Aberrant expression of nuclear vimentin and related epithelial-mesenchymal transition markers in nasopharyngeal carcinoma

Expression of vimentin and the epithelial to mesenchymal transition (EMT) markers E-cadherin, β-catenin is essential for the progression of various human cancers. Our study aimed to investigate the aberrant localization E-cadherin, β-catenin and vimentin, and their prognostic significance in 122 nasopharyngeal carcinoma (NPC) patients by immunohistochemistry and immunofluorescence. Our results showed that both membranous and cytoplasmic localization of E-cadherin staining were associated with lymph node metastasis (p = 0.000 and 0.005, respectively) and clinical stage (p = 0.000 and 0.007, respectively). High cytoplasmic β-catenin correlated significantly with larger tumor size (p = 0.020), lymph node metastasis (p = 0.000) and advanced clinical stage (p = 0.036). However, no significant difference was observed between membranous β-catenin and clinicopathologic features (p ≥ 0.05). High nuclear vimentin expression correlated significantly with positive lymph node metastasis (p = 0.000) and advanced clinical stage (p = 0.000). Multivariate analysis showed that nuclear vimentin and cytoplasmic E-cadherin were independent prognostic factors (p = 0.016 and 0.001, respectively), as well as M classification (p = 0.001). More importantly, patients with high coexpression of nuclear vimentin and cytoplasmic E-cadherin had shorter survival time (p = 0.000). Furthermore, high coexpression of these two proteins was closely associated with lymph node metastasis (p = 0.000) and advanced clinical stage (p = 0.000). Our studies provide convincing evidence that EMT may play an important role in the biological progression of NPC, and nuclear vimentin and cytoplasmic E-cadherin might have independent prognostic value in NPC patients and serve as novel targets for prognostic therapeutics.     

Prognostic markers in clinically localised prostate cancer

The prognostic value of immunohistochemical staining of P53, BCL-2, p27kip1, PSA, AR and MIB-1 was compared with that of established prognostic variables (Gleason score, surgical margins, tumour volume) following radical prostatectomy. Five groups were selected: negative margins with stable serum PSA (n=11), negative margins with rising serum PSA (n=7), positive margins with stable serum PSA (n=7), positive margins with rising serum PSA (6) and patients with micrometastatic disease diagnosed in lymph nodes removed during radical prostatectomy (n=8). Gleason score and tumour volume were of prognostic significance and immunohistochemical staining for MIB-1 and BCL-2 showed added independent prognostic significance in multivariate analysis.     

Expression of p21 predicts PSA failure in locally advanced prostate cancer treated by prostatectomy

The management of prostate cancer is based on several clinicopathological criteria. The ability to determine the tumor's biological potential is one goal of tumor markers in order to identify patients who may require more intensive treatment strategies. The purpose of our study was to determine if p21/(WAF1/CIP1) expression can predict biochemical failure in patients with locally advanced prostate cancer treated by radical retropubic prostatectomy (RRP). We used immunohistochemistry to analyze patterns of p21 expression in a population of 296 patients with locally advanced (pT3) prostate cancer treated by RRP. Results were correlated with clinicopathological parameters and time to PSA failure. For the entire cohort of 296 patients, after adjustment for prognostic factors, p21 expression was associated with an increased risk of PSA failure (relative risk [RR] = 1.48) of statistical significance at a median follow-up of 54.5 months. Other parameters that independently predicted the risk of PSA failure included lymph node metastasis and seminal vesicle involvement. Because neoadjuvant hormonal therapy (NHT) is known to lead to involutional changes in prostatic carcinoma, we performed multivariate analyses after stratifying for NHT prior to surgery. Among the 172 patients treated by RRP alone, p21 expression was an independent predictor of PSA failure (RR = 2.30), as were lymph node metastases (RR = 3.19) and pathological grade 5-7 and 8-10 (RR = 2.87 and 3.50, respectively). p21 over-expression is an independent predictor of PSA failure in pT3 patients treated by radical prostatectomy, especially if they did not receive NHT. This tumor marker may help clinicians identify patients who may require adjuvant treatment strategies following radical prostatectomy.     

