Neuroendocrine phenotype of non-small cell lung carcinoma: immunohistological evaluation and biochemical study.
OBJECTIVE
The prevalence and distribution of neuroendocrine differentiation in non-small cell lung cancer (NSCLC) was estimated by assays for synaptophysin (SYN), chromogranin A (CgA), Leu7 and neuron-specific enolase (NSE). Serum NSE and CgA were determined in parallel to find the values of these markers for distinguishing neuroendocrine differentiation in NSCLC. Fifty-eight resected NSCLC specimens and 34 sera of NSCLC patients entered the study. Neuroendocrine differentiation was graded according to the percentage of neuroendocrine tumor cells as NE0--0%, NE1-NE4--1%->76%. Serum NSE <12.5 ng/mL and serum CgA <46 U/L were taken as cutoff levels.


RESULTS
63.8% (37/58) of NSCLC were scored as NE1-NE4 according to the SYN, CgA and Leu7 levels; 34.5% as NE1; 29.3% as NE2-NE4. 56.8% of tumors were positive for SYN, 34.4% for CgA, 22.4% for Leu7, and 79.3% for NSE. A significant relationship was found between tumor SYN and tumor CgA expression, and between tumor SYN expression and tumor stage. Adenocarcinomas showed a significantly higher rate of neuroendocrine differentiation than squamous cell carcinomas. All normal serum CgA levels corresponded to a lack of CgA expression in the tumors. The increased serum NSE levels presented by 26% of NSCLC patients (mainly <16 ng/mL) did not correlate with tumor NSE expression.


CONCLUSIONS
The prevalence of neuroendocrine differentiation in NSCLC varies and depends on the immunohistochemical criteria used; this warrants standardization of the immunohistochemical criteria for neuroendocrine differentiation in NSCLC. NSE expression in the tumor and a mild increase in serum NSE are poor markers for distinguishing neuroendocrine differentiation in NSCLC.
Slodkowska
J
J
Department of Telepathology, The National Tuberculosis and Lung Diseases Research Institute, Warsaw, Poland. j.slodkowska@igichp.edu.pl
Zych
J
J
Szturmowicz
M
M
Demkow
U
U
Rowinska-Zakrzewska
E
E
Roszkowski-Sliz
K
K
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009490:Neurosecretory Systems / Q000276:immunology* / Q000378:metabolism*; D010641:Phenotype
D014408:Biomarkers, Tumor