High levels of nucleolar expression of nucleolin are associated with better prognosis in patients with stage II pancreatic ductal adenocarcinoma.
OBJECTIVE
Nucleolin is a major nucleolar protein that has been shown to be overexpressed in rapidly dividing cells and plays an essential role in cell proliferation and survival. However, the expression and significance of nucleolin in pancreatic ductal adenocarcinoma (PDA) have not been studied.


METHODS
We used a tissue microarray consisting of 1.0-mm cores of tumor and paired nonneoplastic pancreatic tissue from 69 pancreaticoduodenectomy specimens with stage II PDA. Nucleolin expression was evaluated by immunohistochemistry and scored quantitatively by image analysis. Nucleolin expression was classified as nucleolin-high or nucleolin-low using the median nucleolin labeling index of 3.5% as cutoff. Staining results were correlated with clinicopathologic features and survival.


RESULTS
Both PDAs and PDA cell lines showed nucleolar staining for nucleolin. Nucleolin expression was higher in PDAs and PDA cell lines than in nonneoplastic ductal epithelial cells. Among the 69 stage II PDAs, 34 (49%) were nucleolin-high. The median overall survival was 65.2 +/- 16.3 months for patients who had nucleolin-high PDAs compared with 19.5 +/- 3.3 months for patients whose tumors were nucleolin-low (P = 0.03, log-rank method). No significant correlation between nucleolin expression and other clinicopathologic parameters was found. In multivariate analysis, nucleolin expression was a prognostic factor for overall survival in patients with stage II PDA independent of patient's age, gender, tumor size, differentiation, and lymph node status.


CONCLUSIONS
Nucleolin was overexpressed in PDAs and PDA cell lines. A high level of nucleolar expression of nucleolin was an independent prognostic marker for better survival for patients with stage II PDAs.
Peng
Lan
L
Department of Pathology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA.
Liang
John
J
Wang
Hua
H
Song
Xianzhou
X
Rashid
Asif
A
Gomez
Henry F
HF
Corley
Lynda J
LJ
Abbruzzese
James L
JL
Fleming
Jason B
JB
Evans
Douglas B
DB
Wang
Huamin
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D002466:Cell Nucleolus / Q000378:metabolism*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D010750:Phosphoproteins / Q000096:biosynthesis*; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000096:biosynthesis*; D012189:Retrospective Studies; D046888:Tissue Array Analysis; D014407:Tumor Cells, Cultured; D000097796:Nucleolin
D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D000097796:Nucleolin