PMID- 16595592
OWN - NLM
STAT- MEDLINE
DCOM- 20060629
LR  - 20120601
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 91
IP  - 6
DP  - 2006 Jun
TI  - RET/papillary thyroid cancer rearrangement in nonneoplastic thyrocytes: 
      follicular cells of Hashimoto's thyroiditis share low-level recombination events 
      with a subset of papillary carcinoma.
PG  - 2414-23
AB  - CONTEXT: RET/papillary thyroid cancer (PTC) is a marker for papillary thyroid 
      carcinoma, but its specificity has been questioned because of the disputed 
      identification of RET/PTC in Hashimoto's thyroiditis (HT), oncocytic tumors, and 
      other thyroid lesions. OBJECTIVE: The objective of this study was to determine 1) 
      whether RET/PTC occurs in nonneoplastic follicular cells of HT, and 2) its 
      recombination rate in thyroid tumors. DESIGN/PATIENTS: Forty-three samples from 
      31 cases of HT were examined using interphase fluorescence in situ hybridization 
      (FISH) with RET probes spanning the breakpoint region; real-time RT-PCR to 
      quantify RET/PTC1, RET/PTC3, and c-RET transcripts; and RT-PCR after laser 
      capture microdissection to enrich samples for follicular cells. The results were 
      compared with those similarly obtained in 34 papillary carcinomas, eight thyroid 
      oncocytic tumors, and 21 normal thyroids. RESULTS: Normal samples showed no RET 
      rearrangement. Sixty-eight percent (15 of 22) of HT were positive by FISH; in all 
      thyroiditis, signals were localized to rare nonneoplastic follicular cells; 
      low-level RET/PTC was identified in 17% (five of 29) of thyroiditis cases by 
      real-time RT-PCR and in an additional six of 11 real-time negative cases after 
      increasing sensitivity with laser capture microdissection. Low RET/PTC1 levels 
      were detected in 26% (nine of 34) of papillary carcinomas with an expression 
      pattern and proportion of FISH-positive cells similar to those of the 
      thyroiditis. Forty-seven percent (16 of 34) of papillary carcinomas and one 
      oncocytic carcinoma expressed high RET/PTC1 mRNA levels. CONCLUSIONS: Low-level 
      RET/PTC recombination occurs in nonneoplastic follicular cells in HT and in a 
      subset of papillary thyroid carcinomas. RET/PTC expression variability should be 
      taken into account for the molecular diagnosis of thyroid lesions. Overlapping 
      molecular mechanisms may govern early stages of tumor development and 
      inflammation in the thyroid.
FAU - Rhoden, Kerry J
AU  - Rhoden KJ
AD  - Ospedale Bellaria, Via Altura 3, 40139 Bologna, Italy. 
      Giovanni.Tallini@ausl.bo.it
FAU - Unger, Kristian
AU  - Unger K
FAU - Salvatore, Giuliana
AU  - Salvatore G
FAU - Yilmaz, Yesim
AU  - Yilmaz Y
FAU - Vovk, Volodymyr
AU  - Vovk V
FAU - Chiappetta, Gennaro
AU  - Chiappetta G
FAU - Qumsiyeh, Mazin B
AU  - Qumsiyeh MB
FAU - Rothstein, Jay L
AU  - Rothstein JL
FAU - Fusco, Alfredo
AU  - Fusco A
FAU - Santoro, Massimo
AU  - Santoro M
FAU - Zitzelsberger, Horst
AU  - Zitzelsberger H
FAU - Tallini, Giovanni
AU  - Tallini G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060404
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (ret-PTC fusion oncoproteins, human)
SB  - IM
CIN - J Clin Endocrinol Metab. 2006 Jun;91(6):2040-2. PMID: 16757533
MH  - Carcinoma, Papillary/*genetics/pathology
MH  - Cell Line
MH  - *Gene Rearrangement
MH  - Hashimoto Disease/*genetics/pathology
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Interphase
MH  - Oncogene Proteins, Fusion/*genetics
MH  - Protein-Tyrosine Kinases/*genetics
MH  - RNA, Messenger/analysis
MH  - *Recombination, Genetic
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Thyroid Gland/cytology/*metabolism
MH  - Thyroid Neoplasms/*genetics/pathology
EDAT- 2006/04/06 09:00
MHDA- 2006/06/30 09:00
CRDT- 2006/04/06 09:00
PHST- 2006/04/06 09:00 [pubmed]
PHST- 2006/06/30 09:00 [medline]
PHST- 2006/04/06 09:00 [entrez]
AID - jc.2006-0240 [pii]
AID - 10.1210/jc.2006-0240 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2006 Jun;91(6):2414-23. doi: 10.1210/jc.2006-0240. Epub 
      2006 Apr 4.