ONCOGENE EXPRESSION IN GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS -IMPLICATIONS FOR PATHOGENESIS

BACKGROUND. Neuroendocrine tumors of the gastroenteropancreatic system include pancreatic islet cell and carcinoid tumors. These tumors comp rise a functionally and biologically heterogeneous group of neoplasms that rarely show reliable histopathologic signs of malignancy. No etio logic factors are proven to be associated with them, and their exact o ntogeny and carcinogenesis remain unknown. METHODS. Monoclonal antibod ies were employed, along with microwave antigen retrieval and the avid in-biotin immunohistochemical method, to investigate the expression of c-myc, bcl-2, c-erb B-2, c-erb B-3, c-jun, and proliferating cell nuc lear antigen (PCNA) in a retrospective series of 116 primary gastroent eropancreatic neuroendocrine tumors (GPNTs). The authors attempted to correlate this expression with the clinicopathologic outcome of the di sease. RESULTS. Immunoreactivities for c-myc, bcl-2, c-erb B-2, c-erb B-3, and c-jun were detected in 100%, 45%, 24%, 7%, and 24% of pancrea tic neuroendocrine tumors (PNTs), respectively. In carcinoid tumors, i mmunoreactivities were detected for c-myc (63%), bcl-2 (28%), c-erb B- 2 (31%), c-erb B-3 (6%), and c-jun (23%). There were significantly hig her incidences of c-myc, bcl-2, and c-erb B-2 immunoreactivities in ca rcinoid tumors of the rectum than in those of the appendix, and signif icantly higher incidences of bcl-2 and c-jun immunoreactivities in car cinoid tumors of the bronchus than in those of the appendix. Incidence of PCNA immunoreactivity was significantly higher in malignant than i n benign PNTs and also significantly higher in carcinoid tumors of the jejunum and ileum than in those of the appendix. CONCLUSIONS. The onc ogenes c-myc, bcl-2, c-erb B-2, and c-jun are frequently expressed in human GPNTs. The expression of these oncogenes may represent pathogeni c events in the generation, malignant: transformation, and progression of GPNTs. The immunohistochemical evaluation of cell kinetics in GPNT s by PCNA might be a useful adjunct to conventional diagnostic procedu res. (C) 1997 American Cancer Society.