Faculty Bibliography

PURPOSE: The Cooperative Prostate Cancer Tissue Resource (CPCTR) is a National Cancer Institute-supported tissue bank that provides large numbers of clinically annotated prostate cancer specimens to investigators. This communication describes the CPCTR to investigators interested in obtaining prostate cancer tissue samples. EXPERIMENTAL DESIGN: The CPCTR, through its four participating institutions, has collected specimens and clinical data for prostate cancer cases diagnosed from 1989 onward. These specimens include paraffin blocks and frozen tissue from radical prostatectomy specimens and paraffin blocks from prostate needle biopsies. Standardized histopathological characterization and clinical data extraction are performed for all cases. Information on histopathology, demography (including ethnicity), laboratory data (prostate-specific antigen values), and clinical outcome related to prostate cancer are entered into the CPCTR database for all cases. Materials in the CPCTR are available in multiple tissue formats, including tissue microarray sections, paraffin-embedded tissue sections, serum, and frozen tissue specimens. These are available for research purposes following an application process that is described on the CPCTR web site (www.prostatetissues.org). RESULTS: The CPCTR currently (as of October 2003) contains 5135 prostate cancer cases including 4723 radical prostatectomy cases. Frozen tissues, in some instances including patient serum samples, are available for 1226 cases. Biochemical recurrence data allow identification of cases with residual disease, cases with recurrence, and recurrence-free cases. CONCLUSIONS: The CPCTR offers large numbers of highly characterized prostate cancer tissue specimens, including tissue microarrays, with associated clinical data for biomarker studies. Interested investigators are encouraged to apply for use of this material (www.prostatetissues.org)

BACKGROUND: Tissue Microarrays (TMAs) have emerged as a powerful tool for examining the distribution of marker molecules in hundreds of different tissues displayed on a single slide. TMAs have been used successfully to validate candidate molecules discovered in gene array experiments. Like gene expression studies, TMA experiments are data intensive, requiring substantial information to interpret, replicate or validate. Recently, an open access Tissue Microarray Data Exchange Specification has been released that allows TMA data to be organized in a self-describing XML document annotated with well-defined common data elements. While this specification provides sufficient information for the reproduction of the experiment by outside research groups, its initial description did not contain instructions or examples of actual implementations, and no implementation studies have been published. The purpose of this paper is to demonstrate how the TMA Data Exchange Specification is implemented in a prostate cancer TMA. RESULTS: The Cooperative Prostate Cancer Tissue Resource (CPCTR) is funded by the National Cancer Institute to provide researchers with samples of prostate cancer annotated with demographic and clinical data. The CPCTR now offers prostate cancer TMAs and has implemented a TMA database conforming to the new open access Tissue Microarray Data Exchange Specification. The bulk of the TMA database consists of clinical and demographic data elements for 299 patient samples. These data elements were extracted from an Excel database using a transformative Perl script. The Perl script and the TMA database are open access documents distributed with this manuscript. CONCLUSIONS: TMA databases conforming to the Tissue Microarray Data Exchange Specification can be merged with other TMA files, expanded through the addition of data elements, or linked to data contained in external biological databases. This article describes an open access implementation of the TMA Data Exchange Specification and provides detailed guidance to researchers who wish to use the Specification

PURPOSE: The protein encoded by N-myc downstream-regulated gene 1 (NDRG1) is a recently discovered protein whose transcription is induced by androgens and hypoxia. We hypothesized that NDRG1 expression patterns might reveal a biological basis for the disparity of clinical outcome of prostate cancer patients with different ethnic backgrounds. EXPERIMENTAL DESIGN: Patients who underwent radical prostatectomy between 1990 and 2000 at Veterans Administration Medical Center of New York were examined. We studied 223 cases, including 157 African Americans and 66 Caucasians (T2, n = 144; >/=T3, n = 79; Gleason <7, n = 122; >/=7, n = 101). Three patterns of NDRG1 expression were identified in prostate cancer: (a) intense, predominately membranous staining similar to benign prostatic epithelium; (b) intense, nucleocytoplasmic localization; and (c) low or undetectable expression. We then examined the correlations between patients' clinicopathological parameters and different NDRG1 expression patterns. RESULTS: In this study of patients with equal access to care, African-American ethnic origin was an independent predictor of prostate-specific antigen recurrence (P < 0.05). We also observed a significant correlation between different patterns of NDRG1 expression and ethnic origin. Pattern 2 was less frequent in African Americans (21% versus 38%), whereas the reverse was observed for pattern 3 (60% in African Americans versus 44% in Caucasians; P = 0.03). This association remained significant after controlling for both grade and stage simultaneously (P = 0.02). CONCLUSIONS: Our data suggest that different NDRG1 expression patterns reflect differences in the response of prostatic epithelium to hypoxia and androgens in African-American compared with Caucasian patients. Further studies are needed to determine the contribution of NDRG1 to the disparity in clinical outcome observed between the two groups

PURPOSE: We developed an algorithm that prospectively defines when to excise the neurovascular bundles during radical retropubic prostatectomy with the goal of maximizing the performance of nerve sparing procedures while minimizing positive surgical margins. MATERIALS AND METHODS: From January 1 to December 31, 2000 a single surgeon performed 272 radical retropubic prostatectomies and 263 were performed from January 1 to December 31, 2001. A single pathologist analyzed all specimens with positive margins. There were no prospectively defined criteria to guide decisions regarding excision of the neurovascular bundles in the 2000 study cohort. Gleason score, percent tumor volume and perineural invasion were independently analyzed in the biopsy specimens according to the site of origin (right versus left side) for the 2001 group only. The ipsilateral neurovascular bundle was excised for Gleason 6 or less tumors when there were 50% or greater tumor volume in the biopsy specimen and perineural invasion, for Gleason 7 tumors when there was 30% or greater tumor volume, or perineural invasion and for Gleason 8 to 10 tumors when there was 10% or greater tumor volume, or perineural invasion. RESULTS: There were no statistically significant differences between the 2000 and 2001 groups in regard to preoperative prostate specific antigen, clinical and pathological stage, biopsy Gleason score and percent tumor volume in the surgical specimen. There was a statistically significant decrease in the incidence of positive margins between the 2000 and 2001 groups (14% versus 8%, p = 0.027). The lower positive margin rate was not achieved because of a tendency to excise more neurovascular bundles since a significantly greater percent of neurovascular bundles was preserved in the 2001 group. The sensitivity, specificity, positive and negative predictive values, and accuracy of our algorithm were 18%, 93%, 28%, 89% and 84%, respectively. In sides of the prostate with extraprostatic extension ipsilateral wide excision of the neurovascular bundle was associated with positive margins in 33% of cases compared with 22% when the neurovascular bundle was preserved (p = 0.42). CONCLUSIONS: The New York University nerve sparing algorithm prospectively defines when to excise the neurovascular bundle based on Gleason score, perineural invasion and tumor volume in the biopsy specimen. Use of this algorithm decreases positive surgical margin rates, while significantly increasing the preservation of neurovascular bundles