The clinical significance of a small focus of well-differentiated carcinoma at prostate biopsy.

Objective: To compare a series of 121 sextant needle biopsy sets with their corresponding radical prostatectomy specimens in screened participants in the European Randomized study of Screening for Prostate Cancer (ERSPC), investigating the effect of screening for prostate cancer on disease-specific mortality and quality of life, as the clinical significance of a small focus of well-differentiated prostate cancer on biopsy is unclear.

Patients And Methods: The expected clinical significance of the discovered tumours was estimated using an arbitrary model combining volume, grade, and stage characteristics.

Results: Of 34 patients who had a small focus (< 3 mm on a single biopsy core) of well-differentiated carcinoma on biopsy, only 18 (53%) were found to have minimal carcinoma (a small focus of well-differentiated carcinoma) at radical prostatectomy, while 16 (47%) had moderately advanced or advanced carcinoma at radical prostatectomy.

Potentially advanced malignancies detected by screening for prostate carcinoma after an interval of 4 years.

Background: At the Rotterdam branch of the European Randomized Study of Screening for Prostate Cancer, a cohort of 19,970 men ages 55-75 years is screened at an interval of 4 years. Screening includes systematic sextant needle biopsy for men with elevated prostate-specific antigen (PSA) levels and/or positive findings on digital rectal examination or transrectal ultrasound. Detection during the second screening round of a large number of high-grade (Gleason Grade 4 or 5) malignancies and/or a large number of malignancies in general could be considered the result of a failure to identify these malignancies at an early stage, during prevalence screening.

MIB-1 (KI-67) proliferation index and cyclin-dependent kinase inhibitor p27(Kip1) protein expression in nephroblastoma.

Purpose: A number of studies have indicated that the tumor proliferation marker MIB-1 and cell cycle inhibitor p27(Kip1) expression are of prognostic importance in a variety of cancers. The present study was performed to evaluate the prognostic value of these molecules in Wilms' tumors.

Experimental Design: MIB-1 and p27(Kip1) expressions were investigated by the means of immunohistochemical analysis of 62 Wilms' tumor.

Evaluation of genetic patterns in different tumor areas of intermediate-grade prostatic adenocarcinomas by high-resolution genomic array analysis.

Prostate cancer is known for its highly heterogeneous histological appearance. Data concerning the cytogenetic content of areas with different histology are sparse. We have genetically evaluated 10 prostatic adenocarcinomas with intermediate histopathological grades (Gleason score 7) that showed two distinctive growth patterns with different pathologies, that is, Gleason grades 3 and 4 (G3 and G4).

Handling and pathology reporting of radical prostatectomy specimens.

Proper examination of radical prostatectomy (RP) specimens by the pathologists is critical in accurately determining the prediction of patient outcome. The pathology report should include relevant clinical information as well as provide prognostically useful data derived from the evaluation of the RP specimen.

Interval carcinomas in the European Randomized Study of Screening for Prostate Cancer (ERSPC)-Rotterdam.

Background: The interval cancer rate is an important parameter for determining the sensitivity of a screening procedure and the screening interval. We evaluated the time and mechanism of detection and the stage distribution of interval prostate cancers diagnosed during a 4-year screening interval.

Methods: We determined the rate of interval cancers and the sensitivity of the screening protocol (involving prostate-specific antigen, digital rectal and transrectal ultrasound examinations) in a cohort of 17 226 men (8350 on the screened arm, 8876 on the control arm) enrolled consecutively on the European Randomized Study of Screening for Prostate Cancer-Rotterdam.

Epidermal growth factor receptor regulates normal urothelial regeneration.

Members of the epidermal growth factor (EGF) family and their receptors are involved in many cellular processes, including proliferation, migration, and differentiation. We have previously reported that these growth factors are expressed and have specific regulatory functions in an organ-like culture model of normal human urothelial cells. Here, we used this model to investigate the involvement of EGF receptor (EGFR) in human urothelial regeneration.

Androgen-independent expression of adrenomedullin and peptidylglycine alpha-amidating monooxygenase in human prostatic carcinoma.

