Expression of bFGF/FGFR-1 and vascular proliferation related to clinicopathologic features and tumor progress in localized prostate cancer

Microvessel density (MVD) has been associated with progression of prostate cancer. Although basic fibroblast growth factor (bFGF) is a known endothelial mitogen, the prognostic role of bFGF and its receptor FGFR-1 in prostate cancer has been controversial. The aim of our study was to examine the tissue distribution and prognostic significance of bFGF, FGFR-1, and microvascular proliferation. Sections from 104 radical prostatectomy specimens were examined by factor VIII/Ki-67 staining for proliferating capillary index (PCI) and MVD, and tissue microarray sections were immunostained for bFGF and FGFR-1. Increased PCI (median 0.49%) was related to strong stromal expression of bFGF (P=0.003) but was without prognostic impact. Strong bFGF staining was associated with well-differentiated tumors, no capsular penetration, low serum-prostate-specific antigen (s-PSA), low tumor cell proliferation, and increased time to biochemical failure (P=0.007), and was of independent prognostic importance in multivariate survival analysis. bFGF expression in vessels was associated with low MVD (P=0.0003). In contrast, strong tumor cell FGFR-1 expression was related to high preoperative s-PSA. Thus, increased stromal and vessel bFGF was associated with less aggressive tumors. Our findings indicate a complex relationship between bFGF/FGFR-1 expression and prognosis of prostate cancer. Vascular proliferation revealed no prognostic impact in this study.     

Matrix metalloproteinase 9 is associated with Gleason score in prostate cancer but not with prognosis

Prostate cancer is the most common cancer in North American men. Among men diagnosed with prostate cancer in more than three cores or with high grade prostate cancer, many experience long disease-free survival. However, these patients still undergo radical treatment while they could benefit from active surveillance with complementary therapy. Matrix metalloproteinase 9 degrades type IV collagen and activates tumorigenic factors and is thus a potential prognostic factor and therapeutic target. This study was thus aimed at investigating the role of matrix metalloproteinase 9 on prostate cancer progression. We correlated matrix metalloproteinase 9 immunohistochemical expression by cancer, stromal and benign epithelial cells with prostate cancer disease-free survival among a cohort composed of 187 pT3NxM0 prostate cancer patients. Median follow-up was 4.63 years and a recurrence occurred in 67 men (35.3%). Matrix metalloproteinase 9 immunostaining was cytoplasmic and expressed at different levels in cancer (94.1%), stromal (87.7%) and benign epithelial cells (94.1%). High levels (>50% of cells) of matrix metalloproteinase 9 expression by prostate cancer cells was strongly associated with high Gleason score (P = .0009). In stromal cells and in benign epithelial cells, high matrix metalloproteinase 9 expression levels were respectively associated with low pT3 substage (P = .046) and with low initial serum prostate-specific antigen levels (P = .006). Matrix metalloproteinase 9 expression level by any cell type was not associated with prostate cancer disease-free survival. These results show that matrix metalloproteinase 9 is overexpressed by cancer cells in high grade tumors and by stromal and benign epithelial cells in lower substage tumors.     

High-level cytoplasmic cyclin D1 expression in lymph node metastases from prostate cancer independently predicts early biochemical failure and death in surgically treated patients

Fleischmann A, Rocha C, Saxer‐Sekulic N, Zlobec I, Sauter G & Thalmann G N
(2011) Histopathology 58 , 781–789
High‐level cytoplasmic cyclin D1 expression in lymph node metastases from prostate cancer independently predicts early biochemical failure and death in surgically treated patients Aims: To test the prognostic significance of cyclin D1 in nodal‐positive prostate cancer. Methods and results: Nuclear and cytoplasmic cyclin D1 expression was evaluated in 119 nodal‐positive prostate cancer patients undergoing radical prostatectomy and extended lymphadenectomy. Cyclin D1 was correlated with various tumour features and biochemical recurrence‐free survival (bRFS), disease‐specific survival (DSS) and overall survival (OS). In the metastases, high‐level cytoplasmic cyclin D1 expression independently predicted poor outcome (5‐year bRFS, 12.5% versus 26.4%, P = 0.006; 5‐year DSS, 56.3% versus 80.7%, P = 0.007; 5‐year OS, 56.3% versus 78.7%, P = 0.011). These patients had a 2.62‐fold elevated risk of dying from prostate cancer as compared with patients with low‐level cytoplasmic cyclin D1 expression (P = 0.024). All other subcellular compartments of cyclin D1 expression in primary tumours and metastases were prognostically non‐significant. Conclusions: The subcellular location of cyclin D1 expression in prostate cancer is linked to specific clinical courses. Survival stratification according to biomarker expression in metastases indicates an important role for tumour sampling from these tissues.     

