Proliferation markers in neuroendocrine tumors: useful or useless? A critical reappraisal

Over the past several years, proliferation markers such as MIB-1 have become important adjuncts in the analysis of neuroendocrine (NE) tumors. Published data have suggested that MIB-1 analysis is useful for the distinction of benign and malignant NE tumors and that it can be used to predict aggressiveness of malignant NE tumors. Analysis of MIB-1, however, is subject to many variables including factors inherent in the basic biology of the tumors, case selection criteria and methods of evaluation of stained sections. While studies of MIB-1 have provided the first step in assessing the malignancy of NE tumors, multiparametric approaches examining the full range of cyclins, cyclin inhibitors, factors controlling apoptosis, oncogenes and tumor suppressor genes will be essential to resolve these issues. For the present. MIB-1, by itself, cannot be used to judge the malignancy of individual NE tumors, but this marker may have utility in identifying subsets of tumors that may have an aggressive course.