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Evaluation of c-kit (CD 117) expression as a prognostic factor in testicular germ cell tumors: an Izmir Oncology
Tarik Salman1, Elif Yildiz, Ibrahim Yildiz
1Izmir Katip Celebi University, Ataturk Research and Training Hospital, Department of Medical Oncology, Izmir, Turkey.
Purpose:
Despite the successful use of targeted and molecular therapies in other cancers, little progress has been made in the management of testicular germ cell tumors (TGCTs). c-kit (CD 117) is a good target for cancer treatment and possesses an impressive role in the current oncological practice. We aimed to evaluate c-kit expression in early stage TGCTs as a prognostic factor.
Methods:
Patients with TGCTs who were referred to the Medical Oncology Clinic and underwent curative surgical operation were included in our study before starting chemo- therapy. Immunohistochemistry was performed on formalin-fixed and paraffin-embedded three-micrometer thick sections with CD 117 Rabbit Anti c-kit in vitro gene kit. Biochemically, we utilized AFP and β-HCG Immunlite 2000 device with solid phase chemiluminescent immunometric method, and LDH Roche models with the DP-standardized UV method. AFP 0-15 ng/ml, β-HCG < 0.1 mlu/ml and LDH 240-480 mg/dl were considered as normal values.
Results:
Sixty-five patients were included in our study. Forty-one (63%) patients had non-seminoma tumors (NSGCTs) and 24 (37%) had seminoma. Statistically significant c-kit expression was found in patients with seminoma (p<0.0001). There was no difference between negative or positive c-kit expression in terms of clinicopathological characteristics, including preoperative serum levels of AFP, β-HCG, LDH, lymph node involvement, distant metastasis, and IGCCCG risk classification. No correlation was found between these parameters and 5-year progression free survival (PFS) rate except for tumor stage, presence of lymph node metastasis and IGCCCG score (p=0.001, p=0.04, and p=0.0001, respectively). Five-year PFS rate of patients with positive CD 117 was 72.2% (95% CI, 54.6-89.8), and 56.6% (95% CI, 31.2-82.1) for those without CD 117 expression involvement (p=0.12).
Conclusion:
So far, there has been no significant breakthrough in the treatment of cisplatin-refractory TGCTs in the era of targeted therapies. No prognostic importance of c-kit expression has been found in our study. However, we believe that c-kit expression, in numerical terms, can be considered as a good prognostic factor for patients with TGCTs. The fact that all seminoma cases displayed positive c-kit expression is what we think has driven this result.
Insights
C-kit (CD 117) expression shows potential as a prognostic factor in early-stage testicular germ cell tumors (TGCTs). While not statistically significant in this study, positive c-kit expression correlated with better progression-free survival, especially in seminoma cases.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Targeted and molecular therapies have limited impact on testicular germ cell tumors (TGCTs).
- C-kit (CD 117) is a promising molecular target in oncology.
- Evaluating c-kit expression in early-stage TGCTs is crucial for prognostic assessment.
Purpose of the Study:
- To investigate the role of c-kit (CD 117) expression as a prognostic factor in early-stage TGCTs.
- To assess the correlation between c-kit expression and clinicopathological characteristics.
- To determine the association between c-kit expression and progression-free survival (PFS).
Main Methods:
- Immunohistochemistry was used to evaluate c-kit expression in tumor samples from 65 TGCT patients.
- Serum levels of AFP, β-HCG, and LDH were measured biochemically.
- Clinicopathological data and 5-year PFS rates were analyzed.
Main Results:
- C-kit expression was significantly higher in seminoma (37%) compared to non-seminoma TGCTs (63%) (p<0.0001).
- No significant correlation was found between c-kit expression and clinicopathological factors or IGCCCG risk classification.
- Five-year PFS was 72.2% for patients with positive c-kit expression versus 56.6% for those without (p=0.12).
Conclusions:
- C-kit expression did not demonstrate statistically significant prognostic importance in this cohort.
- A trend suggests c-kit expression may be a favorable prognostic indicator, particularly in seminoma.
- Further research is warranted to elucidate the precise role of c-kit in TGCT management.