PMID- 22498943
OWN - NLM
STAT- MEDLINE
DCOM- 20121025
LR  - 20211203
IS  - 1538-7151 (Electronic)
IS  - 0277-1691 (Linking)
VI  - 31
IP  - 3
DP  - 2012 May
TI  - Aberrant expression of the mammalian target of rapamycin, hypoxia-inducible 
      factor-1alpha, and glucose transporter 1 in the development of ovarian clear-cell 
      adenocarcinoma.
PG  - 254-63
LID - 10.1097/PGP.0b013e318237d66c [doi]
AB  - Ovarian clear-cell adenocarcinoma (CCA) is known to be a type of cancer in humans 
      with a high frequency of expression of the mammalian target of rapamycin (mTOR), 
      hypoxia-inducible factor-1 (HIF-1), and glucose transporter 1 (Glut1). In this 
      study, we aimed to determine how these alterations contribute to tumor 
      development of CCAs. Immunohistochemical expressions of phosphorylated-mTOR 
      (p-mTOR), HIF-1alpha, and Glut1 were analyzed in 36 CCAs and 60 coexistent putative 
      precursor lesions: 19 nonatypical and 16 atypical endometriotic lesions, and 11 
      benign and 14 borderline clear-cell adenofibroma (CCAF) components. Twenty-one 
      cases with solitary endometriosis were also examined. The frequencies of 
      immunopositivity for p-mTOR (in cytoplasm or nucleus), HIF-1alpha (in nucleus), and 
      Glut1 increased in accordance with higher cytological atypia in the putative 
      precursors: 58%, 5%, and 16% in the nonatypical endometriosis; 63%, 37%, and 50% 
      in the atypical endometriosis; 77%, 95%, and 95% in the endometriosis-associated 
      CCAs; 27%, 0%, and 0% in the benign-CCAF components; 64%, 79%, and 43% in the 
      borderline CCAF components; and 71%, 100%, and 93% in the CCAF-associated CCAs, 
      respectively. p-mTOR, HIF-1alpha (in the nucleus), and Glut1 were positive in 10%, 
      5%, and 19% of the solitary endometriosis, respectively. In the putative 
      precursor lesions coexisting with CCA, a strong correlation in the expression 
      between p-mTOR and HIF-1alpha and between HIF-1alpha and Glut1 was identified. 
      Expressions of p-mTOR, HIF-1alpha, and Glut1 have already been evident in the 
      putative precursor lesions of CCA, and these alterations cumulatively occur in 
      the development of ovarian CCA.
FAU - Kato, Masafumi
AU  - Kato M
AD  - Departments of Obstetrics and Gynecology, National Defense Medical College, 
      Tokorozawa, Saitama, Japan.
FAU - Yamamoto, Sohei
AU  - Yamamoto S
FAU - Takano, Masashi
AU  - Takano M
FAU - Matsubara, Osamu
AU  - Matsubara O
FAU - Furuya, Kenichi
AU  - Furuya K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Int J Gynecol Pathol
JT  - International journal of gynecological pathology : official journal of the 
      International Society of Gynecological Pathologists
JID - 8214845
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Glucose Transporter Type 1)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (SLC2A1 protein, human)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adenocarcinoma, Clear Cell/*metabolism/pathology
MH  - Adenofibroma/metabolism/pathology
MH  - Biomarkers, Tumor/metabolism
MH  - Endometriosis/metabolism/pathology
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Glucose Transporter Type 1/*metabolism
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism
MH  - Ovarian Neoplasms/*metabolism/pathology
MH  - Retrospective Studies
MH  - TOR Serine-Threonine Kinases/*metabolism
EDAT- 2012/04/14 06:00
MHDA- 2012/10/26 06:00
CRDT- 2012/04/14 06:00
PHST- 2012/04/14 06:00 [entrez]
PHST- 2012/04/14 06:00 [pubmed]
PHST- 2012/10/26 06:00 [medline]
AID - 10.1097/PGP.0b013e318237d66c [doi]
PST - ppublish
SO  - Int J Gynecol Pathol. 2012 May;31(3):254-63. doi: 10.1097/PGP.0b013e318237d66c.