Immunoreactivity for prostate specific antigen and Ki67 differentiates subgroups of prostate cancer related to outcome.

Based on gene-expression profiles, prostate tumors can be subdivided into subtypes with different aggressiveness and response to treatment. We investigated if similar clinically relevant subgroups can be identified simply by the combination of two immunohistochemistry markers: one for tumor cell differentiation (prostate specific antigen, PSA) and one for proliferation (Ki67). This was analyzed in men with prostate cancer diagnosed at transurethral resection of the prostate 1975-1991 (n = 331) where the majority was managed by watchful waiting.

High Caveolin-1 Expression in Tumor Stroma Is Associated with a Favourable Outcome in Prostate Cancer Patients Managed by Watchful Waiting.

In the present study we have investigated whether Caveolin-1 expression in non-malignant and malignant prostate tissue is a potential prognostic marker for outcome in prostate cancer patients managed by watchful waiting. Caveolin-1 was measured in prostate tissues obtained through transurethral resection of the prostate from 395 patients diagnosed with prostate cancer. The majority of the patients (n = 298) were followed by watchful waiting after diagnosis.

Castration radiosensitizes prostate cancer tissue by impairing DNA double-strand break repair.

Chemical castration improves responses to radiotherapy in prostate cancer, but the mechanism is unknown. We hypothesized that this radiosensitization is caused by castration-mediated down-regulation of nonhomologous end joining (NHEJ) repair of DNA double-strand breaks (DSBs). To test this, we enrolled 48 patients with localized prostate cancer in two arms of the study: either radiotherapy first or radiotherapy after neoadjuvant castration treatment.

High Lysyl Oxidase (LOX) in the Non-Malignant Prostate Epithelium Predicts a Poor Outcome in Prostate Cancer Patient Managed by Watchful Waiting.

Lysyl oxidase (LOX) has been shown to both promote and suppress tumor progression, but its role in prostate cancer is largely unknown. LOX immunoreactivity was scored in prostate tumor epithelium, tumor stroma and in the tumor-adjacent non-malignant prostate epithelium and stroma. LOX scores in tumor and non-malignant prostate tissues were then examined for possible associations with clinical characteristics and survival in a historical cohort of men that were diagnosed with prostate cancer at transurethral resection and followed by watchful waiting.

Improving the Specificity of Screening for Lethal Prostate Cancer Using Prostate-specific Antigen and a Panel of Kallikrein Markers: A Nested Case-Control Study.

Background: A disadvantage of prostate-specific antigen (PSA) for the early detection of prostate cancer (PCa) is that many men must be screened, biopsied, and diagnosed to prevent one death.

Objective: To increase the specificity of screening for lethal PCa at an early stage.

Design, Setting, And Participants: We conducted a case-control study nested within a population-based cohort.

ErbB2 receptor immunoreactivity in prostate cancer: relationship to the androgen receptor, disease severity at diagnosis and disease outcome.

Background: ErbB2 is a member of the epidermal growth factor family of tyrosine kinases that is centrally involved in the pathogenesis of prostate cancer and several studies have reported that a high expression of this protein has prognostic value. In the present study, we have investigated whether tumour ErbB2 immunoreactivity (ErbB2-IR) has clinically useful prognostic value, i.e.

High density of S100A9 positive inflammatory cells in prostate cancer stroma is associated with poor outcome.

Purpose: To elucidate if the density of inflammatory cells expressing S100A9 in malignant and surrounding non-malignant prostate tissues is a prognostic marker for outcome in prostate cancer patients.

Experimental Design: Tissue was obtained from 358 men diagnosed with prostate cancer at transurethral resection of the prostate due to obstructive voiding problems, of which 260 were then followed with watchful waiting. Tissue microarrays of both malignant and non-malignant tissues were stained with an antibody against S100A9.

TMPRSS2-ERG expression predicts prostate cancer survival and associates with stromal biomarkers.

The TMPRSS2-ERG gene fusion is found in approximately half of all prostate cancers. The functional and prognostic significance of TMPRSS2-ERG is, however, not fully understood. Based on a historical watchful waiting cohort, an association between TMPRSS2-ERG, evaluated as positive immune staining, and shorter survival of prostate cancer patients was identified.

