A COMPARISON OF NSP-RETICULONS WITH CONVENTIONAL NEUROENDOCRINE MARKERS IN IMMUNOPHENOTYPING OF LUNG CANCERS

Neuroendocrine-specific protein (NSP)-reticulons are endoplasmic retic ulum-associated protein complexes, which have been identified as marke rs for neuroendocrine differentiation. In this study, the expression o f two members of the family of NSP-reticulons, NSP-A and NSP-C, have b een investigated in different types of lung cancer and compared with t he expression patterns of five conventional neuroendocrine markers, th e neural cell. adhesion molecule (NCAM), synaptophysin, chromogranin A , Leu-7, and neurofilament proteins. NSP-A and NSP-C antibodies were r eactive with most carcinoid tumour and small cell lung carcinoma (SCLC ) cases, while atypical carcinoid rumours showed a variable expression . In the total group of neuroendocrine tumours, a high concordance of expression was found between NSP-A and NSP-C, while their expression c orrelated well with NCAM and synaptophysin positivity. Chromogranin A, Leu-7, and neurofilament proteins were shown to be expressed to a lim ited extent in these neuroendocrine rumours. In a selected group of no n-SCLCs known to exhibit neuroendocrine features, NSP-A expression was detected at much higher frequency than NSP-C. In virtually all NSP-A positive cases, this expression was associated with one or more of the other neuroendocine markers. NSP-A expression showed a stronger corre lation with conventional neuroendocrine markers than NCAM. In detectin g neuroendocrine differentiation in, non-SCLC, NSP-A is more sensitive than synaptophysin, chromogranin A, Leu-7, and neurofilament proteins . It is concluded that NSP-reticulons are valuable markers in the diag nosis of neuroendocrine differentiation in non-SCLC and should be used in conjunction with NCAM. (C) 1997 by John Wiley & Sons, Ltd.