High levels of expression of human stromal cell-derived factor-1 are associated with worse prognosis in patients with stage II pancreatic ductal adenocarcinoma. Cancer Epidemiol Biomarkers Prev 2010 Oct;19(10):2598-604
Date
08/25/2010Pubmed ID
20732965DOI
10.1158/1055-9965.EPI-10-0405Scopus ID
2-s2.0-77958025191 (requires institutional sign-in at Scopus site) 57 CitationsAbstract
BACKGROUND: Stromal cell-derived factor-1 (SDF-1) and its receptor, CXCR4, have been shown to mediate invasiveness and metastatic behavior in a number of cancers, including ovarian, prostate, bladder, breast, and pancreatic cancers. The expression and significance of SDF-1 in pancreatic ductal adenocarcinoma (PDA) have not been systematically studied.
METHODS: We examined the expression of SDF-1 by immunohistochemistry using a mouse anti-human SDF-1/CXCL12 antibody (dilution 1:300) and a tissue microarray consisting of 72 stage II PDAs from pancreaticoduodenectomy specimens. The staining results were categorized as SDF-1-high (SDF-1-H; cytoplasmic staining of ≥10% of tumor cells) or SDF-1-low (SDF-1-L; no staining or staining of <10% of tumor cells). The results of SDF-1 expression were correlated with clinicopathologic parameters and survival. Statistical analyses were done using SPSS software.
RESULT: Of the 72 stage II PDAs, 25 (35%) showed high levels of SDF-1 expression. The median overall and recurrence-free survival for patients with SDF-1-H PDAs were 26.1 and 11.1 months, respectively, compared with 44.3 and 22.3 months for patients with SDF-1-L tumors (log-rank test, P = 0.047 and P = 0.021). In multivariate analysis, high SDF-1 expression correlated with poor overall and disease-free survival (P = 0.02 and P = 0.02) independent of tumor size, differentiation, and lymph node status.
CONCLUSION: High levels of SDF-1 expression were associated with poor overall and disease-free survival in patients with stage II PDA. SDF-1 may serve as a useful prognostic marker for stage II PDA.
IMPACT: Our results suggest that SDF-1-CXCR4 or SDF-1-CXCR7 pathways may represent a potential target for therapeutic intervention as well as prediction of prognosis in PDA.
Author List
Liang JJ, Zhu S, Bruggeman R, Zaino RJ, Evans DB, Fleming JB, Gomez HF, Zander DS, Wang HAuthor
Douglas B. Evans MD Chair, Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultAged
Aged, 80 and over
Animals
Biomarkers, Tumor
Carcinoma, Pancreatic Ductal
Chemokine CXCL12
Disease-Free Survival
Female
Humans
Immunohistochemistry
Male
Mice
Middle Aged
Neoplasm Staging
Pancreatic Neoplasms
Prognosis