Differential expression of the c‐kit proto‐oncogene in germ cell tumours

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Abstract
The c‐kit proto‐oncogene product and its ligand stem cell factor play an important role in haematopoiesis, spermatogenesis, and melanogenesis. Using an anti‐c‐kit antiserum raised against a synthetic peptide, we studied the immunohistochemical expression of the c‐kit gene product in 60 germ cell tumours (GCTs) (53 testicular, 7 extragonadal), derived from primary GCTs in 45 cases and metastatic tumours in 15 cases. Twenty‐eight out of 28 seminomas showed c‐kit membranous staining in the majority of cells. A similar pattern of expression was seen in intratubular germ cell neoplasia. Nine out of 29 (32 per cent) non‐seminomas displayed cytoplasmic, but not membranous, c‐kit immunoreactivity in occasional cells. In three mixed GCTs, c‐kit expression was limited to the seminoma component. In normal testis, c‐kit expression was observed in some basal tubular cells, corresponding to undifferentiated spermatogonia. These results suggest a role for c‐kit in the oncogenesis of GCT, where down‐regulation of c‐kit might be a critical step during progression from seminomas to non‐seminomas. Immunohistochemical analysis of c‐kit should be considered as a diagnostic aid for GCT and in particular may be helpful in the identification of certain extragonadal seminomas.