Tumor volume changes on 1.5 tesla endorectal MRI during neoadjuvant androgen suppression therapy for higher-risk prostate cancer and recurrence in men treated using radiation therapy results of the phase II CALGB 9682 study

PURPOSE: We prospectively determined whether the change in tumor volume (TV) during 2 months of neoadjuvant androgen suppression therapy (nAST) measured using conventional 1.5 Tesla endorectal magnetic resonance imaging (eMRI) was associated with the risk of recurrence after radiation (RT) and 6 months of AST. PATIENTS AND METHODS: Between 1997 and 2001, 180 men with clinical stage T1c-T3cN0M0 adenocarcinoma of the prostate were registered. Fifteen were found to be ineligible and the institutional MR radiologist could not assess the TV in 32, leaving 133 for analysis. Multivariable Cox regression analysis was used to assess whether a significant association existed between eMRI-defined TV progression during nAST and time to recurrence adjusting for prostate-specific antigen (PSA) level, Gleason score (8 to 10 or 7 vs. 6 or less) and stage (T3 vs. T1-2). RESULTS: After a median follow up of 6.7 years and adjusting for known prognostic factors, there was a significant increase in the risk of PSA failure (HR, 2.3 [95% CI, 1.1-4.5; p = 0.025) in men with eMRI-defined TV progression during nAST. Specifically, adjusted estimates of PSA failure were significantly higher (p = 0.032) in men with, compared with men without, eMRI-defined TV progression reaching 38% vs. 19%, respectively, by 5 years. CONCLUSION: Eradicating intraprostatic hormone refractory prostate cancer (HRPC) by maximizing local control and randomized trials assessing whether survival is improved when agents active against HRPC are combined with maximal local therapy are needed in men who progress based on eMRI during nAST.     

Quantifying the impact of seminal vesicle invasion identified using endorectal magnetic resonance imaging on PSA outcome after radiation therapy for patients with clinically localized prostate cancer

PURPOSE: This study examined the impact that seminal vesicle invasion (SVI), observed on endorectal magnetic resonance imaging (erMRI), had on prostate-specific antigen (PSA) outcome after external beam radiation therapy (EBRT) for patients with clinically localized prostate cancer. METHODS AND MATERIALS: The study cohort was comprised of 250 patients who received 3D conformal radiation therapy without hormones for clinically localized prostate cancer between 1992 and 2001. The primary end point was PSA failure, defined using the American Society for Therapeutic Radiology and Oncology consensus definition. Cox regression multivariable analysis was used to determine the ability of the pretreatment risk group and erMRI SVI to predict for time to PSA failure after EBRT. RESULTS: Both risk group (p(Cox) = 0.001) and erMRI SVI (p(Cox) = 0.003) were independent and significant predictors of time to PSA failure. For patients beyond low risk, 4-year estimates of PSA failure-free survival for erMRI SVI-negative vs. erMRI SVI-positive patients were 68% vs. 33% (p(log-rank) = 0.0014), respectively. CONCLUSION: Patients with clinically localized disease and PSA >10 or biopsy Gleason score >or=7 or clinical T category T2b or T2c who also have erMRI evidence of SVI have PSA outcomes similar to patients with locally advanced prostate cancer after EBRT monotherapy. Consideration should be given to combining EBRT with hormonal therapy in these patients.     

Survivin在乳腺癌组织中的表达及其临床意义

目的:探讨Survivin在乳腺癌组织中的表达与凋亡指数(apoptosis index,AI)以及临床指标的相关性和预后的意义。方法:免疫组化法检测63例乳腺癌标本中Survivin的表达;TUNEL法检测乳腺癌组织中的AI。结果:Survivin在乳腺癌组织中的表达阳性率为63·5%。Survivin与AI呈负相关,P=0·0000。Survivin与肿块直径、肿瘤分期、雌激素受体状态无关,而与腋窝淋巴结转移呈正相关,P=0·0000。单因素分析显示,Survivin是乳腺癌的一个预后指标,P=0·0115。结论:Survivin是一种有效的凋亡抑制蛋白,在肿瘤的发生过程中起一定作用。检测Survivin对乳腺癌的预后分析和进一步治疗具有指导作用。肿瘤防治杂志,2005,12(19):1476-1479     

