PMID- 21113138
OWN - NLM
STAT- MEDLINE
DCOM- 20110609
LR  - 20230210
IS  - 1530-0285 (Electronic)
IS  - 0893-3952 (Linking)
VI  - 24
IP  - 3
DP  - 2011 Mar
TI  - PI3K signaling pathway is activated by PIK3CA mRNA overexpression and copy gain 
      in prostate tumors, but PIK3CA, BRAF, KRAS and AKT1 mutations are infrequent 
      events.
PG  - 443-52
LID - 10.1038/modpathol.2010.208 [doi]
AB  - The phosphatidylinositol 3-kinase (PI3K)-AKT and RAS-MAPK pathways are 
      deregulated in a wide range of human cancers by gain or loss of function in 
      several of their components. Our purpose has been to identify genetic alterations 
      in members of these pathways in prostate cancer. A total of 102 prostate tumors, 
      79 from prostate cancer alone (group G1) and 23 from bladder and prostate cancer 
      patients (G2), are the subject of this study. In 20 of these 23, the bladder 
      tumors were also analyzed. PIK3CA, KRAS, BRAF and AKT1 mutations were analyzed by 
      direct sequencing, and BRAF also by pyrosequencing. PIK3CA quantitative mRNA 
      expression and fluorescence in situ hybridization (FISH) gains were tested in 25 
      and 32 prostate tumors from both groups (G1 and G2), respectively. 
      Immunohistochemistry for pAKT was performed in 55 prostate tumors. Of 25 prostate 
      tumors, 10 (40%) had PIK3CA mRNA overexpression that was statistically associated 
      with Gleason score >/= 7 (P=0.018). PIK3CA copy gain was detected in 9 of 32 (28%) 
      prostate tumors. Of 20 bladder tumors, 3 (15%) displayed mutations in PIK3CA, 
      KRAS and AKT1, the corresponding prostate tumors being wt. We also detected a 
      previously not reported PIK3CA polymorphism (IVS9+91) in two prostate tumors. In 
      all, 56% of prostate tumors overexpressed pAKT. There is a statistical 
      association (P<0.0001) of strong pAKT immunostaining with high Gleason score, and 
      with PIK3CA alterations (mRNA overexpression and/or FISH gains). PIK3CA gene is 
      deregulated by mRNA overexpression and DNA gain in  approximately  40 and 28% of prostate 
      tumors, respectively. High-grade prostate tumors are associated with PIK3CA mRNA 
      overexpression, but not with FISH status. PIK3CA, BRAF, KRAS and AKT1 mutations 
      are very infrequent events in prostate tumors. However, PI3K signaling pathway is 
      activated by PIK3CA FISH gain and/or mRNA overexpression, leading to an increased 
      pAKT protein expression.
FAU - Agell, Laia
AU  - Agell L
AD  - Department of Pathology, Hospital del Mar-Parc de Salut Mar, Barcelona, Spain.
FAU - Hernandez, Silvia
AU  - Hernandez S
FAU - Salido, Marta
AU  - Salido M
FAU - de Muga, Silvia
AU  - de Muga S
FAU - Juanpere, Nuria
AU  - Juanpere N
FAU - Arumi-Uria, Montserrat
AU  - Arumi-Uria M
FAU - Menendez, Silvia
AU  - Menendez S
FAU - Lorenzo, Marta
AU  - Lorenzo M
FAU - Lorente, Jose A
AU  - Lorente JA
FAU - Serrano, Sergio
AU  - Serrano S
FAU - Lloreta, Josep
AU  - Lloreta J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101126
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 (Adaptor Proteins, Signal Transducing)
RN  - 0 (KRAS protein, human)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.1.137 (Class I Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.1.137 (PIK3CA protein, human)
RN  - EC 2.7.11.1 (AKT1 protein, human)
RN  - EC 2.7.11.1 (BRAF protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Adenocarcinoma/*genetics/metabolism/pathology
MH  - Class I Phosphatidylinositol 3-Kinases
MH  - DNA Copy Number Variations
MH  - DNA Mutational Analysis
MH  - *Gene Expression
MH  - Humans
MH  - Male
MH  - *Mutation
MH  - Neoplasm Proteins/*genetics
MH  - Phosphatidylinositol 3-Kinases/*genetics
MH  - Prostatic Neoplasms/*genetics/metabolism/pathology
MH  - Proto-Oncogene Proteins/genetics
MH  - Proto-Oncogene Proteins B-raf/genetics
MH  - Proto-Oncogene Proteins c-akt/genetics
MH  - Proto-Oncogene Proteins p21(ras)
MH  - RNA, Messenger/*genetics
MH  - Signal Transduction
MH  - ras Proteins/genetics
EDAT- 2010/11/30 06:00
MHDA- 2011/06/10 06:00
CRDT- 2010/11/30 06:00
PHST- 2010/11/30 06:00 [entrez]
PHST- 2010/11/30 06:00 [pubmed]
PHST- 2011/06/10 06:00 [medline]
AID - S0893-3952(22)02907-6 [pii]
AID - 10.1038/modpathol.2010.208 [doi]
PST - ppublish
SO  - Mod Pathol. 2011 Mar;24(3):443-52. doi: 10.1038/modpathol.2010.208. Epub 2010 Nov 
      26.