PMID- 31493794
OWN - NLM
STAT- MEDLINE
DCOM- 20200312
LR  - 20200312
IS  - 1746-1596 (Electronic)
IS  - 1746-1596 (Linking)
VI  - 14
IP  - 1
DP  - 2019 Sep 7
TI  - OLIG2 is a novel immunohistochemical marker associated with the presence of 
      PAX3/7-FOXO1 translocation in rhabdomyosarcomas.
PG  - 103
LID - 10.1186/s13000-019-0883-4 [doi]
LID - 103
AB  - BACKGROUND: The most frequent histological types of rhabdomyosarcoma (RMS) in 
      children are embryonal (ERMS) and alveolar (ARMS) tumours. The majority of ARMS 
      are characterized by the presence of PAX3/7-FOXO1 gene fusion and have a worse 
      prognosis than fusion gene-negative ARMS. However, identification of PAX3/7-FOXO1 
      fusion status is challenging when using formalin-fixed, paraffin-embedded (FFPE) 
      material. Microarray analyses revealed that high expression of several genes is 
      associated with PAX3/7-FOXO1 fusion status. Therefore, we investigated if 
      immunohistochemical approach may detect surrogate marker genes as indicators of 
      fusion gene-positive RMS. METHODS: Forty five RMS patients were included in the 
      analysis and immunohistochemistry was applied to FFPE tissues collected at 
      diagnosis. Protein expression of OLIG2, a novel marker in RMS, was investigated 
      using antibody EP112 (Cell Marque). In addition already known two markers were 
      also analyzed: TFAP2B using rabbit anti-TFAP2beta antibody (Santa Cruz 
      Biotechnology) and ALK using anti-ALK antibody clone D5F3 #3633 (Cell 
      Signalling). Fluorescence in situ hybridization (FISH) was performed on FFPE 
      sections with FOXO1/PAX3 and/or FOXO1/PAX7 probes (Dual Colour Single Fusion 
      Probe, Zytovision). RESULTS: Our analysis revealed that all three 
      immunohistochemical markers are associated with the presence of PAX3/7-FOXO1 
      fusion: TFAP2B (p < 0.00001), OLIG2 (p = 0.0001) and ALK (p = 0.0007). Four ARMS 
      had negative PAX3/7-FOXO1 status and none of them displayed positive reaction 
      with the analysed markers. Positive reaction with OLIG2 (6 tumours) was always 
      associated with the presence of PAX3/7-FOXO1 rearrangement. Two additional OLIG2 
      positive cases showed inconclusive FISH results, but were positive for TFAP2B and 
      ALK, what suggests that these tumours expressed fusion positive signature. 
      CONCLUSION: Our results indicate that TFAP2B, ALK and a novel marker OLIG2 may 
      serve as surrogate markers for PAX3/7-FOXO1 status what is especially beneficial 
      in cases where poor quality tumour tissue is not suitable for reliable genetic 
      analyses or shows inconclusive result.
FAU - Kaleta, Magdalena
AU  - Kaleta M
AD  - Department of Pathology, The Children's Memorial Health Institute, Av. Dzieci 
      Polskich 20, 04-730, Warsaw, Poland. m.kaleta@ipczd.pl.
FAU - Wakulinska, Anna
AU  - Wakulinska A
AD  - Clinic of Oncology, The Children's Memorial Health Institute, Av. Dzieci Polskich 
      20, 04-730, Warsaw, Poland.
FAU - Karkucinska-Wieckowska, Agnieszka
AU  - Karkucinska-Wieckowska A
AD  - Department of Pathology, The Children's Memorial Health Institute, Av. Dzieci 
      Polskich 20, 04-730, Warsaw, Poland.
FAU - Dembowska-Baginska, Bozenna
AU  - Dembowska-Baginska B
AD  - Clinic of Oncology, The Children's Memorial Health Institute, Av. Dzieci Polskich 
      20, 04-730, Warsaw, Poland.
FAU - Grajkowska, Wieslawa
AU  - Grajkowska W
AD  - Department of Pathology, The Children's Memorial Health Institute, Av. Dzieci 
      Polskich 20, 04-730, Warsaw, Poland.
FAU - Pronicki, Maciej
AU  - Pronicki M
AD  - Department of Pathology, The Children's Memorial Health Institute, Av. Dzieci 
      Polskich 20, 04-730, Warsaw, Poland.
FAU - Lastowska, Maria
AU  - Lastowska M
AD  - Department of Pathology, The Children's Memorial Health Institute, Av. Dzieci 
      Polskich 20, 04-730, Warsaw, Poland.
LA  - eng
GR  - Grant no 239/16/Internal Funding from The Children's Memorial Health Institute, 
      Warsaw, Poland/
PT  - Journal Article
DEP - 20190907
PL  - England
TA  - Diagn Pathol
JT  - Diagnostic pathology
JID - 101251558
RN  - 0 (Biomarkers)
RN  - 0 (FOXO1 protein, human)
RN  - 0 (Forkhead Box Protein O1)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (OLIG2 protein, human)
RN  - 0 (Oligodendrocyte Transcription Factor 2)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (PAX3 Transcription Factor)
RN  - 0 (PAX3 protein, human)
RN  - 0 (Paired Box Transcription Factors)
SB  - IM
MH  - Adolescent
MH  - Biomarkers/analysis
MH  - Child
MH  - Child, Preschool
MH  - Female
MH  - Forkhead Box Protein O1/metabolism
MH  - Forkhead Transcription Factors/genetics
MH  - Humans
MH  - *Immunohistochemistry/methods
MH  - In Situ Hybridization, Fluorescence/methods
MH  - Infant
MH  - Male
MH  - Oligodendrocyte Transcription Factor 2/*metabolism
MH  - Oncogene Proteins, Fusion/genetics
MH  - PAX3 Transcription Factor/metabolism
MH  - Paired Box Transcription Factors/metabolism
MH  - Rhabdomyosarcoma/*diagnosis/*metabolism
PMC - PMC6731563
OTO - NOTNLM
OT  - ALK
OT  - Immunohistochemistry
OT  - OLIG2
OT  - Rhabdomyosarcoma
OT  - TFAP2B
COIS- The authors declare that they have no competing interests.
EDAT- 2019/09/09 06:00
MHDA- 2020/03/13 06:00
PMCR- 2019/09/07
CRDT- 2019/09/09 06:00
PHST- 2019/07/04 00:00 [received]
PHST- 2019/09/02 00:00 [accepted]
PHST- 2019/09/09 06:00 [entrez]
PHST- 2019/09/09 06:00 [pubmed]
PHST- 2020/03/13 06:00 [medline]
PHST- 2019/09/07 00:00 [pmc-release]
AID - 10.1186/s13000-019-0883-4 [pii]
AID - 883 [pii]
AID - 10.1186/s13000-019-0883-4 [doi]
PST - epublish
SO  - Diagn Pathol. 2019 Sep 7;14(1):103. doi: 10.1186/s13000-019-0883-4.