognosis
Mohtashim Naeem1, Madhu Dahiya, Joseph I Clark
1Loyola University Medical Center, Maywood, IL, USA.
Abstract:
Recently, therapies targeting signaling pathways involved in the pathogenesis of different tumors have been developed. Studies have shown that the tyrosine kinase inhibitor STI-571 (Gleevec) is used successfully against tumors expressing the c-kit oncogene, such as gastrointestinal stromal tumors (GISTs). A recent in vitro study also demonstrated an antiproliferative effect of STI-571 on small-cell lung cancer (SCLC) cell lines. To determine the expression of c-kit in SCLC, we retrospectively analyzed presence of c-kit by immunohistochemistry in biopsy samples from patients with SCLCs. Formalin-fixed, paraffin-embedded archival tissue samples from 30 SCLCs were stained with an antibody directed against c-kit (CD117) by immunohistochemistry. Thirty cases of SCLCs, including 17 males (age 44 to 89) and 13 females (age 21 to 85), were examined. Sixteen of 30 (53.3%) SCLCs showed c-kit expression. Kaplan-Meier survival analysis with a log-rank test revealed that patients with c-kit expression had a tendency toward lower survival than c-kit-negative patients (median survival, 6 months versus 31 months, P =.062). Based on previously established anti-c-kit effects of STI-571 on SCLC cell lines and our findings, clinical trials may be considered for selected SCLC patients with c-kit expression. Furthermore, determination of c-kit in SCLC may have a prognostic value in SCLC patients.
Insights
This study found that over half of small-cell lung cancer (SCLC) patients express c-kit. C-kit expression in SCLC may indicate a poorer prognosis, suggesting potential targeted therapy with STI-571.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Targeted therapies are emerging for various cancers.
- Tyrosine kinase inhibitors like STI-571 (Gleevec) are effective against c-kit-expressing tumors, such as gastrointestinal stromal tumors (GISTs).
- Pre-clinical studies indicate STI-571 has anti-proliferative effects on small-cell lung cancer (SCLC) cell lines.
Purpose of the Study:
- To investigate the expression of the c-kit oncogene in small-cell lung cancer (SCLC) patient samples.
- To evaluate the potential prognostic value of c-kit expression in SCLC.
- To explore the rationale for clinical trials of STI-571 in SCLC patients with c-kit expression.
Main Methods:
- Retrospective analysis of 30 formalin-fixed, paraffin-embedded SCLC biopsy samples.
- Immunohistochemistry staining using an antibody against c-kit (CD117).
- Kaplan-Meier survival analysis with log-rank testing to assess survival differences based on c-kit expression.
Main Results:
- C-kit expression was detected in 16 out of 30 (53.3%) SCLC cases.
- Patients with c-kit expressing SCLC showed a trend towards lower survival rates compared to c-kit negative patients (median survival: 6 months vs. 31 months, P = 0.062).
- The findings suggest a potential link between c-kit expression and prognosis in SCLC.
Conclusions:
- C-kit is expressed in a significant proportion of small-cell lung cancer cases.
- C-kit expression in SCLC may serve as a prognostic marker, potentially indicating a less favorable outcome.
- The results support further investigation into c-kit targeted therapies, such as STI-571, for selected SCLC patients.