Group IIA phospholipase A2 as a prognostic marker in prostate cancer: relevance to clinicopathological variables and disease‐specific mortality

Group IIA Phospholipase A₂ (PLA2‐IIA), a key enzyme in arachidonic acid and eicosanoid metabolism, participates in a variety of inflammatory processes but possibly also plays a role in tumor progression in vivo. Our aim was to determine the mRNA and protein expression of PLA2‐IIA during prostate cancer progression in localized and metastatic prostate tumors. We evaluated the prognostic significance of PLA2‐IIA expression in biochemical recurrence, clinical recurrence and disease‐specific survival after surgical treatment. The expression of PLA2‐IIA was examined by immunohistochemistry and chromogenic in situ hybridization in tissue microarrays of radical prostatectomy specimens and advanced/metastatic carcinomas. The expression data were analyzed in conjunction with clinical follow‐up information and clinicopathological variables. The mRNA and protein expression of PLA2‐IIA was significantly increased in Gleason pattern grade 2–4 carcinomas compared with benign prostate (p‐values 0.042–0.001). In metastases, the expression was significantly lower than in local cancers (p=0.001). The PLA2‐IIA expression correlated positively with Ki‐67 and α‐methylacyl CoA racemase (AMACR) expression. The prognostic evaluation revealed decreased PLA2‐IIA protein expression among patients who had died of prostate cancer. In conclusion, PLA2‐IIA expression is increased in carcinoma when compared with benign prostate. However, metastatic carcinoma showed decreased expression of PLA2‐IIA when compared with primary carcinomas. PLA2‐IIA may serve as a marker for highly proliferating, possibly poorly differentiated prostate carcinomas. The protein expression of PLA2‐IIA may be diminished in patients who consequently die of prostate cancer.     

The expression level of lysophosphatidylcholine acyltransferase 1 (LPCAT1) correlates to the progression of prostate cancer

BackgroundLysophosphatidylcholine acyltransferase 1 (LPCAT1), the enzyme catalyzing the reaction in remodeling of phosphatidylcholine (PC) has been reported to express in prostate. However, its diagnostic and prognostic values remain unclear.MethodsImmunohistochemistry (IHC) for LPCAT1was performed on the tissue microarray (TMA) slides containing 251samples from 148 patients with various prostatic disorders. The association of expression level of LPCAT1 with the progression of prostate cancer was analyzed.ResultsLPCAT1 IHC mean score was the highest in metastatic prostate cancer (8.00 ± 1.28), which was significantly higher than that in primary prostate cancer (4.63 ± 3.00, p = 9.73E-07), in high grade prostatic intraepithelial neoplasia (HGPIN, 2.72 ± 2.47, p = 1.02E-12), and in benign prostate (2.68, p = 6.17E-12). The mean score in primary prostate cancer was significantly higher than that in HGPIN (p = 4.09E-04) and in benign prostate (p = 2.74E-04). There was no significant difference in the mean score between HGPIN and benign prostate (p = 0.951). LPCAT1 IHC score also correlated to the tumor grade and stage of prostate cancer. Patients who underwent prostatectomy for prostate cancer and developed biochemical recurrence or clinical metastasis had higher LPCAT1 IHC score than those who underwent prostatectomy for prostate cancer and did not develop biochemical recurrence and clinical metastasis. The association of LPCAT1 with the progression of prostate cancer was independent of patient race and age, PSA level and positivity of surgical resection margins.ConclusionsLPCAT1 correlates with the progression of prostate cancer and could be a new biomarker in diagnosis, prognosis and studying the pathogenesis of prostate cancer.     

