Expression of c-myc and c-ras oncogenes in the neoplastic and non-neoplastic cells of Hodgkin's disease.
The oncogenes c-myc and c-ras are known to elicit a cooperative tumorigenicity. In this study we investigated their role in the pathogenesis of Hodgkin's disease. The expression of these oncogenes was determined in Hodgkin's disease patients by avidin-biotin peroxidase complex immunohistochemical staining and was compared to their expression in patients with non-Hodgkin's lymphomas and inflammatory reactive lymph nodes. Of 29 examined patients with different histological types of Hodgkin'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 the neoplastic Reed-Sternberg cells, it was also noted in the numerous reactive cells present in the involved lymph nodes. By contrast, a much lower frequency of increased expression of these oncogenes was recorded in 19 patients with different grades of non-Hodgkin's lymphoma and in 29 patients with inflammatory reactive lymph nodes. The elevated expression of c-myc and c-ras in the neoplastic Reed-Sternberg cells may reflect an oncogenic event that directly activates these genes. However, their increased expression in the surrounding non-neoplastic cells probably results from signal transduction induced by certain growth-promoting factors possibly released by the Reed-Sternberg cells and that act paracrinally to stimulate the proliferation of the neighboring cells. Furthermore, the continuous c-ras elevation may impair the normal cell cycle control and thereby promote mutagenesis and overt malignancy.
Benharroch
D
D
Department of Oncology, Soroka Medical Center of Kupat Holim, Israel.
Yermiahu
T
T
Geffen
D B
DB
Prinsloo
I
I
Gopas
J
J
Segal
S
S
Aboud
M
M
D015870:Gene Expression; D016259:Genes, myc / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D015614:Histiocytosis / Q000235:genetics; D006689:Hodgkin Disease / Q000235:genetics*; D006801:Humans; D006965:Hyperplasia; D007124:Immunoenzyme Techniques; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008199:Lymphadenitis / Q000235:genetics; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics; D016539:Reed-Sternberg Cells / Q000737:chemistry