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.