Castration therapy results in decreased Ku70 levels in prostate cancer.

Purpose: Neoadjuvant castration improves response to radiotherapy of prostate cancer. Here, we determine whether castration therapy impairs nonhomologous end-joining (NHEJ) repair of DNA double-strand breaks (DSB) by downregulating Ku70 protein expression.

Experimental Design: Twenty patients with locally advanced prostate cancer were enrolled, and 6 to 12 needle core biopsy specimens were taken from the prostate of each patient before treatment.

Phospho-Akt immunoreactivity in prostate cancer: relationship to disease severity and outcome, Ki67 and phosphorylated EGFR expression.

Background: In the present study, we have investigated the prognostic usefulness of phosphorylated Akt immunoreactivity (pAkt-IR) in prostate cancer using a well-characterised tissue microarray from men who had undergone transurethral resection due to lower urinary tract symptoms.

Methodology/principal Findings: pAkt-IR in prostate epithelial and tumour cells was assessed using a monoclonal anti-pAkt (Ser(473)) antibody. Immunoreactive intensity was determined for 282 (tumour) and 240 (non-malignant tissue) cases.

Nuclear Stat5a/b predicts early recurrence and prostate cancer-specific death in patients treated by radical prostatectomy.

There is an urgent need for reliable markers to identify patients whose prostate cancer (PCa) will recur after initial therapy and progress to lethal disease. Gleason score (GS) is considered the most accurate predictive marker for disease-specific mortality after primary treatment of localized PCa. Most PCas cluster into groups of GS 6 and 7 with considerable variation in the disease recurrence and disease-specific death.

Low endoglin vascular density and Ki67 index in Gleason score 6 tumours may identify prostate cancer patients suitable for surveillance.

Objective: The aim of this study was to explore whether vascular density and tumour cell proliferation are related to the risk of prostate cancer death in patients managed by watchful waiting.

Material And Methods: From a consecutive series of men diagnosed with prostate cancer at transurethral resection in 1975-1990, tissue microarrays (TMAs) were constructed. A majority of men had no metastases at diagnosis and were followed by watchful waiting (n = 295).

Castration therapy of prostate cancer results in downregulation of HIF-1α levels.

Background And Purpose: Neoadjuvant androgen deprivation in combination with radiotherapy of prostate cancer is used to improve radioresponsiveness and local tumor control. Currently, the underlying mechanism is not well understood. Because hypoxia causes resistance to radiotherapy, we wanted to test whether castration affects the degree of hypoxia in prostate cancer.

Prostate cancer increases hyaluronan in surrounding nonmalignant stroma, and this response is associated with tumor growth and an unfavorable outcome.

Our objective was to investigate whether the presence of a tumor increases hyaluronan (HA) levels in surrounding prostate tissues and whether this extratumoral HA influences tumor growth and outcome. From a series of 287 men diagnosed with prostate cancer at transurethral resection and followed up with watchful waiting, tissue microarrays were constructed, stained, and scored for HA. A high HA staining score in the tumor stroma or in nonmalignant prostate tissue stroma were both associated positively with higher Gleason score and larger tumor volume, and was associated with a poor outcome.

LRIG1 and the liar paradox in prostate cancer: a study of the expression and clinical significance of LRIG1 in prostate cancer.

The course of prostate cancer varies greatly, and additional prognostic markers are needed. Leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) is an endogenous inhibitor of growth factor signaling and a proposed tumor suppressor. Publicly available gene expression datasets indicate that LRIG1 may be overexpressed in prostate cancer.

Fatty acid amide hydrolase in prostate cancer: association with disease severity and outcome, CB1 receptor expression and regulation by IL-4.

Background: Recent data have indicated that there may be a dysregulation of endocannabinoid metabolism in cancer. Here we have investigated the expression of the endocannabinoid metabolising enzyme fatty acid amide hydrolase (FAAH) in a well characterised tissue microarray from patients diagnosed with prostate cancer at transurethral resection for voiding problems.

Methodology/principal Findings: FAAH immunoreactivity (FAAH-IR) was assessed in formalin-fixed paraffin-embedded non-malignant and tumour cores from 412 patients with prostate cancer.

