Nuclear localization of annexin A1 is a prognostic factor in oral squamous cell carcinoma.
OBJECTIVE
To investigate whether annexin A1 (ANXA1) expression is a marker in predicting the prognosis of oral cancer patients.


METHODS
We immunohistochemically examined the expression of ANXA1 in 66 cases of oral epithelial dysplasia (OED) and 115 cases of oral squamous cell carcinoma (OSCC). The results were correlated with the clinicopathological parameters of tumors and overall patient survival.


RESULTS
In normal oral mucosa, ANXA1 staining was predominantly located on the cell membrane. In OED and OSCC specimens, membranous staining decreased, whereas nuclear staining increased. Positive nuclear staining was observed in 9 of 66 (13.64%) OED cases and 63 of 115 (54.8%) OSCCs. Kaplan-Meier curves showed that OSCC patients with ANXA1 nuclear staining had significantly shorter overall lengths of survival (P = 0.00036 by the log-rank test). Multivariate analysis showed that ANXA1 nuclear staining is a significant predictor of poor overall survival. And oral cancer SAS cells treated with hepatocyte growth factor (HGF) can induce ANXA1 protein translocation from cytoplasm to nucleus. Cells pretreated with LY294002 (PI3K inhibitor) almost completely inhibited (88.3% inhibition) HGF-mediated ANXA1 nuclear translocation.


CONCLUSIONS
The nuclear localization of ANXA1 protein is a frequent event and could be used as a prognostic factor in OSCC.
Lin
Chiao-Ying
CY
School of Dentistry and Graduate Institute of Clinical Dentistry, College of Medicine, National Taiwan University, Taipei, Taiwan.
Jeng
Yung-Ming
YM
Chou
Han-Yi
HY
Hsu
Hey-Chi
HC
Yuan
Ray-Hwang
RH
Chiang
Chun-Pin
CP
Kuo
Mark Yen-Ping
MY
D017305:Annexin A1 / Q000378:metabolism*; D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D002867:Chromones / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D005455:Fluorescent Antibody Technique; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000494:pharmacology; D009061:Mouth Mucosa / Q000378:metabolism* / Q000473:pathology; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D009367:Neoplasm Staging; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011379:Prognosis; D021381:Protein Transport; D013347:Subcellular Fractions; D015996:Survival Rate; D013624:Taiwan; D014407:Tumor Cells, Cultured
D017305:Annexin A1; D014408:Biomarkers, Tumor; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D017228:Hepatocyte Growth Factor