title: Evaluation of c-kit (CD 117) expression as a prognostic factor in testicular germ cell tumors: an Izmir Oncology Group (IZOG) study.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Izmir Katip Celebi University, Ataturk Research and Training Hospital, Department of Medical Oncology, Izmir, Turkey.
authors.forename: Tarik
authors.initials: T
authors.lastname: Salman
authors.forename: Elif
authors.initials: E
authors.lastname: Yildiz
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Yildiz
authors.forename: Dilek
authors.initials: D
authors.lastname: Yavuzer
authors.forename: Mehtat
authors.initials: M
authors.lastname: Unlu
authors.forename: Umut
authors.initials: U
authors.lastname: Varol
authors.forename: Murat
authors.initials: M
authors.lastname: Akyol
authors.forename: Yasar
authors.initials: Y
authors.lastname: Yildiz
authors.forename: Vedat
authors.initials: V
authors.lastname: Bayoglu
authors.forename: Yksel
authors.initials: Y
authors.lastname: Kucukzeybek
authors.forename: Ahmet
authors.initials: A
authors.lastname: Alacacioglu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000737:chemistry / Q000401:mortality*; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis*; D013736:Testicular Neoplasms / Q000737:chemistry / Q000401:mortality*
chemical_list: D019009:Proto-Oncogene Proteins c-kit