EXPRESSION OF C-MYC AND C-RAS ONCOGENES IN THE NEOPLASTIC AND NONNEOPLASTIC CELLS OF HODGKINS-DISEASE

The oncogenes c-myc and c-ras are known to elicit a cooperative tumori genicity. In this study we investigated their role in the pathogenesis of Hodgkin's disease. The expression of these oncogenes was determine d in Hodgkin's disease patients by avidin-biotin peroxidase complex im munohistochemical staining and was compared to their expression in pat ients with non-Hodgkin's lymphomas and inflammatory reactive lymph nod es. Of 29 examined patients with different histological types of Hodgk in's disease, 21 (72.4%) showed an elevated expression of c-myc and 28 (96.5%) of c-ras. Although this expression was marked especially in t he neoplastic Reed-Sternberg cells, it was also noted in the numerous reactive cells present in the involved lymph nodes. By contrast, a muc h lower frequency of increased expression of these oncogenes was recor ded in 19 patients with different grades of non-Hodgkin's lymphoma and in 29 patients with inflammatory reactive lymph nodes. The elevated e xpression of c-myc and c-ras in the neoplastic Reed-Sternberg cells ma y reflect an oncogenic event that directly activates these genes. Howe ver, their increased expression in the surrounding non-neoplastic cell s probably results from signal transduction induced by certain growth- promoting factors possibly released by the Reed-Sternberg cells and th at act paracrinally to stimulate the proliferation of the neighboring cells. Furthermore, the continuous c-ras elevation may impair the norm al cell cycle control and thereby promote mutagenesis and overt malign ancy.