THE VALUE OF NEUROENDOCRINE MARKERS IN NONSMALL CELL LUNG-CANCER - A COMPARATIVE IMMUNOHISTOPATHOLOGIC STUDY

In order to estimate the value of immunohistochemical identification o f neuroendocrine (NE) differentiation markers in non-small cell lung c arcinomas (NSCLCs), we investigated the expression of five neuroendocr ine and neural differentiation-related antigens in 51 NSCLCs. Addition ally, 20 epithelial lung tumors with NE differentiation [15 carcinoids and five small cell lung carcinomas (SCLCs)] and 61 epithelial tumors of various other origin (breast, prostate, colon and head-neck carcin omas) were studied. An indirect two-stage immunoperoxidase method was performed in formalin-fixed and paraffin-embedded tissue specimens, by using commercially available monoclonal antibodies. These antibodies are directed against neuron-specific enolase (NSE), chromogranin-A and Leu-7 which are general markers of NE differentiation, bombesin, whic h is a specific NE secretory product and neurofilament triplet protein (NFTP), an intermediate filament protein of neuronal differentiation. All five markers demonstrated a positive immunoreactivity in NSCLCs, equally distributed to all three histologic subtypes, ranging from 16 to 47% of the cases (NSE 47%, bombesin 21.5%, Leu-7 21.5%, chromograni n-A 18% and NFTP 16%). Most of the carcinoids and SCLCs expressed mult iple or all NE markers. The other four epithelial tumors showed a posi tive immunoreactivity for bombesin, Leu-7 and NFTP, ranging from 11 to 40% of the cases. Chromogranin-A was not expressed in any of these tu mors, whereas NSE was demonstrated only in 17% of breast carcinomas. T he following remarks can be drawn from this study: (1) some NSCLCs sho wed immunophenotypic NE differentiation; (2) among all the markers use d, NSE was the most sensitive (sensitivity, 100%) and chromogranin-a t he most specific (specificity, 100%); and (3) NSE and chromogranin-A a ppear to be the most valuable and useful indicators of probable neuroe ndocrine differentiation in lung epithelial tumors.