ICAM-2 Limits Metastasis amplification status of the MYCN gene, age, and stage [28]. Patients with favorable histology low risk tumors have a greater than 95% overall survival with no adjuvant therapy beyond surgery. In contrast, patients with unfavorable histology and MYCN-amplified tumors have a ,20% 5-year survival despite intensive therapy. Each tumor in the TMA was designated to have a ‘‘good’’ or ‘‘poor’’ prognosis based on histopathology, age at diagnosis, MYCN copy number status, and stage. The first three parameters were assessed in line with the criteria adopted by the International Neuroblastoma Pathology Committee, based on the Shimada classification [35]. With respect to histopathology, the most immature primary neuroblastoma cells (neuroblasts) are characterized by small size and scant cytoplasm. This undifferentiated cell type is usually associated with high-risk disease and less favorable clinical outcome. On the other extreme are cells with obvious advanced ganglionic differentiation, with abundant cytoplasm that includes a prominent basophilic golgi body area and a round eccentric nucleus with a prominent nucleolus. Primary tumor cells exhibit varying degrees of ganglionic differentiation. Cells with advanced ganglionic differen- tiation are associated with lower-risk disease and favorable clinical outcome. The presence of abundant stromal tissue (Schwannian stroma), is also usually associated with a more favorable prognosis. These criteria, in conjunction with age and tumor staging information provided by the Children’s Oncology Group Biological Studies Oversight Committee formed the basis of designation of tumors in Table 1 as having ‘‘good’’ or ‘‘poor’’ prognosis. A summary of the results for the staining of the 89 interpretable specimens (Table 1) showed that 42% (37 of 89) of primary tumors Table 1. Characteristics of tumors evaluated for ICAM-2 expression. ICAM-2 score ,30 ICAM-2 score $30 & #90* ICAM-2 score $160 & #300 24 16 (67%) 8 (33%) 19 (79%) 2 (8%) 0 (0%) 0 (0%) 3 (13%) 13 (54%) 0 (0%) 11 (46%) 3 (13%) 3 (13%) 2 (8%) 9 (38%) 6 (25%) 0 (0%) 1 (4%) 7 (29%) 10 (42%) 3 (13%) 0 (0%) 4 (17%) 19 (83%) 4 (17%) 15 (63%) 6 (25%) 3 (13%) N Gender Male Female Race White Black Hispanic Filipino Age ,1 year Stage 2/2A/2B 1 3 4 4S Unknown or other $1 year - #18 months .18 months Stage not available (GN patients) Shimada Pathology Favorable Histology/GN Unfavorable Histology Post-Treatment Post-Treatment (UH by age) Unknown/missing Prognosis^ Good Poor ICAM-2 expressed by: Differentiated ganglionic cells Both differentiated cells and undifferentiated neuroblasts Neuroblasts *No specimens received a score of .90 & ,160. ^ As defined in References 28, 34, and 35, and explained in the text. doi:10.1371/journal.pone.0003629.t001 PLoS ONE | www.plosone.org 9 November 2008 | Volume 3 | Issue 11 | e3629 52 32 (62%) 20 (38%) 45 (87%) 1 (2%) 2 (4%) 1 (2%) 3 (6%) 25 (48%) 3 (6%) 24 (46%) 5 (10%) 9 (17%) 8 (15%) 18 (35%) 9 (17%) 1 (2%) 2 (4%) 17 (33%) 19 (37%) 3 (6%) 1 (2%) 12 (23%) 13 9 (69%) 4 (31%) 9 (69%) 1 (8%) 0 (0%) 0 (0%) 3 (23%) 4 (31%) 0 (0%) 9 (69%) 3 (23%) 2 (15%) 3 (23%) 4 (31%) 1 (8%) 0 (0%) 0 (0%) 5 (38%) 7 (54%) 0 (0%) 0 (0%) 1 (8%) 4 (31%) 6 (46%) 3 (23%)