精巣腫瘍特異的遺伝子のPCRを用いた分子生物学的診断

Abstract

精巣胚細胞腫におけるmelanoma antigen(MAGE)1-3及びWT1遺伝子mRNAの発現を調べた.MAGE1-3はseminomaで高率に発現を認める傾向にあったが, stageとは相関を示さなかった.一方, WT1は組織型とは相関を示さなかったが, 進行症例で高発現する傾向を示した

Most testicular germ cell tumors have serological tumor markers such as alpha-fetoprotein (AFP) and human chorionic gonadotropin beta-subunit (beta-HCG). On the other hand, molecular staging of these tumors has not been well established compared to other urogenital malignancies like prostate cancer. Recently, melanoma antigen (MAGE) which is one of the tumor-associated antigens recognized by cytotoxic T lymphocytes (CTL) has been found to be present in a variety of malignant tumor types and normal testis. In addition, Wilms' tumor-associated gene WT1 has been found to be expressed in some testicular cancers. Thus, we examined the expression of these genes in testicular cancer tissues and peripheral blood of cancer-bearing patients using reverse transcription-polymerase chain reaction (RT-PCR). The expression of the MAGE1-3 genes was examined in 34 testicular germ cell tumors (24 seminomas and 10 nonseminomas). Of the seminomas and nonseminomas, 87.5% and 40% were positive for MAGE1, 91.7% and 60% for MAGE2, and 83.3% and 30% for MAGE3, respectively. The expression of the MAGE genes was not correlated with the tumor stage. The expression of the WT1 gene was quantified in 26 testicular germ cell tumors. WT1 was highly expressed in 5 of the 7 high stage cases, but in only 4 of the 19 low stage cases (p < 0.01). The mRNA of these genes could not be detected from the peripheral blood of patients with high stage tumors. These results suggest that MAGE genes may be useful tumor markers for molecular staging of testicular cancer, especially seminoma, and that the WT1 gene may be a tumor marker for high stage testicular germ cell tumors. However, these genes cannot yet be used for molecular staging of testicular germ cell tumors.