Lower levels of nuclear beta-catenin predict for a poorer prognosis in localized prostate cancer

Beta-catenin in its role as a nuclear signaling molecule has been implicated in prostate carcinogenesis primarily through modulation of androgen receptor activity. We defined the pattern of beta-catenin protein expression in the nuclei of normal, hyperplastic and malignant human prostate tissue and determined whether differences in expression were associated with disease progression and prognosis. Five normal prostates, 26 benign prostatic hypertrophy specimens, 232 radical prostatectomy specimens from patients with clinically localized prostate cancer (PC) and 20 cases of advanced PC were assessed for beta-catenin expression using immunohistochemistry. Nuclear beta-catenin expression in localized PC was significantly lower than that in benign prostate tissue (p < 0.001) and significantly higher than that in advanced PC tissue (p < 0.001). In addition, lower levels of nuclear beta-catenin expression (< 10% of cancer cells) predicted for a shorter biochemical relapse-free survival in patients with localized PC (p = 0.008) and were inversely correlated with preoperative prostate-specific antigen (PSA) levels (p = 0.01). Analysis of the low-risk subgroup of patients with preoperative PSA levels < 10 ng/ml demonstrated that lower levels of nuclear beta-catenin expression (< 10% of cancer cells) again predicted for a poorer prognosis (p = 0.006). In conclusion, lower levels of nuclear beta-catenin expression are found in malignant compared to benign prostate tissue. In addition, lower nuclear beta-catenin expression is associated with a poorer prognosis in localized PC, in particular, in the low-risk subgroup of patients with preoperative PSA levels < 10 ng/ml. Thus, the level of nuclear beta-catenin expression may be of clinical utility as a preoperative prognostic marker in low-risk localized PC.     

Expression of annexin A1 in esophageal and esophagogastric junction adenocarcinomas: association with poor outcome.

PURPOSE: Annexin A1 (ANXA1) is a calcium-binding protein involved in arachidonic acid metabolism and epidermal growth factor receptor tyrosine kinase pathway. ANXA1 has been implicated in early squamous cell carcinogenesis of esophagus and correlates with degree of tumor differentiation. However, the role of ANXA1 in esophageal adenocarcinoma is unclear. Our goal was to evaluate ANXA1 expression and determine its prognostic significance in adenocarcinoma of the esophagus and esophagogastric junction. EXPERIMENTAL DESIGN: This study included 104 consecutive patients with primary resected esophageal and esophagogastric junction adenocarcinomas (11 stage I, 24 stage II, 53 stage III, and 16 stage IV). ANXA1 protein expression in each tumor was assessed by immunohistochemical staining of tissue microarrays. ANAX1 expression level was classified as high (>/=25% of tumor cells with cytoplasmic staining), low (<25% of tumor cells with cytoplasmic staining), or negative; and was correlated with clinicopathologic features and patients' outcomes. RESULTS: High ANXA1 expression was present in 39% (41 of 104) of tumors and was associated with higher pathologic T stage (P = 0.03) and distant metastasis (P = 0.04). High ANXA1 expression correlated with increased recurrence rate (P = 0.004) and decreased overall survival (P = 0.003) in univariate analysis. In multivariate analysis, ANXA1 expression and pN stage significantly correlated with recurrence rate (P = 0.008 and P < 0.001, respectively) and overall survival (P = 0.02 and P < 0.001, respectively) independent of T stage. CONCLUSION: Our results indicate that high ANXA1 expression is frequent in esophageal and esophagogastric junction adenocarcinomas, correlates with more advanced pathologic T stage and the presence of distant metastasis, and is an independent prognostic factor for patient survival.     

