A Study of Biological Behavior Based on the Expression of a Proliferating Antigen in Neuroendocrine Tumors of the Digestive System

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Abstract
The expression of a proliferating antigen by Ki-67 immunohistochemistry was evaluated in 32 gastrointestinal carcinoids and in 5 pancreatic islet cell tumors. In the tissue sections the number of labelled nuclei was calculated per tumor area. The tumors were classified as low proliferating (less than 0.3 labelled cells/mm2), medium proliferating (0.3-1 labelled cells/mm2), and high proliferating (greater than 1 labelled cell/mm2). In 26 tumors obtained from patients receiving antitumor therapy (alpha-interferon) the proliferative activity was decreased. In treated midgut carcinoids the proliferative activity in metastatic tissue was significantly reduced (p less than 0.05). Though not statistically significant, primary midgut carcinoids collected from untreated patients displayed a lower proliferative activity than liver metastases. A survival analysis revealed that patients with tumors displaying low proliferative activity had a better survival than those with high proliferative activity (p less than 0.05). Single cell cytofluorometric DNA analyses showed regular diploid stem cell lines in the majority of tumors from untreated patients (9/11 cases). No correlation was found between the calculated proliferative activity and the DNA profile. The obtained results indicate that the expression of a proliferation antigen by Ki-67 immunohistochemistry can be used to evaluate the biological behavior of neuroendocrine tumors of the digestive system and predict survival.

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