Intratumoral inflammation is associated with more aggressive prostate cancer

Purpose

Inflammation may play a role in the development and progression of many cancers, including prostate cancer. We sought to test whether histological inflammation within prostate cancer was associated with more aggressive disease.

Methods

The slides of prostatectomy specimens were reviewed by a board-certified pathologist on 287 men from a Veterans Affairs Medical Center treated with radical prostatectomy from 1992 to 2004. The area with the greatest tumor burden was scored in a blinded manner for the degree of inflammation: absent, mild, or marked. We used logistic and Cox proportional hazards regression analysis to examine whether categorically coded inflammation score was associated with adverse pathology and biochemical progression, respectively.

Results

No inflammation was found in 49 men (17 %), while 153 (53 %) and 85 (30 %) had mild and marked inflammation. During a median follow-up of 77 months, biochemical recurrence occurred among 126 (44 %) men. On multivariate analysis, more inflammation was associated with greater risk of positive margins, capsular penetration, and seminal vesicle invasion (all p < 0.05). Marked inflammation was associated with increased PSA recurrence risk when adjusting for preoperative features only (HR 2.08, 95 % CI 1.02–4.24), but not after adjusting for pathologic features.

Conclusions

Inflammation within prostate cancer was associated with more advanced disease, although it is unclear whether aggressive disease caused increased inflammation or inflammation caused aggressive disease.     

Caveolin-1 overexpression is associated with aggressive prostate cancer recurrence

BACKGROUND: Caveolin-1 protein suppresses apoptotic cell death in prostate cancer. The objectives of this study were to investigate the association of Caveolin-1 expression with established features of prostate cancer as well as overall and aggressive disease recurrence in patients treated with radical prostatectomy (RP). METHODS: Caveolin-1 immunostaining was performed on a tissue microarray containing prostatectomy specimen cores from 232 consecutive patients treated with RP for clinically localized prostatic adenocarcinoma. Caveolin-1 over-expression was defined as more than 50% of cells staining positively for Caveolin-1. Patients were categorized as having features of aggressive disease recurrence if they had a positive metastatic work-up, post-recurrence PSA doubling time less than 10 months, and/or failure to respond to local salvage radiation therapy. RESULTS: Seventy patients (30.2%) exhibited over-expression of Caveolin-1. Caveolin-1 over-expression was associated with higher pathologic Gleason sum (P=0.038) and higher pre-operative PSA level (P=0.024). Patients with Caveolin-1 over-expression were at increased risk of PSA recurrence after surgery (P=0.023) in univariate but not in standard post-operative multivariate analysis. However, patients with Caveolin-1 over-expression were at increased risk of aggressive prostate cancer recurrence in both univariate and multivariate analysis (P<0.001 and P=0.001, respectively). CONCLUSIONS: Over-expression of Caveolin-1 was associated with established features of prostate cancer and aggressive PSA recurrence. Caveolin-1 might help identify patients at high risk of developing aggressive prostate cancer recurrence, thus allowing selection of patients who might benefit from early systemic therapeutic intervention.     

Matrix metalloproteinase-2 polymorphism is associated with prognosis in prostate cancer

ObjectiveProstate cancer (PCa) is the most frequent tumor in males in Brazil. Single nucleotide polymorphisms (SNP) have been demonstrated in the promoter region of matrix metalloproteinases (MMPs) genes and have been associated with development and progression of some cancers. In this study, our aim was to investigate a possible relation between polymorphism of the promoter region of the MMP2 gene and classical prognostic parameters in prostate cancer.Materials and methodsGenomic DNA was extracted using conventional protocols. The DNA sequence containing the polymorphic site was amplified by real-time polymerase chain reaction, using fluorescent probes (TaqMan).ResultsIn patients with tumors of a higher stage (pT3), a polymorphic allele in the MMP2 gene was more frequent (P = 0.026) than in patients with lower tumor stage. A polymorphic allele in the MMP2 gene was more frequent in Gleason ≥ 7 than in Gleason ≤ 6 (P = 0.042).ConclusionsWe conclude that MMP2 polymorphism can be used together with pathological stage and Gleason score to identify patients with worse prognosis. Our results illustrate the potential use of MMP2 SNP as a molecular marker for prostate cancer.     

