PMID- 28945300
OWN - NLM
STAT- MEDLINE
DCOM- 20180720
LR  - 20220410
IS  - 1097-0347 (Electronic)
IS  - 1043-3074 (Linking)
VI  - 39
IP  - 12
DP  - 2017 Dec
TI  - Upregulation of pAKT(Ser473) expression in progression of HPV-positive 
      oropharyngeal squamous cell carcinoma.
PG  - 2397-2405
LID - 10.1002/hed.24910 [doi]
AB  - BACKGROUND: PIK3CA alterations have been shown to be a frequent event in 
      oropharyngeal squamous cell cancer (SCC), especially in human papillomavirus 
      (HPV)-related tumors. METHODS: Tissue microarrays (TMAs) were used to evaluate 
      pAKT(Ser473)/(Thr308), total protein kinase B (AKT)(pan) and phosphatase and 
      tensin homolog (PTEN) expression in primary tumors and corresponding nodal 
      disease in oropharyngeal SCC. The HPV status was determined in regard of HPV16 
      DNA and RNA. Survival analysis was performed by using Kaplan-Meier curves, 
      log-rank testing, and multivariate Cox regression analysis. RESULTS: HPV16 is a 
      prognostic predictive marker for advanced oropharyngeal SCC. pAKT(Ser473) and 
      PTEN are highly expressed in HPV-related oropharyngeal SCCs in contrast to 
      pAKT(Thr308). The pAKT(Ser473) expression increased from primary tumors to 
      progressive nodal disease (21.1%; P < .011). CONCLUSION: Activation of 
      phosphoinositide 3-kinase (PI3K)/pAKT(Ser473) frequently occurs in advanced 
      HPV-positive oropharyngeal SCC and elevated pAKT(Ser473) levels represent a 
      feature during progression of oropharyngeal SCC, indicating a critical role of 
      the mammalian target of rapamycin (mTOR) complex. Further studies are required to 
      evaluate specific drugs targeting PI3K/AKT/mTOR in consideration of PIK3CA 
      alterations.
CI  - (c) 2017 Wiley Periodicals, Inc.
FAU - Horn, Dominik
AU  - Horn D
AUID- ORCID: 0000-0001-5017-0815
AD  - Department of Oral and Cranio-Maxillofacial Surgery, Heidelberg University 
      Hospital, Heidelberg, Germany.
FAU - Freudlsperger, Christian
AU  - Freudlsperger C
AD  - Department of Oral and Cranio-Maxillofacial Surgery, Heidelberg University 
      Hospital, Heidelberg, Germany.
FAU - Holzinger, Dana
AU  - Holzinger D
AD  - Molecular Diagnostics of Oncogenic Infections, German Cancer Research Center 
      (DKFZ), Heidelberg, Germany.
FAU - Kunzmann, Kevin
AU  - Kunzmann K
AD  - Institute for Medical Biometry and Informatics, Heidelberg University Hospital, 
      Heidelberg, Germany.
FAU - Plinkert, Peter
AU  - Plinkert P
AD  - Department of Otorhinolaryngology, Head and Neck Surgery, Heidelberg University 
      Hospital, Heidelberg, Germany.
FAU - Dyckhoff, Gerhard
AU  - Dyckhoff G
AD  - Department of Otorhinolaryngology, Head and Neck Surgery, Heidelberg University 
      Hospital, Heidelberg, Germany.
FAU - Hoffmann, Jurgen
AU  - Hoffmann J
AD  - Department of Oral and Cranio-Maxillofacial Surgery, Heidelberg University 
      Hospital, Heidelberg, Germany.
FAU - Freier, Kolja
AU  - Freier K
AD  - Department of Oral and Cranio-Maxillofacial Surgery, Heidelberg University 
      Hospital, Heidelberg, Germany.
FAU - Hess, Jochen
AU  - Hess J
AD  - Department of Otorhinolaryngology, Head and Neck Surgery, Heidelberg University 
      Hospital, Heidelberg, Germany.
AD  - Research Group Molecular Mechanisms of Head and Neck Tumors, German Cancer 
      Research Center (DKFZ), Heidelberg, Germany.
LA  - eng
PT  - Journal Article
DEP - 20170925
PL  - United States
TA  - Head Neck
JT  - Head & neck
JID - 8902541
RN  - EC 2.7.1.137 (Class I Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.1.137 (PIK3CA protein, human)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (PTEN protein, human)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Analysis of Variance
MH  - Biopsy, Needle
MH  - Carcinoma, Squamous Cell/*genetics/pathology/surgery/virology
MH  - Class I Phosphatidylinositol 3-Kinases/*genetics
MH  - Cohort Studies
MH  - Disease Progression
MH  - Disease-Free Survival
MH  - Female
MH  - *Gene Expression Regulation, Neoplastic
MH  - Head and Neck Neoplasms/*genetics/pathology/surgery/virology
MH  - Humans
MH  - Immunohistochemistry
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Middle Aged
MH  - Multivariate Analysis
MH  - Oropharyngeal Neoplasms/*genetics/pathology/surgery/virology
MH  - PTEN Phosphohydrolase/*genetics
MH  - Papillomavirus Infections/*complications/mortality
MH  - Prognosis
MH  - Retrospective Studies
MH  - Risk Assessment
MH  - Squamous Cell Carcinoma of Head and Neck
MH  - Survival Analysis
MH  - Up-Regulation
OTO - NOTNLM
OT  - human papillomavirus
OT  - lymph node metastasis
OT  - oropharyngeal squamous cell carcinoma
OT  - protein kinase B (AKT)
OT  - tissue microarray
EDAT- 2017/09/26 06:00
MHDA- 2018/07/22 06:00
CRDT- 2017/09/26 06:00
PHST- 2016/12/04 00:00 [received]
PHST- 2017/06/06 00:00 [revised]
PHST- 2017/07/06 00:00 [accepted]
PHST- 2017/09/26 06:00 [pubmed]
PHST- 2018/07/22 06:00 [medline]
PHST- 2017/09/26 06:00 [entrez]
AID - 10.1002/hed.24910 [doi]
PST - ppublish
SO  - Head Neck. 2017 Dec;39(12):2397-2405. doi: 10.1002/hed.24910. Epub 2017 Sep 25.