PMID- 21822208
OWN - NLM
STAT- MEDLINE
DCOM- 20120328
LR  - 20230210
IS  - 1530-0285 (Electronic)
IS  - 0893-3952 (Linking)
VI  - 24
IP  - 12
DP  - 2011 Dec
TI  - Morphoproteomics demonstrates activation of mammalian target of rapamycin pathway 
      in papillary thyroid carcinomas with nuclear translocation of MTOR in aggressive 
      histological variants.
PG  - 1553-9
LID - 10.1038/modpathol.2011.121 [doi]
AB  - We used morphoproteomics to investigate mammalian target of rapamycin (MTOR) 
      signaling pathway in papillary thyroid carcinomas and correlated the results with 
      clinicopathological parameters. Archival paraffin-embedded tissue of papillary 
      thyroid carcinomas was obtained from 30 patients, including 15 classical type and 
      8 follicular, 4 tall-cell, 1 columnar-cell, 1 diffuse sclerosing and 1 cribriform 
      variants. Immunohistochemical stains were performed for three phosphorylated (p) 
      protein analytes: p-MTOR (Ser2448), p-Akt (Ser473) and p-p70S6K (Thr389). 
      Chromogenic signals and subcellular compartmentalization (nuclear, cytoplasmic 
      and plasmalemmal) were evaluated. Clinicopathological parameters were reviewed. 
      Immunoreactivities for p-MTOR, p-Akt and p-p70S6K were observed in all papillary 
      thyroid carcinomas. In addition to an expression of p-MTOR in cytoplasmic 
      location, nuclear translocation of p-MTOR with variable loss of plasmalemmal 
      expression, and with concomitant nuclear expression of p-Akt, was also identified 
      in all tall-cell, columnar-cell and diffuse sclerosing variants of papillary 
      thyroid carcinoma. There were no significant differences in the 
      clinicopathological parameters, including tumor size, extrathyroidal extension, 
      angioinvasion and nodal metastases between the groups with and without nuclear 
      expression of p-MTOR (P>0.05). The expressions of p-MTOR in cytoplasmic and/or 
      plasmalemmal locations with the concomitant immunoreactivity for p-p70S6K in all 
      papillary thyroid carcinomas indicate the activation of MTOR complex 1 pathway. 
      The nuclear translocation of p-MTOR evidences the activation of MTOR complex 2 
      and is identified only in the known aggressive histological variants of papillary 
      thyroid carcinoma, including tall-cell, columnar-cell and diffuse sclerosing 
      variants. Thus, these results suggest the constitutive activation of MTOR 
      signaling pathway in papillary thyroid carcinomas and provide a new insight of 
      biogenetic basis for the aggressive histological variants of papillary thyroid 
      carcinoma. The pattern of expression of p-MTOR in papillary thyroid carcinomas 
      may serve as a diagnostic/prognostic marker and a potential therapeutic target.
FAU - Liu, Jing
AU  - Liu J
AD  - Department of Pathology and Laboratory Medicine, University of Texas Health 
      Science Center at Houston Medical School, Houston, TX, USA. 
      jing.liu.1@uth.tmc.edu
FAU - Brown, Robert E
AU  - Brown RE
LA  - eng
PT  - Journal Article
DEP - 20110805
PL  - United States
TA  - Mod Pathol
JT  - Modern pathology : an official journal of the United States and Canadian Academy 
      of Pathology, Inc
JID - 8806605
RN  - 0 (Biomarkers, Tumor)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Active Transport, Cell Nucleus
MH  - Biomarkers, Tumor/*analysis
MH  - Carcinoma
MH  - Carcinoma, Papillary
MH  - Cell Nucleus/*enzymology/pathology
MH  - Enzyme Activation
MH  - Humans
MH  - Immunohistochemistry
MH  - Lymphatic Metastasis
MH  - Neoplasm Invasiveness
MH  - Phosphorylation
MH  - Prognosis
MH  - *Proteomics/methods
MH  - Proto-Oncogene Proteins c-akt/analysis
MH  - Ribosomal Protein S6 Kinases, 70-kDa/analysis
MH  - *Signal Transduction
MH  - TOR Serine-Threonine Kinases/*analysis
MH  - Thyroid Cancer, Papillary
MH  - Thyroid Neoplasms/*enzymology/secondary
MH  - Tumor Burden
EDAT- 2011/08/09 06:00
MHDA- 2012/03/29 06:00
CRDT- 2011/08/09 06:00
PHST- 2011/08/09 06:00 [entrez]
PHST- 2011/08/09 06:00 [pubmed]
PHST- 2012/03/29 06:00 [medline]
AID - S0893-3952(22)03102-7 [pii]
AID - 10.1038/modpathol.2011.121 [doi]
PST - ppublish
SO  - Mod Pathol. 2011 Dec;24(12):1553-9. doi: 10.1038/modpathol.2011.121. Epub 2011 
      Aug 5.