Human kallikrein-2 gene polymorphism is associated with the occurrence of prostate cancer

PURPOSE: Human glandular kallikrein, which is encoded by the human kallikrein-2 (KLK2) gene, is significantly associated with the occurrence of prostate cancer (PCa). We tested the association between a functional C748T polymorphism of the KLK2 gene and the occurrence of PCa. MATERIALS AND METHODS: Peripheral venous blood samples were obtained from 254 patients with PCa and 168 controls with benign prostatic hyperplasia. All control subjects had normal serum prostate specific antigen and proved to be free from malignancy on pathological examination of resected prostatic tissues. Serum prostate specific antigen, testosterone, Gleason score, clinical and pathological stage, tumor and prostate volume of the patients were investigated. The KLK2 gene polymorphism was determined by the polymerase chain reaction based restriction fragment length polymorphism method. RESULTS: The PCa group had a younger mean age +/- SEM (73.0 +/- 0.5 vs 74.7 +/- 0.5 years, p = 0.010) and higher C allele frequency (82.1% vs 74.7%, p = 0.010) than the control group. The frequency of the CC, CT and TT genotypes was 65.7%, 32.7% and 1.6% in patients with PCa, and 56.0%, 37.5% and 6.5%, respectively, in controls (p = 0.010). C allele carriers (CC and CT genotypes) were at significantly higher risk for PCa than TT homozygous subjects (p = 0.002). CC homozygous subjects were at significantly higher risk for PCa than T allele carriers (CT and TT genotypes) (p = 0.043). The PCa subgroup of patients with pathologically proved, localized PCa also had a higher frequency of the C allele (87.5% vs 74.7%, p = 0.026) and CC genotypes (78.7% vs 56.0%, p = 0.019) than controls. CONCLUSIONS: Our results suggest that the C allele of the functional C748T polymorphism of KLK2 may increase the risk of PCa.     

Is prostate cancer more common and more aggressive in African men?

The highest prostate cancer incidence and mortality rates in the world have been reported among Black African-American men (AAM) living in the United States of America. These rates are significantly higher for AAM compared to White (Caucasian) American men (CAM). However, prostate cancer is not the only malignancy which is more common in AAM compared to White American men or women. Although prostate cancer has the highest Black/White mortality ratio, it is not the only malignancy which has a higher mortality in AAM compared to CAM.     

E-cadherin gene 3'-UTR C/T polymorphism is associated with prostate cancer

INTRODUCTION: E-cadherin (CDH-1) is a cell-cell adhesive molecule which maintains cell integrity and communication between the intracellular and extracellular world. CDH-1 may therefore be related to carcinogenesis. A polymorphism located at the 3'-UTR of the CDH-1 gene is associated with stone disease; however, its relationship to prostate cancer has not been reported. We aimed to study whether there is an association between the 3'-UTR polymorphism and prostate cancer. MATERIALS AND METHODS: We collected 96 patients with prostate cancer and 114 normal controls for this study. The polymorphism of the CDH-1 gene was studied by polymerase chain reaction-based restriction analysis. RESULTS: There was a significant difference in genotype distribution of the CDH-1 gene polymorphism between cancer patients and normal controls (p < 0.001). The distribution of the CDH-1 gene CC genotype in prostate cancer patients (51.0%) was higher than in the controls (10.5%). The odds ratio for the CDH-1 'C' allele was 2.896 (95% CI = 1.908-4.396). There was no significant difference according to age, pathological grading, clinical staging, and responsiveness to hormonal therapy among patients. Only 3 patients (3.1%) had a history of urolithiasis. CONCLUSIONS: The CDH-1 gene 3'-UTR C/T polymorphism is associated with prostate cancer. The 'CC' homozygote indicates a relatively higher risk for developing prostate cancer than other genotypes.     

