Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands.
Prostate. 2014 May;74(5):488-96. doi: 10.1002/pros.22768. Epub 2013 Dec 27.
Stem cells are postulated to mediate prostate cancer progression, and represent a small fraction of the entire tumor. Various proteins (α2-integrin, α6-integrin, CD117, CD133, EZH2, OCT3/4) are associated with a prostate cancer stem cell phenotype in cell lines and xenografts. Our objective was to investigate expression of stem cell markers in clinical prostate cancer in relation to outcome.
We validated immunohistochemical expression of stem cell markers in 481 prostate cancer patients and correlated expression with clinicopathologic parameters.
Sporadic expression of α2-integrin was present in a fraction of tumor cells (<5%) in 94.7% of tumors and associated with PSA > 10 ng/ml (P = 0.04). α6-Integrin expression (<5%) occurred in 28.4% patients, while ≥5% α6-integrin expression was associated with PSA≤10 ng/ml (P = 0.01), Gleason score <7 (P < 0.01) and pT2-disease (P = 0.02). α6-integrin was predictive for biochemical recurrence (P < 0.01), local recurrence (P = 0.03) and disease specific death (P = 0.03). EZH2 expression was generally low with 2.6% of tumors showing ≥1% positive cells. EZH2 was associated with Gleason score ≥7 (P = 0.01) and biochemical recurrence (P = 0.01). We did not identify expression of CD117, CD133, and OCT3/4 in prostate cancer samples.
Expression of α2-integrin and EZH2 in a small fraction of prostate cancer cells is supportive for their role as stem cell marker. Although α6-integrin was not a unique stem cell marker, it was predictive for prostate cancer biochemical and local recurrence, and disease specific death. The validity of CD117, CD133, and OCT3/4 as prostate cancer stem cell marker is questionable since these proteins were not expressed in clinical prostate cancer.
干细胞被认为介导前列腺癌的进展，并且代表整个肿瘤的一小部分。各种蛋白质（α2-整合素、α6-整合素、CD117、CD133、EZH2、OCT3/4）与细胞系和异种移植物中的前列腺癌干细胞表型相关。我们的目的是研究临床前列腺癌中干细胞标志物的表达与结局的关系。
我们在 481 例前列腺癌患者中验证了干细胞标志物的免疫组织化学表达，并将其表达与临床病理参数相关联。
α2-整合素的散在表达存在于 94.7%的肿瘤中 <5% 的肿瘤细胞中，并与 PSA>10ng/ml 相关（P=0.04）。α6-整合素表达（<5%）发生在 28.4%的患者中，而≥5%的α6-整合素表达与 PSA≤10ng/ml（P=0.01）、Gleason 评分<7（P<0.01）和 pT2 疾病（P=0.02）相关。α6-整合素对生化复发有预测作用（P<0.01），对局部复发（P=0.03）和疾病特异性死亡（P=0.03）有预测作用。EZH2 的表达通常较低，有 2.6%的肿瘤显示≥1%的阳性细胞。EZH2与 Gleason 评分≥7（P=0.01）和生化复发（P=0.01）相关。我们没有在前列腺癌样本中发现 CD117、CD133 和 OCT3/4 的表达。
在一小部分前列腺癌细胞中表达 α2-整合素和 EZH2 支持它们作为干细胞标志物的作用。尽管α6-整合素不是一个独特的干细胞标志物，但它对前列腺癌的生化和局部复发以及疾病特异性死亡有预测作用。CD117、CD133 和 OCT3/4 作为前列腺癌干细胞标志物的有效性是值得怀疑的，因为这些蛋白在临床前列腺癌中没有表达。
