techniques combined were scored for the likelihood of tumour in each area and results were compared with whole-mount analysis.• The area under the receiver operating characteristic curve ( A z ) was used to evaluate accuracy for tumour detection. The association between MR accuracy and Gleason score was statistically assessed.
RESULTS• Of the 456 prostate octants analysed, 145 showed cancer on whole-mount analysis, 120 (83%) of them with a diameter assumed to correspond to a volume > 0.2 cm 3 . Gleason score was ≥ 7 in 68 (47%) tumours.• In the PZ, the A z value was significantly higher for T2W + DWI, T2W + DCE and all three techniques combined than for T2W alone ( P < 0.05).• In the TZ, the A z value was higher for T2W + DWI than for T2W alone, but the difference was not significant.• The A z value for T2W + DWI was significantly higher than that for T2W + DCE or for the three sequences combined.• Gleason score was significantly associated with cancer detection in the PZ.
CONCLUSIONS• Adding DWI and DCE to T2W imaging increased MRI performance in cancer detection in the PZ significantly.• However, this multiparametric model failed to improve performance in the TZ.• Gleason score significantly influenced cancer detection in the PZ but not in the TZ.
When performed with computerized magnetic resonance imaging-transrectal ultrasound image registration, targeted biopsy alone improved cancer detection over random biopsies, decreased the detection rate of microfocal cancer and increased the detection rate of cancer with a Gleason score of greater than 6.
BackgroundChromophobe renal cell carcinoma (chRCC) and renal oncocytoma are two distinct but closely related entities with strong morphologic and genetic similarities. While chRCC is a malignant tumor, oncocytoma is usually regarded as a benign entity. The overlapping characteristics are best explained by a common cellular origin, and the biologic differences between chRCC and oncocytoma are therefore of considerable interest in terms of carcinogenesis, diagnosis and clinical management. Previous studies have been relatively limited in terms of examining the differences between oncocytoma and chromophobe RCC.MethodsGene expression profiling using the Affymetrix HGU133Plus2 platform was applied on chRCC (n = 15) and oncocytoma specimens (n = 15). Supervised analysis was applied to identify a discriminatory gene signature, as well as differentially expressed genes. High throughput single-nucleotide polymorphism (SNP) genotyping was performed on independent samples (n = 14) using Affymetrix GeneChip Mapping 100 K arrays to assess correlation between expression and gene copy number. Immunohistochemical validation was performed in an independent set of tumors.ResultsA novel 14 probe-set signature was developed to classify the tumors internally with 93% accuracy, and this was successfully validated on an external data-set with 94% accuracy. Pathway analysis highlighted clinically relevant dysregulated pathways of c-erbB2 and mammalian target of rapamycin (mTOR) signaling in chRCC, but no significant differences in p-AKT or extracellular HER2 expression was identified on immunohistochemistry. Loss of chromosome 1p, reflected in both cytogenetic and expression analysis, is common to both entities, implying this may be an early event in histogenesis. Multiple regional areas of cytogenetic alterations and corresponding expression biases differentiating the two entities were identified. Parafibromin, aquaporin 6, and synaptogyrin 3 were novel immunohistochemical markers effectively discriminating the two pathologic entities.ConclusionsGene expression profiles, high-throughput SNP genotyping, and pathway analysis effectively distinguish chRCC from oncocytoma. We have generated a novel transcript predictor that is able to discriminate between the two entities accurately, and which has been validated both in an internal and an independent data-set, implying generalizability. A cytogenetic alteration, loss of chromosome 1p, common to renal oncocytoma and chRCC has been identified, providing the opportunities for identifying novel tumor suppressor genes and we have identified a series of immunohistochemical markers that are clinically useful in discriminating chRCC and oncocytoma.
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