Low activated leukocyte cell adhesion molecule expression is associated with advanced tumor stage and early prostate-specific antigen relapse in prostate cancer

Activated leukocyte cell adhesion molecule (CD166) is a member of the immunoglobulin superfamily and is aberrantly expressed in different tumors, including prostate cancer. To learn more on the prevalence and clinical significance of activated leukocyte cell adhesion molecule expression in prostate cancer, a tissue microarray containing 3261 primary prostate cancers treated by radical prostatectomy was used. A total of 2390 different prostate cancers were analyzed by immunohistochemistry in a tissue microarray format. Activated leukocyte cell adhesion molecule immunostaining in cancers was compared with clinical follow-up, which was available for 1746 patients. Membranous activated leukocyte cell adhesion molecule immunostaining was recorded in 1663 (69.6%) of cases. High activated leukocyte cell adhesion molecule expression levels were significantly associated with favorable tumor features (pT: P = .0015; pN: P = .0008; preoperative prostate-specific antigen: P = .0057) and a lower risk of a biochemical recurrence (P = .0067). Cytoplasmatic activated leukocyte cell adhesion molecule staining was usually associated with membranous staining. The small number of cancers with pure cytoplasmatic staining did not reveal any particularities with respect to clinical outcome or tumor phenotype. It is concluded that activated leukocyte cell adhesion molecule protein is almost always expressed in prostate cancer and that decreased levels of activated leukocyte cell adhesion molecule expression may lead to an aggressive behavior of tumor cells. The abundant presence of activated leukocyte cell adhesion molecule and its membranous localization in prostate cancer epithelium make activated leukocyte cell adhesion molecule a potentially attractive structure for targeted therapy.     

13q deletion is linked to an adverse phenotype and poor prognosis in prostate cancer

Deletions of chromosome arm 13q belong to the most frequent molecular alterations in prostate cancer. To better understand the role of 13q deletion in prostate cancer we took advantage of our large prostate cancer tissue microarray comprising more than 12 000 cancer samples with full pathological and clinical follow‐up data. Fluorescence in situ hybridization with probes for ENOX1 (13q14.11) and the retinoblastoma gene (RB1, 13q14.2) was employed. A 13q deletion was found in 21% of 7375 analyzable cancers. Deletions were always heterozygous and associated with high Gleason grade (P < .0001), advanced tumor stage (P < .0001), high preoperative prostate‐specific antigen (PSA) levels (P = .0125), lymph node metastasis (P = .0377), positive resection margin (P = .0064), and early biochemical recurrence (P < .0001). 13q deletions were marginally more frequent in prostate cancers with negative ERG status (22.9%) than in ERG‐positive tumors (18.7%; P < .0001). Loss of 13q predicted patient prognosis independently from established prognostic parameters that are available at the time of biopsy (P = .0004), including preoperative PSA level, clinical tumor stage, and biopsy Gleason grade. In summary, the results of our study identify 13q deletion as a frequent event in prostate cancer, which is linked to an adverse phenotype and poor prognosis in this disease.     

Expression and significance of cortactin and HDAC6 in human prostatic foamy gland carcinoma

Cortactin, the cytoplasmic substrate of HDAC6, is known to play an actin cytoskeletal regulatory role which is implicated in the motility of cancer cells, and thus in cancer progression. Its activity is found to be regulated by HDAC6. However, the significance of cortactin and HDAC6 remains unclear in uncommon histologic variant human prostatic foamy gland carcinoma (PfCa). In this study, we aimed to identify the expression and potential role of cortactin and HDAC6 in PfCa. Therefore, 16 PfCa specimens containing 48 foci with distinctive lesions were collected to identify the status of cortactin and HDAC6 by immunohistochemistry. Their correlation between clinicopathological characteristics and prognostic values were further analysed. The effect of cortactin and HDAC6 on prostate cancer cell migration and invasion was then evaluated in IA8 cells. The results showed that expression of cortactin and HDAC6 was significantly higher in PfCa foci, compared to that of high‐grade prostatic intraepithelial neoplasia (HGPIN) foci and benign foci (P < 0.05). Cortactin and HDAC6 were associated with poor prognosis of patients with PfCa (P < 0.05). Multivariable Cox regression analysis showed HDAC6 level was a significant prognostic factor for survival of patients with PfCa (β = 1.200, Wald value = 7.282, P = 0.007, 95% CI = 1.389–7.941, P < 0.01, β > 0). Both knocking down cortactin and inhibition of HDAC6 activity with tubacin reduced in vitro migration and invasion ability of IA8 cells substantially. Furthermore, HDAC6 has prognostic value for patients with PfCa. Dysregulation of cortactin and HDAC6 is implicated in the invasiveness and migration of prostate cancer cells.     

