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 comprise a functionally and biologically heterogeneous group of neoplasms that rarely show reliable histopathologic signs of malignancy. No etiologic factors are proven to be associated with them, and their exact ontogeny and carcinogenesis remain unknown.

METHODS

Monoclonal antibodies were employed, along with microwave antigen retrieval and the avidin-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 nuclear antigen (PCNA) in a retrospective series of 116 primary gastroenteropancreatic neuroendocrine tumors (GPNTs). The authors attempted to correlate this expression with the clinicopathologic outcome of the disease.

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 pancreatic neuroendocrine tumors (PNTs), respectively. In carcinoid tumors, immunoreactivities 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 higher incidences of c-myc, bcl-2, and c-erb B-2 immunoreactivities in carcinoid tumors of the rectum than in those of the appendix, and significantly higher incidences of bcl-2 and c-jun immunoreactivities in carcinoid tumors of the bronchus than in those of the appendix. Incidence of PCNA immunoreactivity was significantly higher in malignant than in benign PNTs and also significantly higher in carcinoid tumors of the jejunum and ileum than in those of the appendix.

CONCLUSIONS

The oncogenes c-myc, bcl-2, c-erb B-2, and c-jun are frequently expressed in human GPNTs. The expression of these oncogenes may represent pathogenic events in the generation, malignant transformation, and progression of GPNTs. The immunohistochemical evaluation of cell kinetics in GPNTs by PCNA might be a useful adjunct to conventional diagnostic procedures.