Early growth response 1 and fatty acid synthase expression is altered in tumor adjacent prostate tissue and indicates field cancerization.

BACKGROUND: Field cancerization denotes the occurrence of molecular alterations in histologically normal tissues adjacent to tumors. In prostate cancer, identification of field cancerization has several potential clinical applications. However, prostate field cancerization remains ill defined. Our previous work has shown up-regulated mRNA of the transcription factor early growth response 1 (EGR-1) and the lipogenic enzyme fatty acid synthase (FAS) in tissues adjacent to prostate cancer. METHODS: Immunofluorescence data were analyzed quantitatively by spectral imaging and linear unmixing to determine the protein expression levels of EGR-1 and FAS in human cancerous, histologically normal adjacent, and disease-free prostate tissues. RESULTS: EGR-1 expression was elevated in both structurally intact tumor adjacent (1.6× on average) and in tumor (3.0× on average) tissues compared to disease-free tissues. In addition, the ratio of cytoplasmic versus nuclear EGR-1 expression was elevated in both tumor adjacent and tumor tissues. Similarly, FAS expression was elevated in both tumor adjacent (2.7× on average) and in tumor (2.5× on average) compared to disease-free tissues. CONCLUSIONS: EGR-1 and FAS expression is similarly deregulated in tumor and structurally intact adjacent prostate tissues and defines field cancerization. In cases with high suspicion of prostate cancer but negative biopsy, identification of field cancerization could help clinicians target areas for repeat biopsy. Field cancerization at surgical margins on prostatectomy specimen should also be looked at as a predictor of cancer recurrence. EGR-1 and FAS could also serve as molecular targets for chemoprevention.

SEER coding standards result in underestimation of positive surgical margin incidence at radical prostatectomy: results of a systematic audit.

PURPOSE: SEER (Surveillance, Epidemiology and End Results) is the leading source of population level data on prostate cancer, including the positive surgical margin incidence at radical prostatectomy. Recently studies showed wide ranges in positive surgical margin rates among individual registries, which we hypothesized was the result of coding inaccuracies. Thus, we systematically audited SEER prostate cancer data. MATERIALS AND METHODS: The New Mexico Tumor Registry, a SEER core registry, was queried for incident prostate cancer cases in 2007 that met certain criteria, including 1) adenocarcinoma histology, 2) malignant behavior and 3) radical prostatectomy as the first course of therapy. Pathological stage codes were audited by examining original radical prostatectomy pathology reports in accordance with SEER coding guidelines. The incidence and sites of positive surgical margins were critically analyzed. RESULTS: Of the 305 cases that met all study inclusion criteria with complete source documents available 92 (30%) were coded incorrectly. The most common error was failure to properly account for surgical margin status (46 of 92 cases or 50%). The incidence of positive surgical margins in organ confined disease cases was 13% by SEER coding rules but 28% by a more clinical definition of positive surgical margins (p<0.001). In organ confined cases positive surgical margins occurred principally at the apex but in nonorgan confined cases most were multifocal. CONCLUSIONS: In this SEER registry 30% of radical prostatectomy cases in 2007 were coded inaccurately. SEER coding guidelines result in underestimating the positive surgical margin incidence. Clinicians and investigators should recognize the limitations of tumor registry data on positive surgical margins.

Organ-wide telomeric status in diseased and disease-free prostatic tissues.

BACKGROUND: Telomere attrition occurs early in the development of prostatic adenocarcinoma. However, little is known about either telomere status in benign prostatic hyperplasia (BPH), or the spatial and organ-wide distribution of potential telomere aberrations throughout all areas of prostatic glands affected by cancer or BPH. METHODS: Slot blot titration assay was used to determine telomere DNA content (TC), a proxy for telomere length, in macrodissected tissue consisting of 54 normal samples from 5 disease-free prostates, 128 BPH samples from 4 non-cancerous prostates, and 45 tumor, 73 BPH, and 4 prostatic intraepithelial neoplasia (PIN) samples from 5 cancerous prostates. RESULTS: Compared to TC in normal prostate samples (n = 54; TC mean = 0.98), tumor samples displayed telomere attrition (n = 45; TC mean = 0.67). TC in PIN samples was similar to tumors. TC in BPH samples from cancerous prostates was similar to TC in tumors and also displayed telomere shortening (n = 73; TC mean = 0.76), whereas BPH samples from non-cancerous prostates displayed longer telomeres (n = 128; TC mean = 1.06). In prostates affected by adenocarcinoma, areas of potential telomere attrition occurred in histologically normal tissues through the entire gland. However, three-dimensional zoning revealed a pattern of increasing TC as a function of distance from the primary (index) tumor. CONCLUSIONS: Spatial distributions of TC in prostate specimens indicate a complex "field effect" with varying contributions from both cancer and BPH. The observation that telomere length variations occur in fields of histologically normal tissues surrounding the tumor is of clinical importance, as it may have implications for the diagnosis and focal therapy of prostate cancer.