胃癌腹膜转移相关基因 MYH-9与胃癌转移及其预后的关系

目的：研究胃癌腹膜转移相关基因MYH-9与胃癌转移及预后的关系。方法50例组织标本取自手术切除的胃癌组织及同一患者的腹膜转移组织标本。组织固定在10％的缓冲甲醛溶液用于病理诊断,冷冻于液氮中备于免疫印迹分析、细胞培养、siRNA转染、细胞粘附实验。结果 MYH-9在所有的鳞状细胞癌组织（100％）和8个邻近正常组织中表达（26．7％,P＝0．000）。癌组织中MYH-9高表达水平与腹膜转移、肿瘤分化程度差和较晚的肿瘤分期显著相关。单变量分析结果显示：肿瘤分期、胃癌病灶是否切除、腹膜转移的存在、MYH9高表达（基于免疫组化染色）与患者总生存率显著相关（P＝0．008、P＝0．001、P＝0．006和P＝0．007）。进一步的多因素回归分析显示,肿瘤分期与MYH-9高表达是与总生存期相关的独立不良预后因素。结论 MYH-9的过度表达可能与较高的癌细胞迁移性相关。     

PTTG、bFGF、VEGF-C在大肠正常黏膜及大肠癌中的表达及意义

探讨垂体肿瘤转化基因（PTTG）、碱性成纤维细胞生长因子（bFGF）、血管内皮生长因子-C（VEGF-C）在大肠癌中的表达及以上指标与大肠癌临床病理因素之间的关系。方法:采用RT-PCR技术检测20例大肠正常黏膜、80例大肠癌组织中PTTG mRNA,应用免疫组织化学法检测20例大肠正常黏膜、80例大肠癌组织中PTTG、bFGF、VEGF-C蛋白的表达。结果:大肠癌组织中PTTG、bFGF、VEGF-C的表达明显高于大肠正常黏膜组织,且与大肠癌浸润深度、淋巴结转移、Duke's分期呈正相关,PTTG、bFGF、VEGF-C在大肠癌中的表达有显著正相关性。结论:PTTG、bFGF、VEGF-C在大肠癌发生、发展、侵袭及转移过程中扮演着重要的角色,可作为判断大肠癌转移及预后的预测因素,且三者可能通过相互作用共同促进大肠癌的恶性进展。      

Excision repair cross complementation group 1 immunohistochemical expression predicts objective response and cancer-specific survival in patients treated by Cisplatin-based induction chemotherapy for locally advanced head and neck squamous cell carcinoma.

PURPOSE: To assess the correlation of excision repair cross complementation group 1 (ERCC1) immunohistochemical expression with objective tumor response and cancer-specific survival in patients with locally advanced head and neck squamous cell carcinoma treated with cisplatin-based induction chemotherapy. EXPERIMENTAL DESIGN: The initial cohort was composed of 107 patients who were treated from 1992 to 1996 by an induction chemotherapy regimen for locally advanced head and neck squamous cell carcinoma. p53 mutations had previously been studied. Pretherapeutic biopsy samples from 96 patients with a known tumor response were available. Two independent observers blinded to clinical annotations evaluated ERCC1 immunohistochemical expression. RESULTS: Of 96 patients, 68 (71%; 95% confidence interval, 61-79%) had tumors that expressed ERCC1 intensively and diffusely. Using the logistic regression method, the 28 (29%) patients with tumors expressing ERCC1 at lower levels had a 4-fold greater odds of benefiting from an objective response to chemotherapy (odds ratio, 4.3; 95% confidence interval, 1.4-13.4; P = 0.01) compared with the group of 68 patients with high ERCC1 expression. ERCC1 and p53 status, but not their interaction, were independent predictors of tumor response. In a Cox proportional hazard model adjusted on age, TNM stage, tumor differentiation, and tumor localization, ERCC1 low expression was associated with a lower risk of cancer death (risk ratio, 0.42; 95% confidence interval, 0.20-0.90; P = 0.04) whereas p53 status had no prognostic value. CONCLUSION: Our results suggest that those patients characterized by low ERCC1 expression are more likely to benefit from cisplatin induction chemotherapy compared with patients with high ERCC1 expression.     

