Immunohistochemical detection of neuroendocrine markers in tumors of the lungs and gastrointestinal tract

Using immunohistochemistry, we investigated neuroendocrine markers in resec tion specimens from 94 carcinoids, small cell carcinomas, adenocarcinomas, and solid carcinomas of the lungs (n = 45) and gut (n = 49). The expression of chromogranin A, synaptophysin, neuron-specific enolase, protein gene pr oduct 9.5, and cystatin C in tumors with and without histologic characteris tics of neuroendocrine differentiation was registered semiquantitatively. U nexpected immunoreactions in nontumor cells were recorded. Positive stainin g for chromogranin A and synaptophysin had the highest concordance with a n euroendocrine morphology. Convincing immunoreactivity for chromogranin A wa s seen in 97% of the carcinoids, synaptophysin in 100%. Neuron-specific eno lase, protein gene product 9.5, and cystatin C, on the other hand, had lowe r concordance with a neuroendocrine morphology and they often showed unexpe cted immunostaining in many morphologically nonneuroendocrine tumors and in nontumor cells. We therefore used a positive staining result for chromogra nin A or synaptophysin as evidence for a neuroendocrine immunophenotype. Ba sed on this standard, we estimated the sensitivity and specificity for the other three markers. The overall sensitivity and specificity for neuron-spe cific enolase was 45% and 67%, respectively, for protein gene product 9.5, 67% and 47%, respectively, and for cystatin C 85% and 47%, respectively. We conclude that chromogranin A and synaptophysin show high concordance for n euroendocrine differentiation, whereas the other traditionally used "neuroe ndocrine" markers (neuron-specific enolase, protein gene product 9.5, and c ystatin C), are unreliable.