PMID- 30556200
OWN - NLM
STAT- MEDLINE
DCOM- 20201007
LR  - 20211204
IS  - 1097-0347 (Electronic)
IS  - 1043-3074 (Print)
IS  - 1043-3074 (Linking)
VI  - 41
IP  - 3
DP  - 2019 Mar
TI  - PI3-kinase pathway biomarkers in oral cancer and tumor immune cells.
PG  - 615-622
LID - 10.1002/hed.25350 [doi]
AB  - BACKGROUND: This study investigated the hypothesis that phosphoinositide 3-kinase 
      (PI3-kinase) pathway dysregulation in either head and neck cancer cells and/or 
      tumor infiltrating immune cells would influence outcomes of patients with 
      surgically treated oral tongue squamous cell carcinomas (SCC). METHODS: We 
      constructed tissue microarrays containing 123 oral tongue SCC samples and 
      performed immunohistochemistry using antibodies against 7 PI3-kinase pathway 
      markers: phosphatase and tensin homolog (PTEN), Akt, p-Akt, mammalian target of 
      rapamycin (mTOR), phosphorylated-mammalian target of rapamycin (p-mTOR), 
      survivin, and Ki-67). Expression levels in cancer cells or tumor infiltrating 
      immune cells were correlated with outcomes. RESULTS: Higher levels of PTEN 
      expression in immune cells were significantly associated with improved 
      recurrence-free survival (heart rate (HR) = 0.45, 95% confidence interval (CI) 
      0.23-0.90, P = .03), and overall survival (HR = 0.34, 95% CI 0.15-0.76, P = .01) 
      on univariate and multicovariate models. CONCLUSIONS: We identified a novel, 
      negative prognostic role of PI3-kinase activation (as determined by PTEN loss) in 
      oral SCC infiltrating immune cells. These findings could be relevant for clinical 
      development of PI-3 kinase inhibitors for this disease.
CI  - (c) 2018 Wiley Periodicals, Inc.
FAU - Ibrahim, Mohammad Y
AU  - Ibrahim MY
AD  - Seton Hall University College of Arts and Sciences, Department of Internal 
      Medicine at St. Francis Medical Center.
FAU - Nunez, Maria I
AU  - Nunez MI
AD  - The University of Texas MD Anderson Cancer Center, Department of Pathology.
FAU - Harun, Nusrat
AU  - Harun N
AD  - The University of Texas MD Anderson Cancer Center, Department of Biostatistics.
FAU - Lee, J Jack
AU  - Lee JJ
AD  - The University of Texas MD Anderson Cancer Center, Department of Biostatistics.
FAU - El-Naggar, Adel K
AU  - El-Naggar AK
AD  - The University of Texas MD Anderson Cancer Center, Department of Pathology.
FAU - Ferrarotto, Renata
AU  - Ferrarotto R
AD  - The University of Texas MD Anderson Cancer Center, Department of Thoracic/Head 
      and Neck Medical Oncology.
FAU - Wistuba, Ignacio
AU  - Wistuba I
AD  - The University of Texas MD Anderson Cancer Center, Department of Pathology.
AD  - The University of Texas MD Anderson Cancer Center, Department of Translational 
      Molecular Pathology.
FAU - Myers, Jeffrey
AU  - Myers J
AD  - The University of Texas MD Anderson Cancer Center, Head and Neck Surgery, 
      Houston, TX.
FAU - Glisson, Bonnie S
AU  - Glisson BS
AD  - The University of Texas MD Anderson Cancer Center, Department of Thoracic/Head 
      and Neck Medical Oncology.
FAU - William, William N Jr
AU  - William WN Jr
AD  - The University of Texas MD Anderson Cancer Center, Department of Thoracic/Head 
      and Neck Medical Oncology.
LA  - eng
GR  - P30 CA016672/CA/NCI NIH HHS/United States
GR  - P50 CA070907/CA/NCI NIH HHS/United States
GR  - P50 CA097007/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20181216
PL  - United States
TA  - Head Neck
JT  - Head & neck
JID - 8902541
RN  - 0 (BIRC5 protein, human)
RN  - 0 (Biomarkers)
RN  - 0 (Survivin)
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 (TOR Serine-Threonine Kinases)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (PTEN protein, human)
SB  - IM
MH  - Biomarkers/metabolism
MH  - Carcinoma, Squamous Cell/*metabolism/mortality/pathology
MH  - Female
MH  - Humans
MH  - Lymphocytes/metabolism
MH  - Macrophages/metabolism
MH  - Male
MH  - Middle Aged
MH  - PTEN Phosphohydrolase/*metabolism
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Retrospective Studies
MH  - Signal Transduction/*physiology
MH  - Survival Rate
MH  - Survivin/metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Tongue Neoplasms/*metabolism/mortality/pathology
PMC - PMC6382518
MID - NIHMS969679
OTO - NOTNLM
OT  - immunology
OT  - oral squamous cell carcinomas
OT  - phosphatase and tensin homolog (PTEN)
OT  - phosphoinositide 3-kinase pathway (PI3-kinase pathway)
OT  - tumor infiltrating immune cells
COIS- Conflict of interest statement Dr. William N. William Jr. has received honoraria 
      from AstraZeneca, Roche, and Genentech not related to this work, and has received 
      research grants from Eli Lilly, Bristol Myers Squibb, Merck, Astellas 
      Pharmaceuticals, and Boehringer Ingelheim. All other authors do not have 
      conflicts of interest to disclose.
EDAT- 2018/12/18 06:00
MHDA- 2020/10/08 06:00
PMCR- 2020/03/01
CRDT- 2018/12/18 06:00
PHST- 2018/02/20 00:00 [received]
PHST- 2018/03/26 00:00 [revised]
PHST- 2018/05/16 00:00 [accepted]
PHST- 2018/12/18 06:00 [pubmed]
PHST- 2020/10/08 06:00 [medline]
PHST- 2018/12/18 06:00 [entrez]
PHST- 2020/03/01 00:00 [pmc-release]
AID - 10.1002/hed.25350 [doi]
PST - ppublish
SO  - Head Neck. 2019 Mar;41(3):615-622. doi: 10.1002/hed.25350. Epub 2018 Dec 16.