Overexpression of MDM2 and p53 protein is infrequently but significantly associated with progression of human prostatic adenocarcinoma

In the present immunohistochemical study using anti-p53 (DO-7) and anti-MDM2 (IF2) antibodies, we determined the frequency of p53 and MDM2 protein expression in a series of 115 primary prostatic adenocarcinomas (stage A1 to D2) and evaluated the reliability of p53 and MDM2 immunoreactivity as an indicator for tumor progression. Overall, 13.9% (16/115) of surgically resected tumors were positive for anti-p53 antibody. A significantly higher association of immunoreactivity for p53 was detected in both high-grade (4/16, 25%; p<0.05) and advanced stage tumors (14/73, 19.1%; p<0.05) compared with that of other grade or stage. Positive staining for anti-MDM2 antibody was observed in only 4.3% (5/115) of the tumors examined. However, nuclear MDM2 protein overexpression, detected as focal and markedly heterogeneous staining, was sometimes observed especially in advanced stage tumors (4 stage C and 1 stage D tumors), and was significantly more common in locally advanced cancers (p<0.05) than in those of other stage. Only 2 cases (1.7%) exhibited positive staining with both p53 and MDM2 antibodies. These findings suggest that p53 and MDM2 alterations might play significant roles in the development and progression of some advanced stage or high-grade prostatic cancers, although MDM2 and p53 protein overexpression is infrequent in prostatic adenocarcinoma.     

Clinical utility of endorectal MRI in determining PSA outcome for patients with biopsy Gleason score 7, PSA <or=10, and clinically localized prostate cancer

PURPOSE: Although the optimal management for patients with high-grade clinically localized prostate cancer is undefined, radical prostatectomy (RP) or external beam radiotherapy (EBRT) is performed. The clinical utility of the pretreatment prostrate-specific antigen (PSA) level (10 ng/mL) and endorectal MRI (erMRI) stage (T3 vs. T2) to stratify PSA outcome after RP in these patients was evaluated. METHODS AND MATERIALS: erMRI was performed in 147 men with biopsy Gleason score >or=7 and 1992 AJCC clinical Stage T1c or T2a disease before RP. Enumerations of the biopsy and prostatectomy Gleason scores, pathologic stage, and margin status were performed for each pretreatment group on the basis of erMRI findings and PSA level. Comparisons were made using a chi-square metric. The median follow-up was 4.5 years (range 1-10 years). Comparisons of the actuarial freedom from PSA failure (bNED) were made using the log-rank test. RESULTS: erMRI Stage T2 and T3 disease was found in 132 and 15 patients, respectively. On stratification by PSA level, patients with erMRI T3 disease had similar bNED outcomes (p = 0.46), regardless of the PSA level. The 3-year bNED rate was 82%, 64%, and 25% (p <0.0001) for Group 1 (erMRI T2 and PSA 10 ng/mL), and Group 3 (erMRI T3 with any PSA level), respectively. The rates of prostatectomy T3 disease, biopsy and prostatectomy Gleason score 8-10, and positive surgical margins were significantly higher (p or=7, PSA 相似文献   

Differential expression of the mismatch repair gene hMSH2 in malignant prostate tissue is associated with cancer recurrence

