Value of magnetic resonance imaging/ultrasound fusion prostate biopsy to select patients for focal therapy.

PURPOSE: To investigate the role of transrectal MRI fusion biopsy to select patients for prostate cancer focal therapy. METHODS: Patients with suspected prostate cancer underwent transrectal MRI fusion biopsy with the Koelis trinity device. Two focal therapy eligibility criteria were subsequently defined: Group 1: PSA ≤ 15 ng/ml, unilateral csPCa, ISUP grade ≤ 2, no contralateral PIRADS 3-5 lesion; Group 2: same criteria but ISUP grade 3. These subgroups were correlated with histopathological post-prostatectomy parameters for stage pT2, unilateral csPCa, no ISUP upgrading. In addition, parameters of csPCa detection were analyzed for patients undergoing primary and re-biopsy. RESULTS: Four hundred fourteen consecutive patients were analyzed (314 for primary biopsy, 100 for re-biopsy). Post-prostatectomy whole mount section analysis was available from 155 patients. 39 and 62 of these patients met focal therapy inclusion criteria for group 1 and group 2, respectively. A correlation with final pathology parameters following radical prostatectomy (stage pT2, unilateral csPCa, no ISUP upgrading) revealed a positive predictive value of only 53.8% and 64.5% for Group 1 and 2, respectively. The overall csPCa detection rate was 73.7%. In the re-biopsy group 20% additional patients with csPCa were detected by targeted biopsy. CONCLUSION: Despite high csPCa detection rates following MRI fusion biopsy our study demonstrated that, using final pathology to confirm locally advanced tumor stage, presence of bilateral csPCa and ISUP upgrading, between 35.5 and 46.2% of patients would have been incorrectly selected for focal therapy.

The potential of comparative genomic hybridization as a tool in the differential diagnosis of matrix-producing bone lesions.

Matrix-producing bone lesions consist of a wide variety of benign and malignant conditions. With respect to morphology, an overlap exists between benign and malignant bone tumors that causes difficulties in the final determination of the tumor. This study was conducted to show the potential of comparative genomic hybridization as a tool in the differential diagnosis of matrix-producing bone lesions. Thirty benign bone tumors were evaluated by conventional comparative genomic hybridization. To test its diagnostic reliability, 5 additional cases were analyzed, all with differential diagnostic difficulties related to morphology and radiology. All were ultimately diagnosed as malignant sarcomas, and unbalanced alterations were detected. In contrast benign tumors or tumor-like lesions did not reveal any chromosomal alterations. Comparative genomic hybridization is a useful adjunct in the complicated differential diagnostic algorithms of matrix-producing bone tumors.

Unequivocal delineation of clinicogenetic subgroups and development of a new model for improved outcome prediction in neuroblastoma.

PURPOSE: Neuroblastoma is a genetically heterogeneous pediatric tumor with a remarkably variable clinical behavior ranging from widely disseminated disease to spontaneous regression. In this study, we aimed for comprehensive genetic subgroup discovery and assessment of independent prognostic markers based on genome-wide aberrations detected by comparative genomic hybridization (CGH). MATERIALS AND METHODS: Published CGH data from 231 primary untreated neuroblastomas were converted to a digitized format suitable for global data mining, subgroup discovery, and multivariate survival analyses. RESULTS: In contrast to previous reports, which included only a few genetic parameters, we present here for the first time a strategy that allows unbiased evaluation of all genetic imbalances detected by CGH. The presented approach firmly established the existence of three different clinicogenetic subgroups and indicated that chromosome 17 status and tumor stage were the only independent significant predictors for patient outcome. Important new findings were: (1) a normal chromosome 17 status as a delineator of a subgroup of presumed favorable-stage tumors with highly increased risk; (2) the recognition of a survivor signature conferring 100% 5-year survival for stage 1, 2, and 4S tumors presenting with whole chromosome 17 gain; and (3) the identification of 3p deletion as a hallmark of older age at diagnosis. CONCLUSION: We propose a new regression model for improved patient outcome prediction, incorporating tumor stage, chromosome 17, and amplification/deletion status. These findings may prove highly valuable with respect to more reliable risk assessment, evaluation of clinical results, and optimization of current treatment protocols.

Genetic imbalances revealed by comparative genomic hybridization in osteosarcomas.

Osteosarcomas are the most frequent bone sarcomas. The molecular chromosomal aberrations in osteosarcomas were analyzed by comparative genomic hybridization (CGH). We studied 47 frozen tumors (41 primary samples, 6 relapses) in osteosarcoma patients registered in the Cooperative Osteosarcoma Study (COSS) protocol. Genomic imbalances were detected in 40 of 41 primary tumors and 6 of 6 relapsed tumors. Gains were more frequent than losses (ratio of 1.3:1). The median number of changes was 16 and 12 in primary and relapsed osteosarcomas, respectively. The median number of aberrations in primary high-grade osteosarcomas (17.0) was significantly higher than in low- or intermediate-grade osteosarcoma subtypes (3.0) (p = 0.038). The most frequent gains included 8q, 1p21-p31 and 1q21-q24, and the most frequent losses were 10q, 5q and 13q. High-level gains were observed on 8q23-q24, 17p13 and 1q21-q24. A gain of 19p (p < 0.001) or loss of 9p (p = 0.027) was more frequent in poor responders than in good responders. Univariate analysis revealed that patients with primary metastases (p = 0.002), poor histologic responses (p = 0.005), high-level gains of 19p (p = 0.012) or losses of 13q14 (p = 0.042) had significantly lower event-free survival (EFS), whereas patients with a loss of 5q (p = 0.007) or a loss of 10q21-22 (p = 0.017) had significantly higher EFS than patients without these aberrations. Multivariate analysis demonstrated that primary metastasis, loss of 13q14 and loss of 5q were independent prognostic factors. The findings of our study seem to be useful for evaluating the prognosis of patients and may finally lead to treatment strategies based on genetic background of osteosarcoma.

Patterns of chromosomal aberrations in urinary bladder tumours and adjacent urothelium.

Bladder cancer is often characterized by recurrent and multifocal growth, and tumours are frequently accompanied by precancerous alterations of the surrounding urothelium. These findings have led to the hypothesis that cells from areas of genetically aberrant but morphologically non-cancerous or even unremarkable mucosa may be the source of bladder carcinomas. Fluorescence in situ hybridization (FISH) was performed using ten probes targeting five different chromosomes that are known to be frequently altered in bladder cancer (centromere 1, 8, 9, 11, 17 and 1p36, 8p23, 9p21, 11q13, 17p13) on paraffin-embedded tissue sections of 11 superficial bladder cancers. Copy number changes of the tumours were compared to those in the urothelium adjacent to the tumour. Eleven of 11 (100%) tumours and eight of 11 (73%) samples of adjacent urothelium showed copy number changes of at least one chromosome. The occurrence of similar patterns of chromosomal aberrations in the tumours and their associated urothelium supports the hypothesis of a clonal relationship. It is concluded that FISH analysis targeting five different chromosomes is more sensitive than conventional histology for distinguishing between neoplastic and normal cells of the urothelium.