HE PREVALENCE OF OBESITY IN the United States has dramatically increased in the past decade. 1 Increased body mass index (BMI) has been linked to death from colon, breast, and many other cancers. 2 Although there are biological bases for increased risk of certain cancers in obese persons, 3 delayed diagnosis may provide an explanation for advanced stage of disease and poor outcome. Obesity presents technical problems for cancer detection, since adiposity may hinder physical examination and interfere with imaging and ancillary tests. 4 Likewise, obesity may negatively affect early diagnosis through assessment of serum concentrations of soluble tumor markers. For example, recent evidence suggests that prostate cancer screening may be adversely affected by increased BMI. 5 In the United States, most prostate cancer cases are diagnosed by needle biopsy of the prostate prompted by a high serum prostate-specific antigen (PSA) concentration. The ability to accurately detect prostate cancer can be compromised by any factor that decreases PSA concentration in the circulation. Multiple studies have found that obese men have lower PSA con-Author Affiliations are listed at the end of this article.

Background: Protein expression profiling for differences indicative of early cancer has promise for improving diagnostics. This report describes the first stage of a National Cancer Institute/Early Detection Research Network-sponsored multiinstitutional evaluation and validation of this approach for detection of prostate cancer. Methods: Two sequential experimental phases were conducted to establish interlaboratory calibration and standardization of the surface-enhanced laser desorption (SELDI) instrumental and assay platform output.

BACKGROUND: This report and a companion report describe a validation of the ability of serum proteomic profiling via SELDI-TOF mass spectrometry to detect prostatic cancer. Details of this 3-stage process have been described. This report describes the development of the algorithm and results of the blinded test for stage 1.

Obesity is associated with increased risk of positive surgical margins and prostate specific antigen (PSA) recurrence among men undergoing radical prostatectomy. To what degree positive margins contribute to poorer outcome is unclear. Thus, we sought to examine the association between body mass index (BMI) and more objective measures of tumor aggressiveness, tumor grade and size. We carried out a retrospective analysis of 2302 patients treated with radical prostatectomy at the Duke Prostate Center from 1988-2007. Tumor volume was calculated by multiplying prostate weight by percent of specimen involved with cancer. Associations between BMI and tumor volume and highgrade disease (GleasonX4 þ 3) independent of pre-operative clinical characteristics of age, race, PSA, clinical stage, biopsy Gleason sum, and year of surgery were assessed using linear and logistic regression, respectively. Mean and median BMI among all subjects was 28.1 and 27.6 kg m -2 , respectively. Increased BMI was significantly associated with younger age (Po0.001), black race (Po0.001), more recent year of surgery (Po0.001), and positive surgical margins (Po0.001). After adjusting for multiple clinical pre-operative characteristics, higher BMI was associated with a greater percent of the prostate involved with cancer (P ¼ 0.003), increased tumor volume (Po0.001), and high-grade disease (P ¼ 0.007). Men with a BMI X35 kg m 2 had nearly 40% larger mean tumor volumes than normal weight men (5.1 versus 3.7 cc), after adjustment for multiple clinical characteristics. In this study, obese men undergoing radical prostatectomy had higher-grade and larger tumors, providing further evidence that obese men undergoing radical prostatectomy have more aggressive prostate cancers.

PITX2 methylation status assessed by EpiChip PITX2 identifies patients with prostate cancer who are most likely to have biochemical recurrence. This test independently adds to the prognostic information provided by standard clinicopathological analysis, improving prostatectomy case stratification into those at high and low risk for biochemical recurrence. This new clinical tool would be of particular benefit to assess intermediate risk cases (Gleason 7) in which risk stratification remains a challenge.

These preliminary findings support recent observations that complex protein profiles have promising potential for the early detection of CaP and warrant future studies with streamlined technology. Furthermore, the combined effect of using 2 array types can greatly enhance the ability of protein profile patterns, suggesting the potential usefulness of alternative approaches to evaluate this new emerging technology.

A wide array of biomarkers is being investigated as predictors of prostate cancer (PCa) diagnosis and recurrence. We compared the expression of a small panel of these biomarkers as a function of race among men undergoing radical prostatectomy (RP). Prostate needle biopsy specimens from 131 patients treated with RP at the Durham Veterans Affairs Medical Center were hematoxylin and eosin stained and immunofluorescent assayed for α-methylacyl CoA racemase (AMACR), androgen receptor (AR) and Ki67. Proprietary image analysis was used to identify six biometric feature combinations that were significantly associated with progression in a previous study. Analysis of population characteristics, stratified by race, was performed using rank-sum and χ(2)-test. The effect of race on expression of these biomarker profiles was analyzed using multivariate linear regression. All six biomarker features were expressed at higher levels in black men than white men, with Norm AR (P=0.006) and Ki67 (P=0.02) attaining statistical significance. On multivariate analysis, all markers were expressed at higher levels in black men, with Norm AR (P=0.001), Ki67 (P=0.007) and Ki67/lum (P=0.022) reaching significance. These data support the hypothesis that PCa may be biologically more aggressive among black men.

Black race was associated with discontinuation of AS for treatment. This relationship persisted when adjusted for socioeconomic and clinical parameters.