Self-reported acne is not associated with prostate cancer

ObjectiveSome studies have suggested an inverse association between acne vulgaris and the acne-related bacterium Propionibacterium acnes and prostate cancer (PCa). Self-reported acne might be an easily obtainable marker to identify men at relatively low risk of PCa and might be incorporated into PCa risk calculators. This study aimed to evaluate the association between self-reported acne and PCa in a large case-referent study.Methods and materialsThe case group comprised 942 patients with PCa recruited from a population-based cancer registry in 2003 to 2006, 647 of whom met the criteria for aggressive PCa. The referents (n = 2,062) were a random sample of the male general population. All subjects completed a questionnaire on risk factors for cancer, including questions about acne. Odds ratios (ORs) and 95% confidence interval (CI) were calculated using multivariable logistic regression for PCa and aggressive PCa as separate end points, while adjusting for age and family history of PCa.ResultsA history of acne was reported by 320 cases (33.9%) and 739 referents (35.8%). Self-reported acne was significantly associated neither with PCa (adjusted OR = 0.95, 95% CI: 0.80–1.12) nor with aggressive PCa (adjusted OR = 0.97, 95% CI: 0.80–1.18).ConclusionSelf-reported acne is not suitable as a marker to identify men at low risk of aggressive PCa.     

Interleukin-2 gene polymorphism is associated with renal but not cardiac transplant outcome

It was recently shown that IL-2 gene single nucleotide polymorphism (SNP) at position -330 (G-->T) is related to in vitro cytokine production levels, with the T/T and T/G genotypes being associated with low production and the G/G genotype associated with high production. The objective of this study was to investigate a possible influence of this polymorphism on renal and cardiac allograft outcomes. IL-2 SNP G-T (-330) was determined by PCR-RFLP in 67 recipients of heart allografts and in 63 recipients of renal grafts from HLA-haplo-identical, related donors. A higher frequency of the T/T genotype was observed in renal transplant patients who experienced at least one acute rejection episode during the first 3 months after transplantation than in those without rejection during this period (80% vs 49%, respectively, P <.05). Accordingly, the same genotype tended to be more frequent in renal recipients with a 6-month serum creatinine level above 1.5 mg/dL (median value for the whole group of kidney recipients) than in patients with lower creatinine levels (79% vs 45%, P <.08). Regarding cardiac transplant recipients, no associations were observed concerning acute rejection or graft survival. The finding of the association of T/T but not T/G genotype with acute kidney rejection was unexpected considering that both genotypes were shown to be associated with equal (low) IL-2 in vitro production. Further studies are necessary not only to dissect the nature of IL-2 T/T genotype association with kidney rejection, but also to explain why this genotype does not apparently influence cardiac allograft outcome.     

p53 gene codon 72 polymorphism but not tumor necrosis factor-alpha gene is associated with prostate cancer

OBJECTIVE: A polymorphism of gene p53 codon 72 is associated with various cancer formations. Tumor necrosis factor-alpha (TNF-alpha) one of the cytokines secreted by macrophages in response to inflammation and is also related to cancer formation. We aimed to evaluate the association between prostate cancer and the polymorphisms of the TNF-alpha gene promoter -308 and p53 gene codon 72. PATIENTS AND METHODS: In our study, a normal control group of 126 healthy people and 96 patients with prostate cancer were examined. The polymorphism (G/A) of TNF-alpha gene was detected by polymerase chain reaction (PCR)-based restriction analysis (Nco I endonuclease) and the polymorphism of p53 gene was detected by two PCRs (one for proline and one for arginine form). RESULTS: There was a significant difference in the distribution of codon 72 polymorphism the p53 gene between prostate cancer patients and the normal controls (p < 0.001). The proline form of p53 gene codon 72 was significantly higher than the arginine form, with an odds ratio of 2.606 (95% CI = 1.052-6.455). This difference was also revealed in the tumor staging (p = 0.035) as the proline form was significantly higher in the metastasis group of prostate cancer. There were no statistical differences in the distribution of -308 polymorphism of the TNF-alpha gene between cancer patients and the control subjects (p = 1.0). CONCLUSION: Prostate cancer appears to be associated with the p53 gene codon 72 polymorphisms, but not with the TNF-alpha gene. The proline form of p53 gene codon 72 might be a more significant risk factor for the development of metastasis than the arginine form.