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Prognostic implications of anaplastic lymphoma kinase gene aberrations in rhabdomyosarcoma; an immunohistochemical and fluorescence in situ hybridisation study
  1. Jae Seok Lee1,
  2. Sun Min Lim2,
  3. Sun Young Rha2,
  4. Jae Kyung Roh2,
  5. Yong Jin Cho3,
  6. Kyu Ho Shin3,
  7. Woo Ik Yang1,
  8. Se Hoon Kim1,
  9. Hyo Song Kim2
  1. 1Department of Pathology, Yonsei University College of Medicine, Seoul, Korea
  2. 2Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
  3. 3Department of Orthopedic Surgery, Yonsei University College of Medicine, Seoul, Korea
  1. Correspondence to Dr Hyo Song Kim, Division of Medical Oncology, Department of Medicine, College of Medicine, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea; HYOSONG77{at}YUHS.AC and Dr Se Hoon Kim, Department of Pathology, College of Medicine, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea; paxco{at}yuhs.ac

Abstract

Background We investigated the diagnostic and prognostic usefulness of anaplastic lymphoma kinase (ALK) expression in Asian rhabdomyosarcoma (RMS) patients.

Patients and methods A total of 38 RMS tissue samples were collected over a 14-year period (1998–2012). ALK protein expression and gene copy number were analysed by immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH).

Results Ten of the 38 RMS patients (26.3%) showed positive ALK protein expression. ALK protein expression was predominantly positive in alveolar RMS (ARMS) compared with embryonal RMS (ERMS) (80% vs 20%, p=0.03). ALK protein expression was statistically associated with ARMS histology, metastatic disease at diagnosis, and primary trunk site. In FISH analysis, no translocations were detected and ALK gene copy number gain was observed more frequently in ARMS than in ERMS (40% vs 17%). The ALK-positive group showed inferior overall survival (OS) compared with ALK-negative group (p=0.014) for both alveolar and embryonal RMS patients. In multivariate analysis, positive ALK expression was an independent prognostic factor for OS (p=0.02; HR, 3.1; 95% CI 1.2 to 8.3). There was a significant strong positive correlation between ALK gene copy number and protein expression (Spearman's r<0.001, r=0.77).

Conclusions We demonstrated that ALK protein expression is statistically associated with ARMS histology, metastatic disease at diagnosis and primary trunk site. Additionally, ALK expression was an independent prognostic factor for worse survival. There was a strong correlation between IHC and FISH. Further studies are needed to evaluate the potential diagnostic and therapeutic role of ALK expression in RMS.

  • Rhabdomyosarcoma
  • Fish
  • Immunocytochemistry

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