Background: Cancer stem cells are defined by their self-renewal and multi-potential capabilities and are hypothesized to be the source of primary and recurrent cancers. The stem cell properties of self-renewal and pluripotency in embryonic stem cells and germ cells are regulated by Oct4A, a splice variant of the POU5F1 (Oct3/4) gene, while the function of the alternative splice variant, Oct4B, is unknown. Rare cells that express Oct4 were identified in several somatic cancers, however, the differential contributions of the Oct4A and Oct4B variants were not determined.
Methods: Oct4A expression and co-localization with lineage markers was performed with PCR and immunohistochemistry.
Results: Rare Oct4A expressing cells are present in human benign and malignant prostate glands and the number of Oct4A expressing cells increases in prostate cancers with high Gleason scores. Oct4A expressing cells were non-proliferative, and did not co-express markers of basal epithelial cell or luminal epithelial cell differentiation, or AMACR, a marker of prostate cancer epithelial cells. A subpopulation of the Oct4A expressing cells co-expressed Sox2, an embryonic stem cell marker, but did not express other putative stem cell markers, such as ABCG2, NANOG or CD133. The majority of Oct4A expressing cells co-expressed chromogranin A, and a subset of Oct4A expressing cells co-expressed synaptophysin, both markers of neuroendocrine differentiation.
Conclusion: The increased number of cells that expressed Oct4A in prostate cancer compared to benign prostate, and in cancers of increasing grade, suggests that Oct4A/Chromogranin A co-expressing cells represent neuroendocrine cells in prostate cancer.
2008 Wiley-Liss, Inc.