PMID- 25698220
OWN - NLM
STAT- MEDLINE
DCOM- 20150522
LR  - 20211203
IS  - 1479-683X (Electronic)
IS  - 0804-4643 (Linking)
VI  - 172
IP  - 5
DP  - 2015 May
TI  - Break-apart interphase fluorescence in situ hybridization assay in papillary 
      thyroid carcinoma: on the road to optimizing the cut-off level for RET/PTC 
      rearrangements.
PG  - 571-82
LID - 10.1530/EJE-14-0930 [doi]
AB  - OBJECTIVE: Chromosomal rearrangements of the RET proto-oncogene is one of the 
      most common molecular events in papillary thyroid carcinoma (PTC). However, their 
      pathogenic role and clinical significance are still debated. This study aimed to 
      investigate the prevalence of RET/PTC rearrangement in a cohort of BRAF WT PTCs 
      by fluorescence in situ hybridization (FISH) and to search a reliable cut-off 
      level in order to distinguish clonal or non-clonal RET changes. DESIGN: Forty 
      BRAF WT PTCs were analyzed by FISH for RET rearrangements. As controls, six 
      BRAFV600E mutated PTCs, 13 follicular adenomas (FA), and ten normal thyroid 
      parenchyma were also analyzed. METHODS: We performed FISH analysis on 
      formalin-fixed, paraffin-embedded tissue using a commercially available RET 
      break-apart probe. A cut-off level equivalent to 10.2% of aberrant cells was 
      accepted as significant. To validate FISH results, we analyzed the study cohort 
      by qRT-PCR. RESULTS: Split RET signals above the cut-off level were observed in 
      25% (10/40) of PTCs, harboring a percentage of positive cells ranging from 12 to 
      50%, and in one spontaneous FA (1/13, 7.7%). Overall, the data obtained by FISH 
      matched well with qRT-PCR results. Challenging findings were observed in five 
      cases showing a frequency of rearrangement very close to the cut-off. 
      CONCLUSIONS: FISH approach represents a powerful tool to estimate the ratio 
      between broken and non-broken RET tumor cells. Establishing a precise FISH 
      cut-off may be useful in the interpretation of the presence of RET rearrangement, 
      primarily when this strategy is used for cytological evaluation or for targeted 
      therapy.
CI  - (c) 2015 European Society of Endocrinology.
FAU - Colato, Chiara
AU  - Colato C
AD  - Department of Pathology and DiagnosticsARC-NET Research CentreUniversity of 
      Verona, Policlinico GB Rossi, Piazzale LA Scuro, 10, Piastra Odontoiatrica (II 
      floor), 37134 Verona, ItalyDepartment of Internal MedicineEndocrinology, and 
      Metabolism and Biochemistry, University of Siena, Siena, ItalyDepartment of 
      Surgery and OncologyUniversity of Verona, Verona, ItalyDivision of 
      SurgicalMolecular and Ultrastructural, Section of Cytopathology, University 
      Hospital of Pisa, Pisa, ItalyNuclear Medicine UnitUniversity Hospital of Verona, 
      Verona, Italy chiara.colato@ospedaleuniverona.it.
FAU - Vicentini, Caterina
AU  - Vicentini C
AD  - Department of Pathology and DiagnosticsARC-NET Research CentreUniversity of 
      Verona, Policlinico GB Rossi, Piazzale LA Scuro, 10, Piastra Odontoiatrica (II 
      floor), 37134 Verona, ItalyDepartment of Internal MedicineEndocrinology, and 
      Metabolism and Biochemistry, University of Siena, Siena, ItalyDepartment of 
      Surgery and OncologyUniversity of Verona, Verona, ItalyDivision of 
      SurgicalMolecular and Ultrastructural, Section of Cytopathology, University 
      Hospital of Pisa, Pisa, ItalyNuclear Medicine UnitUniversity Hospital of Verona, 
      Verona, Italy.
FAU - Cantara, Silvia
AU  - Cantara S
AD  - Department of Pathology and DiagnosticsARC-NET Research CentreUniversity of 
      Verona, Policlinico GB Rossi, Piazzale LA Scuro, 10, Piastra Odontoiatrica (II 
      floor), 37134 Verona, ItalyDepartment of Internal MedicineEndocrinology, and 
      Metabolism and Biochemistry, University of Siena, Siena, ItalyDepartment of 
      Surgery and OncologyUniversity of Verona, Verona, ItalyDivision of 
      SurgicalMolecular and Ultrastructural, Section of Cytopathology, University 
      Hospital of Pisa, Pisa, ItalyNuclear Medicine UnitUniversity Hospital of Verona, 
      Verona, Italy.
