High expression of CXCR4 may predict poor survival in resected pancreatic adenocarcinoma.
Chemokines and their receptors are involved in tumourigenicity and clinicopathological significance of chemokines receptor expression in pancreatic adenocarcinoma (PA) is not fully understood. This study was conducted to determine patients' outcome according to the expressions of CXCR4, CXCR7 and HIF-1alpha after resection of PA. Immunohistochemistry for CXCR4, CXCR7 and HIF-1alpha expressions as well as cell proliferative index (Ki-67) was conducted in 71 resected (R0) PA and their 48 related lymph nodes (LN) using tissue microarray. CXCR4 and CXCR7 expressions were positively correlated to HIF-1alpha suggesting a potential role of HIF-1alpha in CXCR4 and CXCR7 transcription activation. Patients with CXCR4(high) tumour expression had shorter OS than those with low expression (median survival: 9.7 vs 43.2 months, P=0.0006), a higher risk of LN metastases and liver recurrence. In multivariate analysis, high CXCR4 expression, LN metastases and poorly differentiated tumour are independent negative prognosis factors. In a combining analysis, patients with a CXCR7(high)/CXCR4(high) [corrected] tumour had a significantly shorter DFS and OS than patients with a CXCR4(low)/CXCR7(low) [corrected] tumour. CXCR4 in resected PA may represent a valuable prognostic factor as well as an attractive target for therapeutic purpose.
Maréchal
R
R
Department of Gastroenterology, GI cancer Unit, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium. rmarecha@ulb.ac.be
Demetter
P
P
Nagy
N
N
Berton
A
A
Decaestecker
C
C
Polus
M
M
Closset
J
J
Devière
J
J
Salmon
I
I
Van Laethem
J-L
JL
D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D010180:Pancreatectomy / Q000401:mortality / Q000706:statistics & numerical data*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D011379:Prognosis; D054387:Receptors, CXCR / Q000235:genetics; D019718:Receptors, CXCR4 / Q000235:genetics*; D012189:Retrospective Studies; D016019:Survival Analysis; D017741:Survivors
C501896:ACKR3 protein, human; C527276:CXCR4 protein, human; D054387:Receptors, CXCR; D019718:Receptors, CXCR4