Immunohistochemical expression of components of the Akt-mTORC1 pathway is associated with hepatocellular carcinoma in patients with chronic liver disease.
Activation of the Akt-mTORC1 signaling pathway was evaluated in premalignant and hepatocellular carcinoma (HCC) lesions by assessing the expression of pS6, an Akt effector, and PTEN, an Akt suppressor.


METHODS
Immunohistochemical staining for pS6 and PTEN was performed on liver tissue from 52 patients with cirrhosis, with and without HCC. Two pathologists independently evaluated pS6 staining on a semiquantitative scale and categorized PTEN staining as present or absent.


RESULTS
In the HCC group, pS6 staining was greatest in HCC, followed by dysplasia, and benign cirrhotic tissue (P < 0.001). pS6 staining was greater in cirrhotic tissue from patients with HCC compared to cirrhosis in patients without HCC (P = 0.03). PTEN staining in tumor was absent in 8/33 (24%) cases. Loss of PTEN expression was more common in patients with higher tumor stage, compared to those with stage 1 tumors (P = 0.04).


CONCLUSIONS
Immunohistochemical evidence of activation of the Akt-mTORC1 pathway is associated with HCC.
Cotler
Scott J
SJ
Department of Medicine, The University of Illinois at Chicago, Chicago, IL 60612, USA. scotler@uic.edu
Hay
Nissim
N
Xie
Hui
H
Chen
Mei Ling
ML
Xu
Pei Zhang
PZ
Layden
Thomas J
TJ
Guzman
Grace
G
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008103:Liver Cirrhosis / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D008875:Middle Aged; D046912:Multiprotein Complexes; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D011506:Proteins; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D038601:Ribosomal Protein S6 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors / Q000378:metabolism
D046912:Multiprotein Complexes; D011506:Proteins; D038601:Ribosomal Protein S6; D014157:Transcription Factors; D000076222:Mechanistic Target of Rapamycin Complex 1; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase