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. 2016 Nov;186(11):3040–3053. doi: 10.1016/j.ajpath.2016.07.019

Figure 1.

Figure 1

Undifferentiated neuroblastoma (NB) tumors synthesize and release high levels of neuropeptide Y (NPY). A: Variability in serum NPY concentrations, measured by enzyme-linked immunosorbent assay, among patients with neuroblastic tumors. The solid line represents the median NPY level (0.69 ng/mL). B: Elevated serum NPY levels in patients with undifferentiated or poorly differentiated tumors (median, 0.75 ng/mL) compared with those with differentiating tumors (median, 0.35 ng/mL). C: NPY mRNA levels, measured by real-time RT-PCR, are significantly higher in tissues from undifferentiated or poorly differentiated tumors compared with differentiating NBs. D: In patients with neuroblastic tumors, serum NPY concentrations positively correlate with its tumor mRNA levels. The statistical analysis was performed on ΔCT values (r = −0.3215); however, the mRNA levels shown on the graph were converted to fold increase over β-actin according to the formula 2−ΔCT to illustrate the positive direction of the correlation. E–G: Representative micrographs of NB tissues at different grades of histological differentiation stained with hematoxylin and eosin (H&E, top row) and anti-NPY antibody (NPY, bottom row). In undifferentiated tumors, a significant amount of NPY is detectable in extracellular spaces and at the cytoplasmic level (E), whereas maturing cells in differentiating NBs (F) and mature ganglion cells in ganglioneuromas (GNs) (G) accumulate NPY in the cytoplasm (red arrows). Data are presented as box plots representing range (vertical lines), 25th and 75th percentile (bottom and top of the box, respectively), and median value (solid horizontal line within the box) (B and C). n = 83 (A); n = 68 (B, undifferentiated or poorly differentiated tumors); n = 11 (B, differentiating tumors); n = 69 (C, undifferentiated or poorly differentiated tumors); n = 10 (C, differentiating NBs); n = 79 (D). ∗P < 0.05, ∗∗P < 0.01. Scale bar = 200 μm. Original magnification: ×200 (E–G, main images); ×400 (insets). H&E, hematoxylin and eosin.