BACKGROUND: Mismatch repair (MMR) genes are responsible for coordinated correction of misincorporated nucleotides formed during DNA replication. Inactivating mutations in MMR genes have been described in sporadic cancers and a hereditary cancer predisposition syndrome. Mismatch repair deficiency causes instability at microsatellites and increased mutation rates. Although microsatellite instability (MSI) has been described in high-grade and lymph node positive prostate carcinoma specimens, an analysis comparing hMSH2 expression, MSI, and outcome in clinically organ confined prostate carcinoma has not been reported. METHODS: Immunohistochemical analysis of benign and malignant prostate tissue from 101 patients was performed using a monoclonal antibody specific for the hMSH2 protein. Expression was correlated with MSI using dinucleotide repeat markers and laser-captured microdissected DNA from normal and tumor cells. hMSH2 protein expression and MSI were assessed with respect to pathologic stage, Gleason score, and time to detectable serum prostate specific antigen (PSA) after prostatectomy in patients with clinically localized prostate carcinoma. RESULTS: In normal glands, hMSH2 staining was minimal to low and confined to the basal cell layer. In 32% of benign prostatic hyperplasia cases, hMSH2 staining was increased in the basal and luminal cell layers whereas 71% of cancer specimens had uniform moderate to high staining. Microsatellite instability was detected in 60% of absent to low staining and 26% of moderate to high staining prostate carcinoma specimens. Differential staining in benign versus malignant prostate tissues was statistically significant (P < 0.001) as was the correlation between absent to low hMSH2 staining and presence of MSI (P = 0.028). Decreased risk for PSA recurrence after radical prostatectomy correlated with absent to low hMSH2 staining in malignant prostate tissue but was only marginally significant (P = 0.05 for 24 month recurrence and P = 0.08 for overall time to PSA recurrence). CONCLUSIONS: The results of the current study demonstrate differential hMSH2 expression in benign and malignant prostate tissue. Moreover, hMSH2 expression is altered in a subset of clinically localized prostate carcinoma specimens independent of pathologic stage and Gleason pattern. A statistically significant correlation between hMSH2 immunohistochemical staining intensity and MSI also was identified in prostate carcinoma specimens. Furthermore, the time to cancer recurrence as determined by detectable serum PSA after prostatectomy was associated with hMSH2 staining intensity. Taken together, our results suggest that hMSH2 gene expression in prostate carcinoma may be a useful prognostic marker for outcome in men with clinically organ confined prostate carcinoma.     

Independent prognostic significance of HER-2 oncoprotein expression in pN0 prostate cancer undergoing curative radiotherapy

Existing prognostic algorithms for localized prostate cancer (PC) are hampered by poor validation for endpoints other than biochemical relapse such as clinical disease progression or survival. Therefore, the prognostic relevance of Her-2 (Her-2/neu, c-erbB2) protein expression in patients undergoing curative radiotherapy (RT) was compared to widely accepted prognostic factors such as pretreatment prostate-specific antigen (PSA) levels, biopsy Gleason score and T category of the primary tumor. Biopsies from 112 homogeneously treated patients with T1-4pN0M0 PC were examined by immunohistochemistry and 37% of cases showed membrane-bound Her-2 expression in more than 10% of cancer cells. No definite membrane staining was seen in normal prostate epithelium. With 25 patients dead of PC and a median follow-up of surviving patients of 71 months (range 48-144), the prognostic relevance of Her-2 expression was univariately associated with adverse outcome in terms of biochemical or clinical progression-free survival (B/C-PFS; p = 0.04), clinical progression-free survival (C-PFS; p = 0.02) and disease-specific survival (DSS; p = 0.02). In multivariate analysis, Her-2 expression, T category and Gleason score were independently associated with C-PFS, whereas only Her-2 expression and Gleason score were associated with DSS. Her-2 expression and Gleason score together discriminated 2 groups of patients with 5-year DSS of 95% and 79%, respectively (p < 0.001). Pretreatment PSA levels were associated only with B/C-PFS but not with C-PFS or DSS. Together the data show for the first time that expression of Her-2 is of prognostic relevance in localized PC undergoing RT and suggest that analysis for Her-2 may improve prognostic algorithms for clinically relevant endpoints other than biochemical relapse.     

p53 and Cyclooxygenase-2 Expression are Directly Associated with Cyclin D1 Expression in Radical Prostatectomy Specimens of Patients with Hormone-Naïve Prostate Cancer

Prostate cancer (PCa) is a potentially curable disease when diagnosed in early stages and subsequently treated with radical prostatectomy (RP). However, a significant proportion of patients tend to relapse early, with the emergence of biochemical failure (BF) as an established precursor of progression to metastatic disease. Several candidate molecular markers have been studied in an effort to enhance the accuracy of existing predictive tools regarding the risk of BF after RP. We studied the immunohistochemical expression of p53, cyclooxygenase-2 (COX-2) and cyclin D1 in a cohort of 70 patients that underwent RP for early stage, hormone naïve PCa, with the aim of prospectively identifying any possible interrelations as well as correlations with known prognostic parameters such as Gleason score, pathological stage and time to prostate-specific antigen (PSA) relapse. We observed a significant (p?=?0.003) prognostic role of p53, with high protein expression correlating with shorter time to BF (TTBF) in univariate analysis. Both p53 and COX-2 expression were directly associated with cyclin D1 expression (p?=?0.055 and p?=?0.050 respectively). High p53 expression was also found to be an independent prognostic factor (p?=?0.023). Based on previous data and results provided by this study, p53 expression exerts an independent negative prognostic role in localized prostate cancer and could therefore be evaluated as a useful new molecular marker to be added in the set of known prognostic indicators of the disease. With respect to COX-2 and cyclin D1, further studies are required to elucidate their role in early prediction of PCa relapse after RP.     

