Although considered a specific marker for Ewing's sarcoma/peripheral 
neuroectodermal tumour, the MIC2 gene product (CD99) has been immunolocalised in 
a variety of human tumours. The present study evaluated immunohistochemically 
the prevalence of CD99 expression in a series of 68 neuroendocrine tumours of 
different gastrointestinal and pulmonary sites. We now report on membrane and/or 
granular cytoplasmic immunoreactivity in 25% of these tumours, independent of 
their anatomical sites. In lung neuroendocrine tumours, CD99 was preferentially 
confined to typical carcinoids (P=0.009). A statistically significant 
relationship was observed between the number of CD99 positive cells but not the 
immunostaining patterns and the presence of local invasion and/or distant 
metastases (P<0.001). Moreover, there was a tendency for CD99-reactive tumours 
to show a reduced proliferative activity expressed by a Ki67 index of 2% 
(P=0.119). The number of CD99 immunoreactive cells or patterns of 
immunoreactivity did not correlate with the presence of associated clinical 
syndrome or particular hormonal immunostaining. Although the molecular basis 
underlying CD99 expression in neuroendocrine tumours is still poorly understood, 
our data suggest that CD99 may be involved in cell-to-cell adhesion of 
neuroendocrine tumour cells and in downregulation of their proliferative 
activity.