Mast cells are novel independent prognostic markers in prostate cancer and represent a target for therapy.

Mast cells affect growth in various human tumors, but their role in prostate cancer (PC) is unclear. Here, we identify mast cells as independent prognostic markers in PC using a large cohort of untreated PC patients with a long follow-up. By analyzing mast cells in different tissue compartments, our data indicate that intratumoral and peritumoral mast cells have anti- opposed to protumor properties.

Low levels of phosphorylated epidermal growth factor receptor in nonmalignant and malignant prostate tissue predict favorable outcome in prostate cancer patients.

Purpose: To explore if the expression of phosphorylated epidermal growth factor receptor (pEGFR) in nonmalignant and malignant prostate tissue is a potential prognostic marker for outcome in prostate cancer patients.

Experimental Design: We used formalin-fixed tissues obtained through the transurethral resection of the prostate from 259 patients diagnosed with prostate cancer after the transurethral resection of the prostate, and patients were then followed with watchful waiting. Tissue microarrays of nonmalignant and malignant prostate tissue were stained with an antibody against pEGFR.

Downstaging and survival benefits of neoadjuvant radiotherapy before cystectomy for patients with invasive bladder carcinoma.

Objective: To compare the long-term outcomes of a series of patients treated with neoadjuvant radiotherapy combined with cystectomy against a later series of patients treated with immediate cystectomy.

Material And Methods: A total of 187 consecutive patients, surgically treated with cystectomy due to cT1-3 transitional cell bladder carcinoma with (n=90) or without (n=97) neoadjuvant radiotherapy, was included in a retrospective analysis. The clinical stage at the primary bladder resection and the pathological reports after the cystectomy were re-evaluated and progression-free, disease-specific and overall survival were calculated.

A high cannabinoid CB(1) receptor immunoreactivity is associated with disease severity and outcome in prostate cancer.

In the light of findings indicating that cannabinoids can affect the proliferation of a number of cancer cell types and that cannabinoid receptor expression is higher in prostate cancer cell lines than in non-malignant cells, we investigated whether the level of cannabinoid 1 receptor immunoreactivity (CB(1)IR) in prostate cancer tissues is associated with disease severity and outcome. Formalin-fixed paraffin-embedded non-malignant and tumour tissue samples from patients who were diagnosed with prostate cancer at a transurethral resection for voiding problems were used. CB(1)IR, which was scored in a total of 399 cases, was associated with the epithelial cell membranes, with little staining in the stroma.

A single instillation of epirubicin after transurethral resection of bladder tumors prevents only small recurrences.

Purpose: We studied whether a single instillation of epirubicin after transurethral bladder tumor resection would influence the interval to and size of the first recurrence.

Materials And Methods: A total of 404 patients from 13 hospitals were randomized to 1 instillation of 50 mg epirubicin or placebo within 6 hours after transurethral resection of bladder tumors.

Results: Of 155 evaluable patients in the epirubicin group 79 (51.

Long-term followup of a randomized study of locally advanced prostate cancer treated with combined orchiectomy and external radiotherapy versus radiotherapy alone.

Purpose: In a randomized study we compared the combination of orchiectomy and radiotherapy to radiotherapy alone as treatment for locally advanced prostate cancer. Patients who were treated only with radiotherapy initially underwent castration therapy at clinical progression, providing the opportunity to compare immediate vs deferred endocrine intervention.

Materials And Methods: In this prospective study 91 patients with locally advanced prostate cancer were randomized to receive external beam radiotherapy (46) or combined orchiectomy and radiotherapy (45) after surgical lymph node staging.

Tumor size, vascular density and proliferation as prognostic markers in GS 6 and GS 7 prostate tumors in patients with long follow-up and non-curative treatment.

Objectives: To investigate the prognostic value of potential markers in localized, Gleason score 6 and 7 prostate cancer (PC).

Methods: From a consecutive series of men with PC diagnosed at transurethral resection (1975-1990), specimens from 132 patients without metastases, with Gleason score (GS) 6 (n=80) or 7 (n=52) tumors followed with watchful waiting were examined. The fraction of resected prostate tissue containing cancer, the micro-vessel density (v.