Ghadjar Pirus, Loddenkemper Christoph, Coupland Sarah Ellen, Stroux Andrea, Noutsias Michel, Thiel Eckhard, Christoph Frank, Miller Kurt, Scheibenbogen Carmen, Keilholz Ulrich
Department of Hematology, Medical Oncology and Transfusion Medicine, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany.
J Cancer Res Clin Oncol. 2008 Nov;134(11):1181-9. doi: 10.1007/s00432-008-0403-5. Epub 2008 May 9.
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.
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.
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).
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.
CCR6在多种肿瘤中表达,并与肿瘤进展和转移过程有关。其趋化因子配体CCL20存在于包括淋巴结在内的不同组织中,也存在于正常前列腺组织中。本研究旨在探讨CCR6和CCL20表达与人类前列腺癌(PCA)初次治疗时的特征之间的潜在关系。
采用免疫组织化学法检测80例不同肿瘤分级和分期的PCA病例存档组织块中CCR6和CCL20的表达。通过视觉评分进行半定量评估,并通过数字图像分析(DIA)进行定量评估。通过单因素和多因素分析,将CCR6和CCL20表达与Gleason评分、分期、神经周围浸润、淋巴结转移、年龄和术前血清前列腺特异性抗原(PSA)水平进行比较。
肿瘤细胞中CCR6的染色强度差异很大,其中21个肿瘤(26.2%)为弱阳性,44个(55.0%)为中等强度,15个(18.8%)为强阳性,DIA测量值相差3.6个对数。8个肿瘤(10.0%)未检测到CCL20表达,41个(51.2%)为弱阳性,23个(28.8%)为中等强度,8个(10.0%)为强阳性。CCR6和CCL20的表达无相关性。CCR6表达与T分期(P < 0.0005)、Gleason评分(P = 0.003)和淋巴结转移(P = 0.002)相关。
PCA中CCR6的表达水平与更晚期和侵袭性前列腺癌的临床和病理特征相关。因此,CCR6可能直接或间接参与肿瘤进展,应作为特定治疗干预的新型候选靶分子进行评估。