The role of vascular CXCR4 expression in colorectal carcinoma.
OBJECTIVE
The chemokine receptor CXCR4 plays a prominent role in the biology of many different tumours, promoting angiogenesis and metastasis. The impact of CXCR4 expression on tumour biology has been described in various gastrointestinal malignancies, but data on its in situ expression and clinicopathological correlations are sparse. Using a novel specific rabbit anti-CXCR4 antibody, the aim was to assess CXCR4 expression immunohistochemically on tissue microarrays generated from 402 colorectal cancers (CRCs) and compare it with CXCL12 expression and various clinicopathological parameters.


RESULTS
CXCR4-expressing tumour cells were observed in 31% of the cases, and expression correlated only with blood vessel invasion (P = 0.049). Furthermore, CXCR4 was found in tumour microvessels in 25% of CRCs. This pattern of CXCR4 expression correlated significantly with T- (P = 0.008), N- (P = 0.009), M- (P = 0.043), L- (P = 0.014) and V-category (P = 0.043) as well as with International Union Against Cancer (UICC) stage (P = 0.001). Furthermore, in node negative CRCs, vascular CXCR4 expression was an independent adverse prognostic factor [hazard ratio 2.87 (1.31-6.29), P = 0.009]. No correlation with CXCL12 expression was found.


CONCLUSIONS
Our data provide evidence that CXCR4 plays an important role in tumour angiogenesis of CRC. Therefore, the CXCR4 pathway is a promising therapeutic target for anti-angiogenic therapies in CRC.
Ingold
Barbara
B
Institute of Pathology Campus Mitte, Charité University Hospital, Berlin, Germany. barbara.ingold-heppner@charite.de
Schulz
Stefan
S
Budczies
Jan
J
Neumann
Ulf
U
Ebert
Matthias P A
MP
Weichert
Wilko
W
Röcken
Christoph
C
D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D054377:Chemokine CXCL12 / Q000096:biosynthesis; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D019718:Receptors, CXCR4 / Q000096:biosynthesis*; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4