Positive expression of L1-CAM is associated with perineural invasion and poor outcome in pancreatic ductal adenocarcinoma.
BACKGROUND
Pancreatic ductal adenocarcinoma (PDAC) frequently invades and migrates along neural tissue, which results in local tumor recurrences, distant metastases, and poor prognosis. We evaluated whether L1 cell adhesion molecule (L1-CAM) and glial cell line-derived neurotrophic factor (GDNF) expression in PDAC correlated with neural invasion and overall survival on a large cohort of previously untreated patients.


METHODS
L1-CAM and GDNF were examined by immunohistochemistry in pancreatic cancer tissue samples of 94 cases with PDAC on a tissue microarray. The molecular findings were correlated with pain, clinicopathologic characteristics, and overall survival in these patients.


RESULTS
L1-CAM and GDNF were overexpressed in pancreatic cancer tissues compared with the adjacent normal tissues of pancreas. Positive L1-CAM expression was associated with node involvement (P = 0.007), vascular invasion (P = 0.012), perineural invasion (P = 0.001), and higher degree of pain (P = 0.005). In univariate analysis, tissue expression of L1-CAM was associated with poor survival (hazard ratio, 2.508; 95% confidence interval, 1.551-4.053; P < 0.001), and this was also significant in multivariate analysis (hazard ratio, 2.046; 95% confidence interval, 1.200-3.488; P = 0.009). Positive staining of GDNF, neural invasion, and vascular invasion were all statistically significantly related to unfavorable prognosis.


CONCLUSIONS
Enhanced expression of L1-CAM may contribute to the pain syndrome and perineural invasion and may correlate with poor overall survival in human pancreatic cancer.
Ben
Qi-Wen
QW
Department of Gastroenterology, School of Medicine, Ruijin Hospital, Shanghai Jiaotong University, Shanghai, People's Republic of China.
Wang
Jian-Cheng
JC
Liu
Jun
J
Zhu
Ying
Y
Yuan
Fei
F
Yao
Wei-Yan
WY
Yuan
Yao-Zong
YZ
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism*; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism*; D010147:Pain Measurement; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D010525:Peripheral Nerves / Q000473:pathology*; D011379:Prognosis; D015996:Survival Rate
D051100:Glial Cell Line-Derived Neurotrophic Factor; D009363:Neoplasm Proteins; D039842:Neural Cell Adhesion Molecule L1