EXPRESSION OF THE C-MYC PROTO-ONCOGENE AND THE METASTASIS SUPPRESSOR GENE NM 23 IN TESTICULAR TUMORS. B. Schmidt, R. Ackermann and T. Strohmeyer The c-myc proto-oncogene is involved in the regulation of cellular differentiation and proliferation. Its altered expression, caused by chromosomal translocation, amplification or retroviral insertion is associated with tumor igenes i s in different tumor species. In previous immunohistochemical studies the c-myc oncoprotein was found to be overexpressed only in the serninoma subtype of testicular germ cell tumors (GCT), while low levels were detected in non-serninomas and normal testicular tissues (Br.J.Cancer 52, 171,1985). The nm 23 protein p17 acts as a metastasis supressorgene in animal models as well as in human breast cancer and has recently been shown to be a putative c-myc transcription factor. In this study the c-myc and nm 23 genes were examined by immunohistochemistry, Northern blotting, restriction fragment length polymorphism (RI=LP) and semiquantitative RT-PCR in testicular GCT of different histology. None of the 8 seminomas and only one of the 13 non-seminomas investigated showed c-myc overexpression in Northern and RT-PCR analyses. No abnormalities of the c-myc were detectex~ at the DNA level. For the nm 23 gene a 2-4 fold IrLRNA overexpression was found in 15/24 (62.5 %) of the tumors. 2/24 (8.3 %) of the tumors showex] a 2 fold lower expression as the compared normal tissue. However, these 2 tumors were without metastases. When studying the Bgl II RFLP 12/19 (63 %) tumors were informative. Out of these, allelic losses of the nm 23 gene were found in only 3/12 (25 %) tumors. One of these had metastasized, however, no statistically significant correlation of these findings with tumor stage was found. In conclusion, c-myc seems to be of no value as a single prognostic factor in in human GCT. Inactivation of nm 23 due to allelic loss seems to ~ a rare event and doesn't correlate in these few tumors with metastases. However, nm 23 mutations undetectable by Ra~LP analysis could be responsible for the overexpression of the gene found in the majority of the GCT. Therefore, studies on a larger cohort of GCT including mutational analyses of both nm 23 genes and immunohistochernistry seem to clarify this problem. Although the nm 23 protein has been shown to be the c-myc transcription factor PuF, no co-expression of these genes has been found in this tumor system until now.