FAU - Pedron, Serena
AU  - Pedron S
AD  - Department of Pathology and DiagnosticsARC-NET Research CentreUniversity of 
      Verona, Policlinico GB Rossi, Piazzale LA Scuro, 10, Piastra Odontoiatrica (II 
      floor), 37134 Verona, ItalyDepartment of Internal MedicineEndocrinology, and 
      Metabolism and Biochemistry, University of Siena, Siena, ItalyDepartment of 
      Surgery and OncologyUniversity of Verona, Verona, ItalyDivision of 
      SurgicalMolecular and Ultrastructural, Section of Cytopathology, University 
      Hospital of Pisa, Pisa, ItalyNuclear Medicine UnitUniversity Hospital of Verona, 
      Verona, Italy.
FAU - Brazzarola, Paolo
AU  - Brazzarola P
AD  - Department of Pathology and DiagnosticsARC-NET Research CentreUniversity of 
      Verona, Policlinico GB Rossi, Piazzale LA Scuro, 10, Piastra Odontoiatrica (II 
      floor), 37134 Verona, ItalyDepartment of Internal MedicineEndocrinology, and 
      Metabolism and Biochemistry, University of Siena, Siena, ItalyDepartment of 
      Surgery and OncologyUniversity of Verona, Verona, ItalyDivision of 
      SurgicalMolecular and Ultrastructural, Section of Cytopathology, University 
      Hospital of Pisa, Pisa, ItalyNuclear Medicine UnitUniversity Hospital of Verona, 
      Verona, Italy.
FAU - Marchetti, Ivo
AU  - Marchetti I
AD  - Department of Pathology and DiagnosticsARC-NET Research CentreUniversity of 
      Verona, Policlinico GB Rossi, Piazzale LA Scuro, 10, Piastra Odontoiatrica (II 
      floor), 37134 Verona, ItalyDepartment of Internal MedicineEndocrinology, and 
      Metabolism and Biochemistry, University of Siena, Siena, ItalyDepartment of 
      Surgery and OncologyUniversity of Verona, Verona, ItalyDivision of 
      SurgicalMolecular and Ultrastructural, Section of Cytopathology, University 
      Hospital of Pisa, Pisa, ItalyNuclear Medicine UnitUniversity Hospital of Verona, 
      Verona, Italy.
FAU - Di Coscio, Giancarlo
AU  - Di Coscio G
AD  - Department of Pathology and DiagnosticsARC-NET Research CentreUniversity of 
      Verona, Policlinico GB Rossi, Piazzale LA Scuro, 10, Piastra Odontoiatrica (II 
      floor), 37134 Verona, ItalyDepartment of Internal MedicineEndocrinology, and 
      Metabolism and Biochemistry, University of Siena, Siena, ItalyDepartment of 
      Surgery and OncologyUniversity of Verona, Verona, ItalyDivision of 
      SurgicalMolecular and Ultrastructural, Section of Cytopathology, University 
      Hospital of Pisa, Pisa, ItalyNuclear Medicine UnitUniversity Hospital of Verona, 
      Verona, Italy.
FAU - Chilosi, Marco
AU  - Chilosi M
AD  - Department of Pathology and DiagnosticsARC-NET Research CentreUniversity of 
      Verona, Policlinico GB Rossi, Piazzale LA Scuro, 10, Piastra Odontoiatrica (II 
      floor), 37134 Verona, ItalyDepartment of Internal MedicineEndocrinology, and 
      Metabolism and Biochemistry, University of Siena, Siena, ItalyDepartment of 
      Surgery and OncologyUniversity of Verona, Verona, ItalyDivision of 
      SurgicalMolecular and Ultrastructural, Section of Cytopathology, University 
      Hospital of Pisa, Pisa, ItalyNuclear Medicine UnitUniversity Hospital of Verona, 
      Verona, Italy.