Most of the locally advanced and metastatic prostate carcinomas (PCs) treated with antiandrogenic therapy eventually become refractory to this treatment. Locally produced factors may control prostate tumor biology after androgen withdrawal. Adrenomedullin (AM) is expressed in the prostate and could control cell growth in androgen-independent conditions.

Genetic evaluation of localized prostate cancer in a cohort of forty patients: gain of distal 8q discriminates between progressors and nonprogressors.

Over-representation of sequences on chromosome 7 and 8 have been reported to be associated with aggressive behavior of prostate cancer. In this study we have performed a molecular cytogenetic survey by comparative genomic hybridization of a cohort of 40 prostate cancer patients, consisting of 20 progressors and 20 nonprogressors, after radical surgery for localized adenocarcinoma. Progression was defined as a biochemical relapse, ie, an elevation in prostate-specific antigen level in the serum.

Androgen pathway dysregulation in BRCA1-mutated breast tumors.

Background: Using array analysis for screening RNA from BRCA1-mutated and sporadic breast tumors, we observed that AIGF/FGF-8 expression was lost in BRCA1-mutated breast tumors. Since this growth factor is induced by androgens, we studied the androgen receptor (AR) expression in BRCA-mutated tumors and in matched sporadic breast tumors.

Methods: Paraffin embedded breast tumors of carriers of a BRCA1 mutation (n=41, median age of patients at time of surgery was 41 years [range 28-59 years]) or a BRCA2 mutation (n=14, median age 41 years [range 31-85 years]) were analyzed for the presence of ER-alpha, PR, P53 and AR using standard immunohistochemical techniques.

Molecular grading of urothelial cell carcinoma with fibroblast growth factor receptor 3 and MIB-1 is superior to pathologic grade for the prediction of clinical outcome.

Purpose: Fibroblast growth factor receptor 3 (FGFR3) mutations were recently found at a high frequency in well-differentiated urothelial cell carcinoma (UCC). We investigated the relationship between FGFR3 status and three molecular markers (MIB-1, P53, and P27kip1) associated with worse prognosis and determined the reproducibility of pathologic grade and molecular variables.

Patients And Methods: In this multicenter study, we included 286 patients with primary (first diagnosis) UCC.

Guidelines for processing and reporting of prostatic needle biopsies.

The reported detection rate of prostate cancer, lesions suspicious for cancer, and prostatic intraepithelial neoplasia (PIN) in needle biopsies is highly variable. In part, technical factors, including the quality of the biopsies, the tissue processing, and histopathological reporting, may account for these differences. It has been thought that standardisation of tissue processing might reduce the observed variations in detection rate.

Surveillance with microsatellite analysis of urine in bladder cancer patients treated by radiotherapy.

Objectives: The interpretation of cystoscopy and cytology may be troublesome in bladder cancer patients previously treated by radiotherapy. We evaluated polymerase chain reaction (PCR)-based molecular cytology by microsatellite analysis (MA) and routine urine cytology (RUC) and expert urine cytology (EUC) as modes of surveillance for patients previously treated by radiotherapy with curative intent.

Methods: Eighty-one voided urine samples were obtained from 49 patients prior to cystoscopy and subjected to MA, RUC and EUC.

Morphological assessment of radical prostatectomy specimens. A protocol with clinical relevance.

The increase in prostate cancer detection has induced a sharp increase in the number of radical prostatectomies Proper examination of radical prostatectomy (RP) specimens by pathologists is critical in determining the need for adjuvant treatment and prediction of patient outcome. The pathology report should include relevant clinical information as well as provide prognostically useful information derived from the macroscopic examination and microscopic evaluation of the RP specimen

Expression and prognostic relevance of vascular endothelial growth factor (VEGF) and its receptor (FLT-1) in nephroblastoma.

Aims: To investigate the prognostic relevance of vascular endothelial growth factor (VEGF) and its receptor Flt-1 in nephroblastoma and whether tumour microvessel density (MVD) immunoreactivity, determined by the CD31 antigen, is related to the expression of VEGF and Flt-1.

Methods: The expression of VEGF and Flt-1 and MVD were investigated by means of immunohistochemical analysis in 62 Wilms's tumours. Patients were treated preoperatively with chemotherapy and had a mean follow up of 5.

