Abstract B40: MYCN/MYC protein expression in high-MKI (Mitosis-Karyorrhexis Index) neuroblastomas: A report from the Children's Oncology Group

Abstract

Abstract Background: In neuroblastoma (NB), Mitosis-Karyorrhexis Index (MKI; low-L, <100/5,000 cells; intermediate-I, 100-200/5,000 cells; high-H, >200/5,000 cells) is one of the histologic indicators for predicting a patient's clinical outcome. Event-Free Survival (EFS) and Overall Survival (OS) are significantly worse as MKI increases (p<0.0001): 3-year EFS for L-MKI (81.2+1.0%), I-MKI (68.6+1.8%), H-MKI (51.0+2.2%); and 3-year OS for L-MKI (92.0+0.7%), I-MKI (81.0+1.6%), H-MKI (64.4+2.1%). MYCN amplification (MYCN-A) is significantly associated with H-MKI, which indicates markedly increased mitotic (cellular proliferation) and karyorrhectic (cellular death) cells. However, about one-third of H-MKI tumors do not have MYCN-A. Study design: A total of 4,712 NB cases reviewed by the Children's Oncology Group (COG) Neuroblastoma Pathology Reference Laboratory (Children's Hospital Los Angeles) between 06/18/2001 and 06/06/2013 included 2,595 L-MKI (3% with MYCN-A), 1,197 I-MKI (16% with MYCN-A), and 920 H-MKI (70% with MYCN-A) tumors. In this study, immunohistochemical detection of MYCN and MYC (C-myc) protein was performed on 82 H-MKI tumors (53 with MYCN-A and 29 without MYCN-A). Results: 50/53 (94%) of H-MKI tumors having MYCN-A were positive for MYCN protein (including one case positive for both MYCN and MYC proteins), and only 3 cases were negative for both proteins immunohistochemically. Among the H-MKI tumors without MYCN-A, 16 cases (55%) showed positive staining for MYC protein, 6 cases (21%) were positive for MYCN protein, 2 cases (7%) were positive for both proteins, and 5 cases (17%) were negative for both proteins. Conclusions: MYCN-A and subsequent MYCN protein expression are considered as the starting point for leading NB tumors to H-MKI status. However, when MYCN is not amplified, high mitotic/karyorrhectic (M/K) activities in NB tumors are often associated with MYC protein expression. Even some MYCN non-amplified tumors can express MYCN protein, which is associated with H-MKI. There is still a small group of H-MKI tumors whose increased M/K activities are not related to MYCN/MYC protein expression. Citation Format: Larry L. Wang, Risa Teshiba, Lejian He, Arlene Naranjo, Wendy B. London, Julie M. Gastier-Foster, Robert C. Seeger, Susan L. Cohn, John M. Maris, Julie R. Park, Michael D. Hogarty, Hiroyuki Shimada. MYCN/MYC protein expression in high-MKI (Mitosis-Karyorrhexis Index) neuroblastomas: A report from the Children's Oncology Group. [abstract]. In: Proceedings of the AACR Special Conference on Pediatric Cancer at the Crossroads: Translating Discovery into Improved Outcomes; Nov 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;74(20 Suppl):Abstract nr B40.