Apoptosis incidence and protein expression of p53, TGF-beta receptor II, p27Kip1, and Smad4 in benign, premalignant, and malignant human prostate

Deregulation of apoptosis is involved in prostate cancer development and progression. This study involved an immunohistochemical "profiling" of prostate tissue specimens from patients who underwent prostatectomy for localized prostate cancer, to identify apoptosis-specific alterations associated with premalignant precursor lesions. Prostate tissue was pathologically evaluated, and areas of benign acini, high-grade prostate intraepithelial neoplasia (HGPIN), and prostate cancer were identified. Immunohistochemical analysis was performed to determine the expression of p27Kip1, a key cell cycle regulator, transforming growth factor (TGF)-beta receptor II (TbetaRII), a critical signaling effector of TGF-beta; Smad4, a downstream intracellular effector of TGF-beta signaling; p53, a key apoptosis regulator; and prostate-specific antigen (PSA), a clinical marker of prostate cancer. The apoptotic index of the same cell populations was determined using the transferase-mediated digoxigenin-tagged 16-desoxy-uridine-triphosphate nick end labeling assay. Our findings indicate a significant reduction in p27Kip1 immunoreactivity in HGPIN (P<0.0001) and prostate cancer (P<0.0001) compared with the benign tissue. A significant down-regulation was detected in TbetaRII expression in HGPIN and prostate cancer compared with benign prostatic hyperplasia (BPH)(P<0.001). A significant decrease was also observed in Smad4 levels in HGPIN and prostate cancer compared with BPH (P<0.001). Evaluation of the incidence of apoptosis revealed a significant decrease in the apoptotic index among the epithelial cell populations in HGPIN and a further decrease in prostate carcinoma (P<0.01). This reduced apoptotic index correlated with a significant increase in p53 immunoreactivity in the prostatic carcinoma foci. Prostate cancer cells exhibited strong nuclear staining for p53 compared with adjacent HGPIN (P<0.05) and the benign lesions of the same prostate specimens (P<0.05). A significant reduction in PSA immunostaining was detected in HGPIN and prostate carcinoma foci compared with the benign glandular epithelia (P<0.001). These results further define deregulation of TGF-beta signaling effectors as a molecular basis for loss of apoptotic control contributing to the development of prostate tumors. Identification of apoptotic regulators in precursor premalignant lesions may have prognostic significance in disease progression as well as therapeutic value for targeting prostate cancer.     

The gene for polycomb group protein enhancer of zeste homolog 2 (EZH2) is amplified in late-stage prostate cancer

Overexpression of the polycomb group protein enhancer of zeste homologue 2 (EZH2) has been found in several malignancies, including prostate cancer, with an aggressive phenotype. Amplification of the gene has previously been demonstrated in several malignancies, but not in prostate cancer. Our goal was to evaluate the gene copy number and expression alterations of EZH2 in prostate cancer. The copy number of EZH2 in cell lines (LNCaP, DU145, PC‐3, 22Rv1), xenografts (n = 10), and clinical tumors (n = 191) was studied with fluorescence in situ hybridization. All cell lines had a gain of EZH2. Eight of the ten xenografts showed an increased copy number of the gene, including one case of high‐level amplification (≥5 copies of the gene and EZH2/centromere ratio ≥2). 34/125 (27%) of untreated prostate carcinomas showed increased copy number, but only one case of low‐level amplification (≥5 copies of the gene and EZH2/centromere ratio <2), whereas half (25/46) of the hormone‐refractory carcinomas showed increased copy number, including seven cases of low‐level amplification and three cases of high‐level amplification (P < 0.0001). Expression of EZH2 was significantly (P = 0.0009) higher in hormone‐refractory prostate cancer compared with that in benign prostatic hyperplasia or untreated cancer, according to quantitative real‐time RT‐PCR assay. Also, the expression of EZH2 protein was found to be higher in hormone‐refractory tumors than in hormone‐naïve tumors by immunohistochemistry. The EZH2 gene amplification was significantly (P < 0.05) associated with increased EZH2 protein expression. The data show that amplification of the EZH2 gene is rare in early prostate cancer, whereas a fraction of late‐stage tumors contains the gene amplification leading to the overexpression of the gene, thus indicating the importance of EZH2 in the progression of prostate cancer. © 2006 Wiley‐Liss, Inc.     

