Expression analysis of putative stem cell markers in human benign and malignant prostate.
BACKGROUND
Stem cells were suggested to be present in human prostate cancer as a small population of distinct cells, which may contribute to carcinogenesis, tumor recurrence, and chemoresistance. To identify potential prostatic stem cells, we analyzed the expression of several potential stem cell markers in benign prostate and prostatic adenocarcinoma.


METHODS
CD44, CD133, Oct4, SOX2, and EZH2 expression was detected by immunohistochemical (IHC) staining using tissue microarray assays (TMA) composed of benign (non-neoplastic) prostatic tissue, high grade prostatic intraepithelial neoplasia (HGPIN), and prostatic adenocarcinoma. Positive staining was defined as 1+ (<10%), 2+ (10-50%), or 3+ (>50%).


RESULTS
We found CD44 staining in 97% and 72% of benign + HGPIN and malignant lesions, respectively. CD133 staining was detected in a small fraction (4 of 67) of prostate carcinomas. We found that Oct4 nuclear expression was strongly associated with benign lesions and HGPIN but not prostate cancer (P < 0.05). In most cases, nuclear expression of EZH2 and SOX2 was detected in less than 10% of cells in non-neoplastic prostate glands, HGPINs or prostate adenocarcinomas. Moreover, 27 of 33 SOX2 1+ prostate cancers were also EZH2 1+, whereas all 33 of these cases were CD44+.


CONCLUSIONS
Expression of CD44 and Oct4 identified large populations of benign and malignant cells in the prostate, which did not fit the definition of stem cells as a small fraction of the total cell population. Our results suggest that combined expression of embryonic stem cell markers EZH2 and SOX2 might identify potential cancer stem cells as a minor (<10%) subgroup in CD44+ prostatic adenocarcinoma.
Ugolkov
Andrey V
AV
Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Eisengart
Laurie J
LJ
Luan
Chunyan
C
Yang
Ximing J
XJ
D000071916:AC133 Antigen; D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D015703:Antigens, CD / Q000032:analysis / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism; D000071221:Enhancer of Zeste Homolog 2 Protein; D006023:Glycoproteins / Q000032:analysis / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis / Q000378:metabolism; D008297:Male; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D050814:Octamer Transcription Factor-3 / Q000032:analysis / Q000378:metabolism; D010455:Peptides / Q000032:analysis / Q000378:metabolism; D063151:Polycomb Repressive Complex 2; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D019048:Prostatic Intraepithelial Neoplasia / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D055748:SOXB1 Transcription Factors / Q000032:analysis / Q000378:metabolism; D014157:Transcription Factors / Q000032:analysis / Q000378:metabolism
D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C000606023:PROM1 protein, human; D010455:Peptides; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2