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Validation of stem cell markers in clinical prostate cancer: α6‐Integrin is predictive for non‐aggressive disease
Author(s) -
Hoogland A. Marije,
Verhoef Esther I.,
Roobol Monique J.,
Schröder Fritz H.,
Wildhagen Mark F.,
van der Kwast Theo H.,
Jenster Guido,
van Leenders Geert J.L.H.
Publication year - 2014
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.22768
Subject(s) - prostate cancer , cancer stem cell , stem cell marker , medicine , pca3 , stem cell , cd117 , pathology , prostate , oncology , predictive marker , cancer research , cancer , biology , cd34 , genetics
BACKGROUND 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. METHODS We validated immunohistochemical expression of stem cell markers in 481 prostate cancer patients and correlated expression with clinicopathologic parameters. RESULTS 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. CONCLUSIONS 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. Prostate 74:488–496, 2014 . © 2013 Wiley Periodicals, Inc.