PMID- 15887977
OWN - NLM
STAT- MEDLINE
DCOM- 20050823
LR  - 20191122
IS  - 1084-8592 (Print)
IS  - 1084-8592 (Linking)
VI  - 8
IP  - 4
DP  - 2004
TI  - Multi-lineage interrogation of the performance characteristics of a split-signal 
      fluorescence in situ hybridization probe for anaplastic lymphoma kinase gene 
      rearrangements: a study of 101 cases characterized by immunohistomorphology on 
      fixed archival tissue.
PG  - 213-29
AB  - BACKGROUND: Fluorescence in situ hybridization (FISH) can identify chromosomal 
      translocations on fixed archival tissue, but studies cross-validating the utility 
      of FISH on lesions of different cell lineages that harbor similar translocations 
      (e.g. those involving anaplastic lymphoma kinase [ALK]) have not been published. 
      AIM: Our objective was to define the diagnostic utility, performance 
      characteristics, and limitations of a commercially available, split-signal, FISH 
      probe for ALK gene rearrangements on fixed, archived tissue from lesions of 
      diverse cell lineage. STUDY DESIGN: The sensitivity, specificity, and positive 
      and negative predictive values of the Vysis ALK FISH probe were compared with 
      those of the ALK-1 antibody (Dako) in a series of 101 cases, comprising 43 
      hematolymphoid neoplasms, 4 reactive lymphoid controls, 50 non-hematolymphoid 
      (including neuroectodermal, epithelial, myofibroblastic, and germ cell) lesions, 
      and 4 early-trimester aborted fetuses that served as neuroblastic controls. 
      METHODS: The study involved a predominantly (72%) Singaporean Chinese population 
      aged between 9 months and 88 years (excluding the aborted fetal controls). All 
      cases were reviewed both histologically and immunohistochemically with a wide 
      panel of antibodies using the standard protocols in order to diagnose them 
      according to the latest WHO classification systems. A positive cut-off value was 
      determined, both by comparison with diagnostic categories with and without ALK 
      translocations, as well as with negative controls. RESULTS: The ALK FISH probe 
      suffered a 33% non-informative rate, but in informative cases it showed 94% 
      concordance with the ALK-1 immunostain. A minimum cut-off value of 5 in 200 
      informative cells was adopted to make a positive call in each case. Of the ALK-1 
      immunoreactive lesions, nine lymphomas were concordantly ALK 
      translocation-positive but one vesical inflammatory myofibroblastic tumor was 
      discordantly FISH-negative. Among the ALK-1-immunonegative lesions, one case each 
      of anaplastic lymphoma and pulmonary mycobacterial spindle cell pseudotumor were 
      discordantly ALK FISH-positive, while a case each of intestinal myeloblastic 
      tumor and ganglioglioma showed initial--but not reproducible--positive FISH 
      readings. The remaining cases were concordantly negative. DISCUSSION: The 
      discrepancies between ALK FISH results and well-established immunomorphological 
      parameters indicate that interpretation is not always straightforward. Notably, 
      the derivation of threshold cut-off values for positive calls on FISH assays has 
      seldom been addressed in the literature, and has raised issues in interpreting 
      cases with borderline positivity in this study. The factors that may influence 
      such cut-off values are extensively reviewed. CONCLUSIONS: We propose the term 
      'conditional threshold positivity' to encourage the adoption of different cut-off 
      values for making positive calls in lesions of different origin.
FAU - Tan, Leonard Hwan Cheong
AU  - Tan LH
AD  - Department of Pathology, National University of Singapore, Singapore. 
      pattanl@nus.edu.sg
FAU - Do, Elaine
AU  - Do E
FAU - Tan, Soo Yong
AU  - Tan SY
FAU - Chong, Siew Meng
AU  - Chong SM
FAU - Koay, Evelyn Siew Chuan
AU  - Koay ES
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Diagn
JT  - Molecular diagnosis : a journal devoted to the understanding of human disease 
      through the clinical application of molecular biology
JID - 9614965
RN  - 0 (DNA Probes)
RN  - EC 2.7.10.1 (ALK protein, human)
RN  - EC 2.7.10.1 (Anaplastic Lymphoma Kinase)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
EIN - Mol Diagn. 2005;9(2):94
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Anaplastic Lymphoma Kinase
MH  - Case-Control Studies
MH  - Cell Lineage/*genetics
MH  - Child
MH  - Child, Preschool
MH  - DNA Probes/genetics
MH  - Female
MH  - *Gene Rearrangement
MH  - Humans
MH  - *In Situ Hybridization, Fluorescence
MH  - Lymphoid Tissue/pathology
MH  - Middle Aged
MH  - Neoplasms/genetics/pathology
MH  - Predictive Value of Tests
MH  - Pregnancy
MH  - Protein-Tyrosine Kinases/*genetics/immunology
MH  - Receptor Protein-Tyrosine Kinases
MH  - Sensitivity and Specificity
MH  - Threshold Limit Values
EDAT- 2005/05/13 09:00
MHDA- 2005/08/24 09:00
CRDT- 2005/05/13 09:00
PHST- 2005/05/13 09:00 [pubmed]
PHST- 2005/08/24 09:00 [medline]
PHST- 2005/05/13 09:00 [entrez]
AID - 843 [pii]
AID - 10.1007/BF03260066 [doi]
PST - ppublish
SO  - Mol Diagn. 2004;8(4):213-29. doi: 10.1007/BF03260066.