title: [Anaplastic lymphoma kinase gene abnormality and the expression of its fusion protein in primary systemic anaplastic large cell lymphoma].
abstract: OBJECTIVE
  To study the expression of anaplastic lymphoma kinase (ALK) and chromosome breakage of the anaplastic lymphoma kinase (ALK) gene retrospectively and to investigate their possible value as indicators of prognosis in primary systemic anaplastic large cell lymphomas (S-ALCL).
  
  
  METHODS
  Twenty-eight cases of S-ALCL were collected from the Lymphoma Lab, the Department of Pathology, Peking University Health Science Center and Beijing Children's Hospital. The morphologic characteristics were studied under light microscope, and essential immunohistochemical staininings (IHC) were performed and reviewed to confirm the diagnosis of S-ALCL. ALK-1 monoclonal antibody was used to assess ALK fusion protein expression, and EnVision method was used in IHC. Locus specific interphase fluorescence in situ hybridization (LSI-FISH) was also performed on the neoplastic cells using paraffin-embedded tissues to detect ALK gene abnormality.
  
  
  RESULTS
  ALK-1 protein was expressed in 19 of the 28 cases. In 14 ALCL cases, ALK gene breakage was detected by LSI-FISH, using a dual-color break-apart ALK gene DNA (LSI-ALK) probe. Of the other 14 cases which did not show ALK gene breakage, 5 showed 2 copies of ALK gene as normal, and 9 showed multi-copies of ALK gene. Of all the 28 cases, 22 had complete follow-up materials. Sixteen survived and 6 died, their survival time ranged from 0.5 to 36.0 months, and the survival time on average was 12.8 months, cumulative proportion survival rate was 73.9% in the 1st year. Those cases showing multi-copies of ALK gene might have the worst outcome, with only 47.6% of cumulative proportion survival rate in the 1st year.
  
  
  CONCLUSIONS
  IHC detection for ALK fusion protein is important to the diagnosis of S-ALCL. ALK gene breakage detected by interphase LSI-FISH might not be always consistent with abnormal expression of ALK fusion protein. Complex abnormalities of ALK gene exist in S-ALCL cases, and different types of ALK gene might lead to different clinical outcome. Those cases with multi-copies of ALK gene probably have the poorest prognosis.
authors.affiliation: Department of Pathology, Peking University School of Basic Medical Sciences, Beijing, China.
authors.forename: Yun-fei
authors.initials: YF
authors.lastname: Shi
authors.forename: Cui-ling
authors.initials: CL
authors.lastname: Liu
authors.forename: Chun-ju
authors.initials: CJ
authors.lastname: Zhou
authors.forename: Li-ping
authors.initials: LP
authors.lastname: Gong
authors.forename: Li-na
authors.initials: LN
authors.lastname: Dong
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.forename: Zi-fen
authors.initials: ZF
authors.lastname: Gao
mesh_terms: D000293:Adolescent; D000328:Adult; D000077548:Anaplastic Lymphoma Kinase; D002648:Child; D002675:Child, Preschool; D019457:Chromosome Breakage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D017728:Lymphoma, Large-Cell, Anaplastic / Q000235:genetics*; D008875:Middle Aged; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D011993:Recombinant Fusion Proteins; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases