CORRELATION BETWEEN SUCCESSFUL HETEROTRANSPLANTATION OF LUNG-TUMORS IN NUDE-MICE, POOR-PROGNOSIS OF PATIENTS AND EXPRESSION OF FOS, JUN, ERBB1, AND RAS

In order to examine whether the expression of the oncoproteins might b e important for the malignancy of tumors, the relationship between the take rate of 88 human squamous cell lung carcinomas in nude mice and the expression of protooncogene products was analyzed. The expression of c-fos, c-jun, c-ras, c-erbB1, c-neu and c-myc at the protein level was investigated by immunohistochemistry. Tumor take was assumed if wi thin three months gr owing nodules were detected and confirmed histolo gically. The take rate of squamous cell lung carcinomas in nude mice w as 49%. Sixty-eight percent of the tumors were positive for Fos, 40% f or Jun, 67% for Ras, 77% for ErbB1, 35 % for Neu and 39% for Myc. Tumo rs with an (over)expression of the proteins encoded by the oncogenes c -fos, c-jun, c-erbB1 and c-ms had a significantly higher take rate in nude mice than tumors without an (over)expression of the oncogene prod ucts. In contrast, the expression of the c-neu and the c-myc genes at the protein level had no influence on the take rate of the tumors in n ude mice. Interestingly, only patients with tumors with an (over)expre ssion of the proteins encoded by the oncogenes c-fos, c-jun, c-erbB1 a nd c-ras had significantly shorter survival times than patients whose tumors did not show an (over) expression of the oncogene products. The se results demonstrate that the aggressiveness of the tumors visible i n the higher take rate of the tumors in nude mice and in the shorter s urvival times of patients can be detected by measurement of the expres sion of c-fos, c-jun, c-erbB1 and c-ras at the protein level.