Upregulation of PTTG1 is associated with poor prognosis in prostate cancer

Pituitary tumor‐transforming gene 1 (PTTG1) is a regulator of chromosome stability. PTTG1 overexpression had been associated with tumor aggressiveness in several cancer types. To examine its prognostic utility in prostate cancer, a tissue microarray including 12 427 tumors with clinical and molecular data was analyzed by immunohistochemistry. PTTG1 immunostaining was largely absent in normal prostate epithelial cells. In cancers, staining was considered weak in 5.4%, moderate in 5.6% and strong in 0.8%. Strong staining was linked to advanced pT stage, high classical and quantitative Gleason grade, high Ki67‐labeling index (all P < 0.0001) and lymph node metastasis (P = 0.0083). The prognostic impact of PTTG1 expression was independent of established preoperative and postoperative prognostic features. Comparison with molecular features revealed that PTTG1 upregulation was associated with nine of 12 common genomic deletions (P < 0.05), p53 alterations and high androgen receptor levels (P < 0.001 each), but was unrelated to the TMPRSS2:ERG fusion status. In conclusion, these data identify PTTG1 as a strong and independent prognostic feature in prostate cancer. PTTG1 measurement, either alone or in combination with other biomarkers might be instrumental for determining prostate cancer aggressiveness.     

Glucose-regulated protein GRP78 is up-regulated in prostate cancer and correlates with recurrence and survival

Chemotherapy resistance is a significant contributor to treatment failure and death in men with hormone-refractory prostate cancer. One unexplored mechanism for drug resistance is the induction of stress response proteins referred to as the glucose-regulated proteins (GRPs). We sought to determine the level of expression of GRP78, the best characterized GRP in lymph node-positive prostate cancer. Archived, paraffin-embedded, radical prostatectomy specimens were obtained from 153 patients with lymph node-positive prostate cancer (stage D1). The level of GRP78 expression was determined by immunohistochemistry. We assessed the expression and specificity of GRP78 immunoreactivity in benign prostatic tissue, prostate cancer, and lymph node metastasis. We correlated the intensity of immunopositivity with prostate cancer recurrence and survival. Whereas immunohistochemical staining demonstrated that all prostate tissue was immunoreactive for GRP78, the intensity of expression was markedly higher in the primary tumor compared with areas of benign epithelium. GRP78 expression was also evident in lymph node metastases although less intensely than in the primary tumor. Patients with strong GRP78 immunoreactivity in the primary tumor are at higher risk for clinical recurrence (relative risk = 2.0, P = .019) and death (relative risk = 1.8, P = .024) than patients with weak GRP78 expression. This finding confirms that GRP78 protein expression is significantly higher in prostate cancer than in benign prostatic tissue. The intensity of expression is significantly associated with survival and clinical recurrence. GRP78 has considerable potential not only as a prognostic indicator but also as a potential therapeutic target.     

The role of secreted frizzled-related protein 2 expression in prostate cancer

O’Hurley G, Perry A S, O’Grady A, Loftus B, Smyth P, O’Leary J J, Sheils O, Fitzpatrick J M, Hewitt S M, Lawler M & Kay E W
(2011) Histopathology  59 , 1240–1248
The role of secreted frizzled‐related protein 2 expression in prostate cancer Aims: Improved prostate cancer (PCa)‐specific biomarkers are urgently required to distinguish between indolent and aggressive disease, in order to avoid overtreatment. In this study, we investigated the prostatic tissue expression of secreted frizzled‐related protein (SFRP)‐2. Methods and results: Following immunohistochemical analysis on PCa tissue microarrays with samples from 216 patients, strong/moderate SFRP‐2 expression was observed in epithelial cells of benign prostatic hyperplasia, and negative/weak SFRP‐2 expression was observed in the majority of tumour epithelia. However, among Gleason grade 5 carcinomas, 40% showed strong/moderate SFRP‐2 expression and 60% showed negative SFRP‐2 expression in epithelial cells. Further microscopic evaluation of Gleason grade 5 tumours revealed different morphological patterns, corresponding with differential SFRP‐2 expression. The first subgroup (referred to as Type A) appeared to have a morphologically solid growth pattern, whereas the second subgroup (referred to as Type B) appeared to have a more diffuse pattern. Furthermore, 100% (4/4) of Type A patients experienced biochemical recurrence, as compared with 0% (0/6) of Type B patients. Conclusions: These results imply: (i) that there is a loss of SFRP‐2 expression from benign to malignant prostate glands; and (ii) differential SFRP‐2 expression among two possible subgroups of Gleason grade 5 tumours.     