FAU - Brunelli, Matteo
AU  - Brunelli M
AD  - Department of Pathology and DiagnosticsARC-NET Research CentreUniversity of 
      Verona, Policlinico GB Rossi, Piazzale LA Scuro, 10, Piastra Odontoiatrica (II 
      floor), 37134 Verona, ItalyDepartment of Internal MedicineEndocrinology, and 
      Metabolism and Biochemistry, University of Siena, Siena, ItalyDepartment of 
      Surgery and OncologyUniversity of Verona, Verona, ItalyDivision of 
      SurgicalMolecular and Ultrastructural, Section of Cytopathology, University 
      Hospital of Pisa, Pisa, ItalyNuclear Medicine UnitUniversity Hospital of Verona, 
      Verona, Italy.
FAU - Pacini, Furio
AU  - Pacini F
AD  - Department of Pathology and DiagnosticsARC-NET Research CentreUniversity of 
      Verona, Policlinico GB Rossi, Piazzale LA Scuro, 10, Piastra Odontoiatrica (II 
      floor), 37134 Verona, ItalyDepartment of Internal MedicineEndocrinology, and 
      Metabolism and Biochemistry, University of Siena, Siena, ItalyDepartment of 
      Surgery and OncologyUniversity of Verona, Verona, ItalyDivision of 
      SurgicalMolecular and Ultrastructural, Section of Cytopathology, University 
      Hospital of Pisa, Pisa, ItalyNuclear Medicine UnitUniversity Hospital of Verona, 
      Verona, Italy.
FAU - Ferdeghini, Marco
AU  - Ferdeghini M
AD  - Department of Pathology and DiagnosticsARC-NET Research CentreUniversity of 
      Verona, Policlinico GB Rossi, Piazzale LA Scuro, 10, Piastra Odontoiatrica (II 
      floor), 37134 Verona, ItalyDepartment of Internal MedicineEndocrinology, and 
      Metabolism and Biochemistry, University of Siena, Siena, ItalyDepartment of 
      Surgery and OncologyUniversity of Verona, Verona, ItalyDivision of 
      SurgicalMolecular and Ultrastructural, Section of Cytopathology, University 
      Hospital of Pisa, Pisa, ItalyNuclear Medicine UnitUniversity Hospital of Verona, 
      Verona, Italy Department of Pathology and DiagnosticsARC-NET Research 
      CentreUniversity of Verona, Policlinico GB Rossi, Piazzale LA Scuro, 10, Piastra 
      Odontoiatrica (II floor), 37134 Verona, ItalyDepartment of Internal 
      MedicineEndocrinology, and Metabolism and Biochemistry, University of Siena, 
      Siena, ItalyDepartment of Surgery and OncologyUniversity of Verona, Verona, 
      ItalyDivision of SurgicalMolecular and Ultrastructural, Section of Cytopathology, 
      University Hospital of Pisa, Pisa, ItalyNuclear Medicine UnitUniversity Hospital 
      of Verona, Verona, Italy.
LA  - eng
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150219
PL  - England
TA  - Eur J Endocrinol
JT  - European journal of endocrinology
JID - 9423848
RN  - 0 (MAS1 protein, human)
RN  - 0 (Proto-Oncogene Mas)
RN  - 0 (Reagent Kits, Diagnostic)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-ret)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Carcinoma/*genetics/pathology
MH  - Carcinoma, Papillary
MH  - Child
MH  - Cohort Studies
MH  - Female
MH  - Gene Rearrangement
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/*methods
MH  - Male
MH  - Middle Aged
MH  - Paraffin Embedding
MH  - Polymerase Chain Reaction
MH  - Proto-Oncogene Mas
MH  - Proto-Oncogene Proteins c-ret/*genetics
MH  - Reagent Kits, Diagnostic
MH  - Reference Standards
MH  - Thyroid Cancer, Papillary
MH  - Thyroid Neoplasms/*genetics/pathology
MH  - Tissue Fixation
MH  - Young Adult
EDAT- 2015/02/24 06:00
MHDA- 2015/05/23 06:00
CRDT- 2015/02/21 06:00
PHST- 2015/02/21 06:00 [entrez]
PHST- 2015/02/24 06:00 [pubmed]
PHST- 2015/05/23 06:00 [medline]
AID - EJE-14-0930 [pii]
AID - 10.1530/EJE-14-0930 [doi]
PST - ppublish
SO  - Eur J Endocrinol. 2015 May;172(5):571-82. doi: 10.1530/EJE-14-0930. Epub 2015 Feb 
      19.