Combined microsatellite and FGFR3 mutation analysis enables a highly sensitive detection of urothelial cell carcinoma in voided urine.

Purpose: Fibroblast growth factor receptor 3 (FGFR3) mutations were reported recently at a high frequency in low-grade urothelial cell carcinoma (UCC). We investigated the feasibility of combining microsatellite analysis (MA) and the FGFR3 status for the detection of UCC in voided urine.

Experimental Design: In a prospective setting, 59 UCC tissues and matched urine samples were obtained, and subjected to MA (23 markers) and FGFR3 mutation analysis (exons 7, 10, and 15).

Ultrasound-guided fine needle aspiration cytology of axillary lymph nodes in breast cancer patients. A preoperative staging procedure.

Currently, axillary lymph node dissection is increasingly being replaced by the sentinel node procedure. This method is time-consuming and the full immunohistochemical evaluation is usually only first known postoperatively. This study was designed to evaluate the accuracy of preoperative ultrasound-guided fine needle aspirations (FNAs) for the detection of non-palpable lymph node metastases in primary breast cancer patients.

Novel fibroblast growth factor receptor 3 (FGFR3) mutations in bladder cancer previously identified in non-lethal skeletal disorders.

Activating mutations in the fibroblast growth factor receptor 3 (FGFR3) gene are responsible for several autosomal dominant craniosynostosis syndromes and chondrodysplasias i.e. hypochondroplasia, achondroplasia, SADDAN and thanatophoric dysplasia--a neonatal lethal dwarfism syndrome.

Non-sentinel lymph node involvement in patients with breast cancer and sentinel node micrometastasis; too early to abandon axillary clearance.

Aims: It has been suggested that patients with T1-2 breast tumours and sentinel node (SLN) micrometastases, defined as foci of tumour cells smaller than 2 mm, may be spared completion axillary lymph node dissection because of the low incidence of further metastatic disease. To gain insight into the extent of non-sentinel lymph node (n-SLN) involvement, SLNs and complementary axillary clearance specimens in patients with SLN micrometastases were examined.

Methods: A set of 32 patients with SLN micrometastases was selected on the basis of pathology reports and review of SLNs.

A BRCA1/2 mutation, high breast density and prominent pushing margins of a tumor independently contribute to a frequent false-negative mammography.

Female BRCA1/2 mutation carriers develop in up to 50% breast cancer (BC) before age 50 years. We investigated whether the specific histologic features of BRCA1/2-associated breast cancer influence imaging. We correlated the mammographic results with the histology of 34 BC in BRCA1/2 mutation carriers and 34 sporadic cancers in patients, matched for age and year of diagnosis.

Frequent FGFR3 mutations in urothelial papilloma.

Activating point mutations in the FGFR3 gene occur frequently in low-grade and low-stage bladder carcinomas, whereas they are rare in high-grade carcinomas. This study investigates the incidence of FGFR3 mutations in 12 urothelial papillomas and 79 pTaG1 tumours which were regraded according to the 1998 WHO/ISUP classification system, resulting in 62 papillary urothelial neoplasms of low malignant potential (PUNs-LMP) and 17 low-grade papillary urothelial carcinomas (LG-PUCs). FGFR3 mutation analysis of 21 ovarian Brenner tumours was also performed.

Functions of epidermal growth factor-like growth factors during human urothelial reepithelialization in vitro and the role of erbB2.

Transitional epithelium of the urinary bladder can be damaged during, for example, catheterization, overstretching due to obstructed voiding, or partial resection. The subsequent repair process can be stimulated by specific proteins such as epidermal growth factor (EGF) and transforming growth factor-alpha (TGFalpha). However, little is known about the role of EGF-like growth factors and their respective receptors in human urothelial repair.

Different PSA assays lead to detection of prostate cancers with identical histological features.

Objective: Because different PSA assays still show a wide inter-assay variation, we wondered what influence these discrepancies could have on the individual tumour characteristics of the cancers that each of these assays detect in a critical low PSA range. We analysed five different PSA assays in a biopsy simulation with PSA cut-offs of 3.0 and 4.