A subset of high Gleason grade prostate carcinomas contain a large burden of prostate cancer syndecan-1 positive stromal cells.

BACKGROUND: There is a pressing need to identify prognostic and predictive biomarkers for prostate cancer to aid treatment decisions in both early and advanced disease settings. Syndecan-1, a heparan sulfate proteoglycan, has been previously identified as a potential prognostic biomarker by multiple studies at the tissue and serum level. However, other studies have questioned its utility. METHODS: Anti-Syndecan-1 immunohistochemistry was carried out on 157 prostate tissue samples (including cancerous, adjacent normal tissue, and non-diseased prostate) from three independent cohorts of patients. A population of Syndecan-1 positive stromal cells was identified and the number and morphological parameters of these cells quantified. The identity of the Syndecan-1-positive stromal cells was assessed by multiplex immunofluorescence using a range of common cell lineage markers. Finally, the burden of Syndecan-1 positive stromal cells was tested for association with clinical parameters. RESULTS: We identified a previously unreported cell type which is marked by Syndecan-1 expression and is found in the stroma of prostate tumors and adjacent normal tissue but not in non-diseased prostate. We call these cells Prostate Cancer Syndecan-1 Positive (PCSP) cells. Immunofluorescence analysis revealed that the PCSP cell population did not co-stain with markers of common prostate epithelial, stromal, or immune cell populations. However, morphological analysis revealed that PCSP cells are often elongated and displayed prominent lamellipodia, suggesting they are an unidentified migratory cell population. Analysis of clinical parameters showed that PCSP cells were found with a frequency of 20-35% of all tumors evaluated, but were not present in non-diseased normal tissue. Interestingly, a subset of primary Gleason 5 prostate tumors had a high burden of PCSP cells. CONCLUSIONS: The current study identifies PCSP cells as a novel, potentially migratory cell type, which is marked by Syndecan-1 expression and is found in the stroma of prostate carcinomas, adjacent normal tissue, but not in non-diseased prostate. A subset of poor prognosis high Gleason grade 5 tumors had a particularly high PCSP cell burden, suggesting an association between this unidentified cell type and tumor aggressiveness.

Searching for prostate cancer stem cells: markers and methods.

The cancer stem cell hypothesis postulates that a single stem-like cancer cell is able to produce all cancer cell types found in a tumor. These cells are also thought to be the causative agents of relapse following therapy. In order to confirm the importance of cancer stem cells in tumor formation and patient prognosis, their role in prostate cancer must be comprehensively studied. This review describes current methods and markers for isolating and characterizing prostate cancer stem cells, including assays for self-renewal, multipotency and resistance to therapy. In particular the advantages and limitations of these approaches are analyzed. The review will also examine novel methods for studying the lineage of cancer stem cells in vivo using transgenic mouse models. These lineage tracing approaches have significant advantages and, if a number of challenges can be addressed, offer great potential for understanding the significance of cancer stem cells in human prostate cancer.

How important is peritoneal involvement in rectal cancer? A prospective study of 331 cases.

BACKGROUND AND AIMS: The importance of circumferential resection margin involvement in predicting locoregional recurrence and death from rectal cancer is well known. However, it is well accepted that cases of rectal carcinoma recur when this surgical margin is not compromised. The aim of this study was to analyse the influence of peritoneal involvement, among other clinicopathological variables, on locoregional recurrence and overall prognosis in an unselected prospective series of rectal cancer resections. METHODS AND RESULTS: This unselected prospective study assessed 331 rectal carcinoma cases from a colorectal cancer study that recruited more than 1000 cases. Meticulous pathological examination was performed by one pathologist, with particular attention paid to the peritoneal surface. All clinicopathological variables were entered into a database with comprehensive clinical follow-up. Peritoneal involvement was a significant factor in prognosis on univariate analysis but not on multivariate analysis. However, in analysing the causes of locoregional recurrence specifically, it may have been a factor in causing this in up to half the cases. CONCLUSIONS: This study adds to the small amount of literature data on the potential importance of peritoneal involvement in predicting locoregional recurrence and overall prognosis, especially in upper rectal cancer.