Prediction by quantitative histology of pathological stage in prostate cancer.

AIMS: To find a predictor of extraprostatic extension in clinically localized prostate cancer (PCa), pre-operative ultrasound-guided prostate needle biopsies and clinico-pathological data were reviewed. METHODS: One hundred and eighty-three consecutive patients who underwent radical retropubic prostatectomy for clinical T1-T2 PCa and serum PSA <10 ng/ml were reviewed. Pre-operative biopsy was performed according to an extended protocol and whole-mount prostatectomy specimens were processed. The following biopsy variables were categorized to this analysis: Gleason score (< or =6, >6), TPC (< or =20%; >20%), GPC (< or =50%; >50%), cancer-positive cores (< or =2; >2), cancer-positive cores in both lateral portions (yes; no), PCa (monolateral; bilateral). RESULTS: Only 60/183 specimens showed an organ-confined PCa; the remaining ones showed pT3a in 57 cases, pT3b in 11 and pT3 with positive surgical margins in 55. A locally advanced PCa was found in 60.2 and 76.8% of T1c and T2 clinical stage, respectively. The positive predictive value and negative predictive value of biopsy findings to predict a locally advanced PCa was 89.9 and 75%, respectively. All biopsy variables associations were statistically significant; however, among these variables (non-categorized), in multivariate logistic regression analysis, only GPC was significantly associated with pathologic stage (odds ratio estimate was 1.075, 95% CI: 1.053-1.098). CONCLUSIONS: Quantitative histology, especially GPC, seems to be helpful for pre-operative staging of PCa in patients with T1c-T2 clinical stage and PSA < 10 ng/ml.     

Cyclooxygenase-2 (COX-2) expression is an independent predictor of prostate cancer recurrence

Lack of reliable prognostic markers hinders accurate prediction of disease progression in prostate cancer. The inducible proinflammatory enzyme cyclooxygenase-2 (COX-2) is implicated in prostate carcinogenesis, but its role in cancer progression is less clear. We examined whether COX-2 expression evaluated by immunohistochemistry (IHC) in radical prostatectomy (RP) specimens can predict biochemical recurrence. Archival prostate cancer specimens (n = 60) were obtained from patients who underwent RP, but had not received neoadjuvant hormonal therapy. Twenty-three patients had biochemical or clinical recurrence (mean time of recurrence: 38.2 months), and 37 patients were recurrence free (mean follow-up: 95 months). COX-2 expression was determined by IHC, using an anti-COX-2 antibody. Three individuals scored the staining independently, as high- or low-expression. COX-2 was expressed in prostate cancer cells, in adjacent normal glands and in specimens from patients who later progressed. At 62-months follow-up, COX-2 staining predicted progression with 82.4% sensitivity and 81.3% specificity. Sensitivity (86.4%) and specificity (86.7%) improved at > or = 100-months follow-up. In univariate analysis, Gleason score, preoperative PSA, extraprostatic extension, margin, seminal vesicle invasion, and high COX-2 expression were significant predictors of biochemical recurrence (p < 0.05). In multivariate analysis, preoperative PSA (hazard ratio/unit PSA change 1.080; p = 0.0036) and COX-2 expression (hazard ratio 16.442; p < 0.0001) were independent prognostic indicators. Patients with PSA > 7 ng/ml and high COX-2 expression had the highest probability of recurrence (Kaplan-Meier analysis). COX-2 expression is an independent predictor of prostate cancer progression following RP and underscores the significance of inflammatory factors in this process.