Immunodetection of proliferating cell nuclear antigen assesses the growth fraction and predicts malignancy in endocrine tumors of the pancreas.

Thirty-five endocrine tumors of the pancreas, 17 functioning and 18 nonfunctioning, were immunohistochemically studied for the expression of proliferating cell nuclear antigen (PCNA) using 19A2 and PC10 monoclonal antibodies. The proportion of PCNA-reactive cells (PCNA index) ranged from 0.2 to 27% in functioning tumors and from 0.1% to 55% in nonfunctioning tumors. PCNA index showed a statistically significant correlation with mitotic and Ki67 indexes. The median values of PCNA index identified three groups of patients: group A (PCNA < or = 2%), including 13 functioning and six nonfunctioning tumors; group B (PCNA between 2 and 5%), including three functioning and three nonfunctioning tumors; group C (PCNA > 5%), including one functioning and nine nonfunctioning tumors. All group A tumors were confined to the pancreas. In group B, the functioning tumors were limited to the pancreas, and the nonfunctioning tumors extended to extrapancreatic tissues. All group C patients had extrapancreatic extension of the disease. At follow-up, a PCNA index higher than 5% correlated to a decreased mean survival. Our data suggest that PCNA index is a reliable tool to assess the growth fraction, discern local from advanced diseases, and predict malignancy in pancreatic endocrine tumors.

Natural killer cell activity in patients with neuroendocrine tumours of the gastrointestinal tract; relation with circulating gastrointestinal hormones.

We have evaluated the peripheral blood natural killer (NK) cell activity and the in vitro effect of recombinant gamma-interferon (r gamma-IFN) on NK cell activity in 23 patients with a neuroendocrine tumour of the pancreas, small intestine or liver, and 23 healthy controls. Patients with a gastrinoma showed a NK cell activity which was not different from that of the control group, whereas patients with another type of neuroendocrine tumour had a decreased NK cell activity compared to the controls (p less than 0.05) and the gastrinoma patients (p less than 0.02). The impaired NK cell activity in these patients was as such not related to the presence of liver metastasis or performance status of the patients. r gamma-IFN significantly stimulated the NK cell activity in patients and controls. However, the cytotoxic response of the patients with a hormone production other than gastrin remained lower than in the two other groups. Follow-up studies in 8 patients showed NK cell activities not to vary with stable disease, to decrease with progressive disease, and to increase with regression of disease. In conclusion, NK cell activity is suppressed in patients with neuroendocrine tumours that produce hormones other than gastrin. This impairment is not related to the presence of metastasis but seems to be related to the course of the disease.

Suppressed colony formation of peripheral blood lymphocytes in a patient with somatostatinoma.

The in vitro clonal growth of T lymphocytes was examined in a patient with somatostatinoma over a period of 8 months. After phytohemagglutinin stimulation colony-forming unit T lymphocytes could not be detected as compared to healthy controls and patients with metastatic colon tumors. The somatostatin produced by this tumor was identified as somatostatin-14. Synthetic somatostatin-14 inhibits significantly the colony formation and the tritiated thymidine incorporation of human peripheral T lymphocytes obtained from healthy subjects, suggesting immunoregulative properties of this neuroendocrine peptide.

Duodenal somatostatinoma. Immunohistopathology and review of literature.

A case of duodenal somatostatinoma is reported. The patient, a 54-year-old male, had complained of an epigastric pain due to gastric ulcer and a duodenal polyp was unexpectedly found at a gastrectomy. The polyp showed basically tubular adenocarcinoma, with negative argyrophil and argentaffin reactions. By an indirect immunofluorescent examination almost all of the tumor cells were revealed as somatostatin-immunoreactive. Big somatostatin was also positive. Radioimmunoassay of the tumor indicated 6400 pg of somatostatin-like immunoreactivity per milligram of wet tissue. This seems to be the second case of duodenal somatostatinoma, following the case reported by us previously.