Chemokine receptor CCR6 expression level and aggressiveness of prostate cancer.
OBJECTIVE
CCR6 is expressed in various tumors and has been implicated in the process of tumor progression and metastasis. Its chemokine ligand, CCL20, is present in different tissues including lymph nodes, but also the normal prostate. This study was performed to investigate a potential relationship between CCR6 and CCL20 expression and features of human prostate cancer (PCA) at time of primary treatment.


METHODS
Immunohistochemistry was used to detect CCR6 and CCL20 expression in archival tissue blocks of 80 PCA cases of various tumor grades and stages. Evaluation was semiquantitatively by visual scoring and quantitatively by digital image analysis (DIA). CCR6 and CCL20 expression was compared with Gleason score, stage, perineural invasion, nodal metastasis, age, and preoperative serum prostate-specific antigen (PSA) level by univariate and multivariate analyses.


RESULTS
Staining intensity of CCR6 in tumor cells varied considerably, with it being: weak in 21 tumors (26.2%), intermediate in 44 (55.0%), and strong in 15 (18.8%), with 3.6-log differences in DIA measurements. CCL20 expression was absent in eight tumors (10.0%), weak in 41 (51.2%), intermediate in 23 (28.8%), and strong in eight (10.0%). CCR6 and CCL20 expression did not correlate. CCR6 expression was associated with T-category (P < 0.0005), Gleason score (P = 0.003), and lymph node metastasis (P = 0.002).


CONCLUSIONS
Expression levels of CCR6 in PCA were associated with clinical and pathologic features of more advanced and aggressive prostate cancer. Thus, CCR6 may directly or indirectly be involved in tumor progression and should be evaluated as novel candidate target molecule for specific treatment interventions.
Ghadjar
Pirus
P
Department of Hematology, Medical Oncology and Transfusion Medicine, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany. pirus.ghadjar@charite.de
Loddenkemper
Christoph
C
Coupland
Sarah Ellen
SE
Stroux
Andrea
A
Noutsias
Michel
M
Thiel
Eckhard
E
Christoph
Frank
F
Miller
Kurt
K
Scheibenbogen
Carmen
C
Keilholz
Ulrich
U
D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D054418:Chemokine CCL20 / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008197:Lymph Node Excision; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D054399:Receptors, CCR6 / Q000235:genetics*
D014408:Biomarkers, Tumor; C108355:CCL20 protein, human; C106311:CCR6 protein, human; D054418:Chemokine CCL20; D054399:Receptors, CCR6; D017430:Prostate-Specific Antigen