Expression of the extracellular matrix protein periostin in liver tumours and bile duct carcinomas

Riener M‐O, Fritzsche F R, Soll C, Pestalozzi B C, Probst‐Hensch N, Clavien P‐Alain, Jochum W, Soltermann A, Moch H & Kristiansen G
(2010) Histopathology 56 , 600–606 Expression of the extracellular matrix protein periostin in liver tumours and bile duct carcinomas Aims: To study the relevance of periostin, known to be involved in epithelial–mesenchymal transition (EMT), in hepatocellular and bile duct cancer. Methods and results: Immunohistochemical periostin expression was semiquantitatively analysed in normal liver tissue (n = 20), hepatocellular carcinoma (HCC; n = 91), liver‐cell adenoma (n = 9), focal nodular hyperplasia (n = 13) and bile duct carcinomas (BDC; n = 116) using tissue microarrays. Normal bile ducts, gallbladder epithelium and hepatocytes showed weak cytoplasmic periostin expression. In HCC, there was strong epithelial periostin expression in 19/91 (20.9%) and strong stromal periostin expression in 10/91 cases (11%). Epithelial expression in tumour cells was significantly associated with a higher tumour grade (P < 0.05) and hepatitis B virus infection (P = 0.007). Importantly, there was no strong periostin expression in benign liver tumours. Strong stromal periostin expression was detected in 78/116 (67.2%) BDC and strong epithelial expression in 39/116 (33.6%) BDC. pT stage, differentiation grade and proliferation rate in primary BDC were independent of periostin expression. Epithelial periostin expression was associated with reduced overall survival on univariate and multivariate analysis. Conclusions: The EMT protein periostin is expressed in the stroma and epithelium of a subset of BDC and HCC. Epithelial periostin expression is a marker for malignant transformation of hepatocytes and a novel prognostic marker in BDC.     

Evidence for distinct alterations in the FGF axis in prostate cancer progression to an aggressive clinical phenotype

Multiple fibroblast growth factor (FGF) axis alterations are known to occur in prostate cancer. Here we simultaneously profiled key components of this axis to determine their relevance in disease progression. An optimized immunohistochemistry protocol was used in expression analysis of FGF2, FGF8, FGFR1, FGFR4, and Sef (similar expression to FGF) in a single TMA of prostate cancer. FGF ligands and receptors were overexpressed in cancers compared to benign samples (p < 0.0001), while Sef expression was reduced (p < 0.0001). There was a positive association between higher grades and increased FGFR4 (p = 0.02), FGF2, and FGF8 (p = 0.002 and p < 0.0001). Sef expression was progressively lower with increasing grade (p = 0.005). Clinical stage was positively associated with FGF2, FGF8, and FGFR4 expression (p = 0.005, 0.03, and 0.012) but not with FGFR1 or Sef expression. Only reduced Sef was associated with bone metastasis (p = 0.02) and was also predictive of subsequent metastasis in initially localized tumours (p = 0.004). Down‐regulation of Sef and increased FGFR4 were also the only independent variables associated with disease‐specific survival (HR 1.73, p = 0.04 and HR 0.56, p = 0.01). In in vitro studies, silencing Sef enhanced the cell response to FGFs (p < 0.001) and substantially mitigated the effectiveness of an FGFR1 inhibitor. Conversely, increased Sef blocked the response to FGFs and had a comparable suppressive effect to the inhibitor. This study demonstrates that increased FGFR4 and reduced Sef may be critical FGF alterations associated with prostate cancer progression. Sef may also have a role in the tumour response to FGFR inhibition and warrants further investigation in this context. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Prognostic Value of Prostaglandin-endoperoxide Synthase 2 Polymorphisms in Prostate Cancer Recurrence after Radical Prostatectomy

Backgroud: Increasing evidence suggests the involvement of chronic inflammation in the progression of prostate cancer, and prostaglandin-endoperoxide synthase 2 (PTGS2), also known as cyclooxygenase-2, catalyzes the rate-limiting steps of the pathway. We hypothesized that genetic variants of PTGS2 can influence the outcome of prostate cancer patients.Methods: We genotyped five haplotype-tagging single-nucleotide polymorphisms (SNPs) to detect common genetic variations across the PTGS2 region in 458 prostate cancer patients treated with radical prostatectomy.Results: One SNP, rs4648302, was associated with disease recurrence. Five-year recurrence-free survival rate increased according to the number of variant alleles inherited (55.6%, 70.7%, and 100.0% for patients with different genotypes; P = 0.037), and the effect was maintained in multivariable analysis. Public dataset analyses also suggested that PTGS2 expression was correlated with prostate cancer prognosis.Conclusion: Our results indicated that PTGS2 could be a potential prognostic marker to improve the prediction of disease recurrence in prostate cancer patients.