Validation of stem cell markers in clinical prostate cancer: α6‐Integrin is predictive for non‐aggressive disease. Issue 5 (27th December 2013)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: Prostate. Volume 74:Issue 5(2014)
• Page Start: 488
• Page End: 496
• Publication Date: 2013-12-27
• Subjects: Prostate -- Diseases -- Periodicals; 616
• DOI: 10.1002/pros.22768
• Languages: English
• ISSNs: 0270-4137

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="pros22768-sec-0001" sec-type="section"> <title>BACKGROUND</title> <p>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.</p> </sec> <sec id="pros22768-sec-0002" sec-type="section"> <title>METHODS</title> <p>We validated immunohistochemical expression of stem cell markers in 481 prostate cancer patients and correlated expression with clinicopathologic parameters.</p> </sec> <sec id="pros22768-sec-0003" sec-type="section"> <title>RESULTS</title> <p>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 (<italic>P</italic> = 0.04). α6‐Integrin expression (<5%) occurred in 28.4% patients, while ≥5% α6‐integrin expression was associated with PSA≤10 ng/ml (<italic>P</italic> = 0.01), Gleason score <7 (<italic>P</italic> < 0.01) and pT2‐disease (<italic>P</italic> = 0.02). α6‐integrin was predictive for biochemical recurrence (<italic>P</italic> < 0.01), local recurrence (<italic>P</italic> = 0.03) and disease specific death (<italic>P</italic> = 0.03). EZH2 expression was generally low with 2.6% of tumors showing ≥1% positive cells. EZH2 was associated with Gleason score ≥7 (<italic>P</italic> = 0.01) and biochemical recurrence (<italic>P</italic> = 0.01). We did not identify expression of CD117, CD133, and OCT3/4 in prostate cancer samples.</p> </sec> <sec id="pros22768-sec-0004" sec-type="section"> <title>CONCLUSIONS</title> <p>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. <italic>Prostate 74:488–496, 2014</italic>. © 2013 Wiley Periodicals, Inc.</p> </sec> </abstract>