PMID- 23477374
OWN - NLM
STAT- MEDLINE
DCOM- 20140430
LR  - 20130925
IS  - 1557-9077 (Electronic)
IS  - 1050-7256 (Linking)
VI  - 23
IP  - 10
DP  - 2013 Oct
TI  - Molecular alterations in partially-encapsulated or well-circumscribed follicular 
      variant of papillary thyroid carcinoma.
PG  - 1256-62
LID - 10.1089/thy.2013.0018 [doi]
AB  - BACKGROUND: Studies have described an encapsulated and an infiltrative form of 
      the follicular variant of papillary thyroid carcinoma (FVPTC). Encapsulated 
      FVPTCs have been reported to have virtually no recurrence risk or metastatic 
      potential and to harbor RAS mutations but not BRAF mutations. In contrast, 
      infiltrative tumors have significant metastatic potential, a risk of recurrence, 
      and a BRAF mutation frequency of approximately 25%. In our experience, a 
      substantial number of FVPTCs are neither fully encapsulated nor infiltrative, but 
      instead are partially encapsulated (PE) or well circumscribed (WC). We have 
      previously reported that PE/WC FVPTCs behave in an indolent fashion similar to 
      encapsulated tumors. The purpose of the current study was to evaluate the 
      molecular alterations in PE/WC FVPTC. METHODS: We identified 28 PE/WC FVPTCs 
      resected consecutively at our institution. Targeted mutation analysis of 41 genes 
      including members of the RAS and RAF families was performed on DNA extracted from 
      formalin-fixed, paraffin-embedded blocks using single-base extension chemistry 
      and mass spectrometry. RESULTS: Lymph node metastases were absent in all cases 
      with sampled lymph nodes, and no patients developed tumor recurrences (median 
      follow-up time, 72.8 months). Overall, 13 cases (46%) harbored RAS mutations, 
      including seven (25%) with NRAS mutations (p.Gln61Arg) and six (21%) with HRAS 
      mutations (five had p.Gln61Arg and one had a p.Gln61Lys substitution). No PE/WC 
      FVPTCs had BRAF mutations. CONCLUSIONS: The results of this study confirm our 
      previous finding that PE/WC FVPTCs pursue an indolent clinical course. 
      Additionally, we found that PE/WC tumors have a similar molecular profile to that 
      of encapsulated FVPTCs with frequent RAS mutations (46%) and no BRAF mutations. 
      These molecular results provide further evidence that PE/WC and encapsulated 
      FVPTCs are biologically similar and should be distinguished from more aggressive 
      infiltrative FVPTCs.
FAU - Howitt, Brooke E
AU  - Howitt BE
AD  - 1 Department of Pathology, Brigham and Women's Hospital , Harvard Medical School, 
      Boston, Massachusetts.
FAU - Jia, Yonghui
AU  - Jia Y
FAU - Sholl, Lynette M
AU  - Sholl LM
FAU - Barletta, Justine A
AU  - Barletta JA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130717
PL  - United States
TA  - Thyroid
JT  - Thyroid : official journal of the American Thyroid Association
JID - 9104317
RN  - 0 (Membrane Proteins)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-raf)
RN  - EC 3.6.1.- (GTP Phosphohydrolases)
RN  - EC 3.6.1.- (NRAS protein, human)
RN  - EC 3.6.5.2 (HRAS protein, human)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Amino Acid Substitution
MH  - Boston
MH  - Carcinoma, Papillary, Follicular/*genetics/metabolism/pathology/surgery
MH  - Cohort Studies
MH  - Female
MH  - Follow-Up Studies
MH  - GTP Phosphohydrolases/*genetics/metabolism
MH  - Genetic Association Studies
MH  - Humans
MH  - Male
MH  - Membrane Proteins/*genetics/metabolism
MH  - Middle Aged
MH  - *Mutation
MH  - Proto-Oncogene Proteins c-raf/genetics/metabolism
MH  - Proto-Oncogene Proteins p21(ras)/*genetics/metabolism
MH  - Retrospective Studies
MH  - Thyroid Gland/metabolism/*pathology/surgery
MH  - Thyroid Neoplasms/*genetics/metabolism/pathology/surgery
MH  - Tumor Burden
MH  - Young Adult
MH  - ras Proteins/genetics/metabolism
EDAT- 2013/03/13 06:00
MHDA- 2014/05/03 06:00
CRDT- 2013/03/13 06:00
PHST- 2013/03/13 06:00 [entrez]
PHST- 2013/03/13 06:00 [pubmed]
PHST- 2014/05/03 06:00 [medline]
AID - 10.1089/thy.2013.0018 [doi]
PST - ppublish
SO  - Thyroid. 2013 Oct;23(10):1256-62. doi: 10.1089/thy.2013.0018. Epub 2013 Jul 17.