Poster Presentation Advances in Neuroblastoma Research Congress 2016

A High ALK expression is associated with an unfavorable histology in Neuroblastoma. (#267)

Atsuko Nakazawa 1 , Kumiko Uryu 2 , Chizuko Haga 1 , Hajime Okita 3 , Tetsuya Takimoto 4 , Tatsuro Tajiri 5 , Akira Nakagawara 5 , Seishi Ogawa 6 , Junko Takita 2
  1. Pathology, Tokai University, School of Medicine, Isehara, Kanagawa, Japan
  2. Pediatrics, The University of Tokyo, Tokyo, Japan
  3. Pathology, Keio University, Tokyo, Japan
  4. Clinical Research Center, National Center for Child Health and Development, Tokyo, Japan
  5. Japan Neuroblastoma Study Group, Japan
  6. Pathology and Tumor Biology, Kyoto University, Kyoto, Japan

Back ground

A high ALK protein expression, unfavorable histology (UH) according to the International Neuroblastoma Pathology Classification (INPC) and MYCN amplification are associated with a poor outcome in neuroblastoma (NB). Correlations between a high ALK expression and histology are inconclusive.

 

Method

Immunohistochemistry for ALK and INPC was evaluated in 195 NBs analyzed for MYCN amplification, 1p/11q LOH, 17q gain, and ALK mutations. Over 50% positivity of tumor cells indicated a high ALK expression. Correlations between the ALK expression and INPC and genomic alteration(s) were analyzed for prognostic significance.

 

Results

Eighty-six NBs with high ALK expression levels and 109 NBs with low ALK expression levels were identified. High ALK expressors significantly demonstrated UH (70/86, p<0.0001). MYCN amplification and 11q LOH were not associated with high ALK expression levels. High ALK expressors with a favorable histology (FH) were younger than those with UH; median age at diagnosis was 6.5 months and 36.5 months, respectively. Among ALK high expressors, ALK mutations were detected in 12/70 (17%) in the UH group, and 4/16 (25%) in the FH group. In the FH group, high ALK expressors showed a significantly inferior overall survival rate (OS)(58%) than low ALK expressors (100%) (p=0.001), while ALK expression was not associated with the prognosis in UH (OS was 41% and 50%, respectively). FH and MYCN nonamplified (NA) tumors showed less ALK high expression (14/65; 22%) and 11q LOH (9/65; 14%)(p<0.0001). UH and MYCN-NA tumors tended to exhibit 11q LOH (43/70; 61%)(p=0.056), but not a high ALK expression. UH and MYCN amplified tumors were associated with high ALK expression levels (36/56; 64%)(p=0.033) and less 11q LOH (9/56; 16%)(p<0.0001).

 

Conclusion

A high expression of ALK correlated with UH, but not MYCN amplification or 11q LOH. In the FH group, but not in UH, high ALK expressors had an inferior survival.