Mutations and protein expression of KIT and PDGFRA genes in ipsilateral testicular seminomas: an immunohistochemical and molecular genetic study

Protein expression and gene mutational status of KIT and PDGFRA were investigated in formalin-fixed, paraffin-embedded specimens of 14 ipsilateral testicular seminomas. The analysis was performed by ordinary immunohistochemistry and polymerase chain reaction-direct sequencing methods. The genetic analysis was performed in exons 9, 11, 13, and 17 of KIT gene and in exons 12 and 18 of PDGFRA gene. Six point mutations of 5 types of KIT gene were recognized in 5 (36%) cases; exon 17 around codon 816 was a hotspot. The mutation sites of KIT gene were as follows: codon 557 in exon 11 (1 case), codon 816 in exon 17 (3 cases), codon 820 in exon 17 (1 case), and codon 822 in exon 17 (1 case). One patient showed multiple mutations of KIT gene. Immunoreactive KIT was recognized in 13 (93%) cases; the expression was strong in the 5 KIT mutation-positive cases, but variable or none in the 9 KIT mutation-negative cases. No PDGFRA gene mutations were observed in all the 14 cases. PDGFRA protein expression was weakly recognized in 12 cases but none in the remaining 2 cases. These data suggest, in testicular seminomas, that 36% of ipsilateral testicular seminomas have KIT mutations, KIT mutations are frequent around codon 816 of exon 17, multiple KIT mutations may be present, KIT expression is stronger in KIT mutation-positive cases than negative cases, PDGFRA gene mutations are absent, and PDGFRA protein is weakly expressed.