STEM-CELL FACTOR AND ITS RECEPTOR C-KIT - IMPACT ON GERM-CELL MATURATION AND THE DEVELOPMENT OF TESTICULAR GERM-CELL TUMORS

Impact on Germ Cell Maturation and the Development of Testicular Germ Cell Tumors: Stem cell factor (SCF), a hematopoietic growth factor, ha s been identified as the natural ligand of the tyrosine-kinase recepto r, encoded by the c-kit protooncogene. The receptor-ligand complex for med by SCF and c-Kit seems to play a fundamental role in the early dev elopment of testicular germ cells. In a small number of human malignan cies such as brast cancer, small cell lung cancer and testicular germ cell tumors, altered c-Kit expression has been identified. The gene se quence encoding for the stem cell factor has been mapped to chromosome #12q22. For about 80% of testicular germ cell tumors the formation of isochromosome i(12 p) has been described. Additionally, in testicular germ cell tumors, allelic deletion of #12q13 and #12q22 is a frequent ly occurring genetic event, thus suggesting the presence of two putati ve tumor suppressor genes localized at #12q. These genetic alterations might possibly involve the SCF-gene locus. Recent studies suggest tha t altered expression of c-Kit and SCF might participate in the develop ment of testicular germ cell tumors. In the present study the expressi on of c-Kit and SCF in 67 testicular germ cell tumors (42 non-seminoma tous tumors and 25 seminomas) was investigated by an immunohistochemic al approach (APAAP-technique). In 12 additional cases normal testicula r tissue was incubated with monoclonal antibodies for c-Kit and SCF. I n all cases coexpression of c-Kit and SCF could be observed. In the ge rm cell tumors a distinct correlation between the immunohistochemical reaction for c-Kit and SCF was observed. Of 25 (93%) seminomas, 23 exh ibited a positive staining reaction for both c-Kit and SCF. In contras t, in 8 of 40 (20%) cases, embryonal carcinomas as well as the epithel ial areas with cellular differentiation representing embryonal cells r eacted with anti-c-Kit and-SCF antibodies. A correlation between the i mmunohistochemical detection of c-Kit and SCF and the clinical stage o f the patients could not be detected. The study presented here indicat es deregulation of autocrine regulatory mechanisms in testicular germ cell tumors compared to expression fo c-Kit and SCF in normal testicul ar tissue and a possible involvement in the pathogenesis of these mali gnancies.