The value of neuroendocrine markers in non-small cell lung cancer: a comparative immunohistopathologic study.
In order to estimate the value of immunohistochemical identification of neuroendocrine (NE) differentiation markers in non-small cell lung carcinomas (NSCLCs), we investigated the expression of five neuroendocrine and neural differentiation-related antigens in 51 NSCLCs. Additionally, 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 carcinomas) 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, which 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%, chromogranin-A 18% and NFTP 16%). Most of the carcinoids and SCLCs expressed multiple or all NE markers. The other four epithelial tumors showed a positive immunoreactivity for bombesin, Leu-7 and NFTP, ranging from 11 to 40% of the cases. Chromogranin-A was not expressed in any of these tumors, whereas NSE was demonstrated only in 17% of breast carcinomas. The following remarks can be drawn from this study: (1) some NSCLCs showed immunophenotypic NE differentiation; (2) among all the markers used, NSE was the most sensitive (sensitivity, 100%) and chromogranin-A the most specific (specificity, 100%); and (3) NSE and chromogranin-A appear to be the most valuable and useful indicators of probable neuroendocrine differentiation in lung epithelial tumors.
Kiriakogiani-Psaropoulou
P
P
Agii Anargyri Cancer Hospital, Athens, Greece.
Malamou-Mitsi
V
V
Martinopoulou
U
U
Legaki
S
S
Tamvakis
N
N
Vrettou
E
E
Fountzilas
G
G
Skarlos
D
D
Kosmidis
P
P
Pavlidis
N
N
D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D001839:Bombesin / Q000032:analysis; D018959:CD57 Antigens; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D053379:Chromogranin A; D002864:Chromogranins / Q000032:analysis; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000473:pathology*; D016900:Neurofilament Proteins / Q000032:analysis; D010751:Phosphopyruvate Hydratase / Q000032:analysis
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D014408:Biomarkers, Tumor; D018959:CD57 Antigens; D053379:Chromogranin A; D002864:Chromogranins; D016900:Neurofilament Proteins; D010751:Phosphopyruvate Hydratase; D001839:Bombesin