Primary tumors with Ch11q deletions presented higher COX-2
expression levels
Array-CGH analysis in the paired sample sets (n = 11) revealed that the
median (min-max) of the CNAs in each case did not significantly differ
between the pre-CT [14.5 (3–47)] and post-CT [9 (2–29)]
(p-value = 0.3813) (Figure 2A). The most frequent aberrant cytobands
(present in at least 50% of cases) were compared in the paired samples
(Figure 2B). The cytobands that (i) correlated with COX-2 expression in
the multivariate analysis, (ii) were within the chromosomal regions that
code for COX-2/PGE2 pathway proteins, and (iii) have prognostic
relevance to NBs (cytobands 2p24, 11q12-q25, and 17q11-q25)35. CNAs distribution and frequency varied randomly
between pre-CT and post-CT tumor samples. Cytobands 7p22-p15, 7q11-q36
(gain), and 10q11-q26 (loss) were mainly or exclusively found in the
pre-CT samples. In contrast, CNAs were observed in a higher frequency
after chemotherapy in the 2p (36%), 4p (63%), 14q (72%), and 17q
(54%). Positive correlations between
COX-2 expression levels and 7p gain (ρ = 0.798; p-value = 0.006),
7q gain (ρ = 0.853; p-value = 0.002), and 11q loss (ρ =
0.631, p=0.045) were observed. These cases were then segregated into
three groups based on MYCN amplification status and Ch11q
deletion: amplified MYCN with normal Ch11q
(MNA/11qN, Group 1), non-amplified MYCN with
loss in Ch11q (NAMN/11q-, Group 2), and non-amplifiedMYCN with normal Ch11q (NAMN/11qN, Group 3)
(Table 2). In general, Groups 1 and 2 were classified as unfavorable
NBs, although in Group 2, a higher number of CNAs and higher COX-2
expression were observed in comparison with Group 1.