BACKGROUND: ImmunoCyt (uCyt) and UroVysion are ancillary studies that may aid in the detection of urothelial carcinoma in urine specimens. We compared ImmunoCyt and UroVysion to urine cytology in the ability to detect recurrent urothelial carcinoma. METHODS: Single voided urine samples were obtained from 100 patients who had a previous history of bladder cancer. All patients underwent cystoscopy immediately after urine sample collection. Forty‐one cystoscopically suspicious lesions were biopsied. Urine samples were divided and processed blindly and independently in 3 different laboratories for ImmunoCyt, UroVysion, and urine cytology (ThinPrep method). RESULTS: Of the 41 cystoscopically positive cases, most cystoscopy findings showed multiple tumors that were papillary and less than 1 cm. Biopsies showed many low‐grade tumors (54%). Overall sensitivity of cytology for low‐ and high‐grade urothelial cell carcinoma was 15% and 27%, whereas ImmunoCyt was 62% and 91% and UroVysion was 8% and 18%, respectively. Overall specificity of cytology was 97%, whereas ImmunoCyt was 63% and UroVysion was 90%. CONCLUSIONS: ImmunoCyt is more sensitive than either cytology or UroVysion in detecting low‐grade tumors. Both cytology and UroVysion have comparable specificity in cystoscopically negative cases. Whereas ImmunoCyt may improve the cytological detection of recurrent bladder cancer, UroVysion may be used as a confirmatory test for either cytology or ImmunoCyt. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.
Human cancer cytogenetics is the study of chromosomal rearrangements and numerical abnormalities in malignant tissue. Since the 1960s and the discovery of the Philadelphia chromosome, hundreds of common and characteristic chromosomal aberrations have been observed in various neoplasias. Because these cytogenetic aberrations provide diagnostic, prognostic, and treatment-related information for the associated cancers, they are considered biomarkers for disease. Here we describe many of the best-known chromosome rearrangements and variant rearrangements in hematologic disease and solid tumors, indicate the genes and underlying molecular mechanisms known to be involved in development and progression of disease, and describe the newer molecular cytogenetic technologies and how they are currently being used in cancer diagnostics. We also highlight many important pit-falls in obtaining, transporting, and analyzing neoplastic samples which can compromise cytogenetic studies and preclude its use as a diagnostic tool.
1918 The detection of cytogenetic aberrations in plasma cell neoplasms is definitive for risk stratification. However, metaphase chromosome analysis is limited, due to a low proliferative rate in vitro. Interphase florescent in situ hybridization (FISH) dramatically enhances detection. When detected by FISH, high risk aberrations include complex karyotypes, t(4;14), t(14;16), p53 gene deletions, and hypodiploidy; standard risk aberrations include hyperdiploidy and chromosome 13q deletions detected by FISH only; and low risk aberrations include normal karyotypes, t(6;14), and t(11;14). Despite the utility of interphase FISH in predicting patient outcomes, it is often difficult to detect underlying genetic changes in patients with low levels of clonal plasma cells, such as monoclonal gammopathy of undetermined significance (MGUS) and minimal residual disease (MRD). Plasma cell-targeted FISH can be achieved through 1) simultaneous cytoplasmic light chain staining and FISH, 2) sequential morphologic identification and FISH, 3) immunomagnetic bead depletion of non-plasma cells, or 4) immunomagnetic bead enrichment of plasma cells. Immunomagnetic bead enrichment is superior to other methodologies because it efficiently captures a large number of purified plasma cells for downstream analysis. In this study, we use anti-CD138 coated magnetic beads to enrich bone marrow aspirates containing 1.1% ∼ 5.0% monoclonal plasma cells by flow cytometry, to attain purified samples with approximately 90% plasma cells, for subsequent FISH analysis; we call this procedure Intelligent FISH. We present cytogenetic and morphologic findings on our first 257 cases examined with Intelligent FISH. More than 87% (225/257) of enriched cases exhibit cytogenetic aberrations. In contrast, a matched group of cases analyzed with standard FISH exhibit cytogenetic aberrations in only 31.6% (79/250). These results demonstrate that patients with low levels of plasma cells and normal FISH results may be misclassified as lower risk when they should be considered higher risk, due to lack of sensitivity of conventional FISH techniques. Among our enriched cohort, 22% (57/227) exhibit high risk aberrations, 47% (122/257) exhibit standard risk aberrations, and 30% (78/257) have low risk aberrations. We assess morphologic and immunophenotypic features observed within the different risk groups. These studies show that Intelligent FISH is an efficient and highly valuable technique for accurate risk stratification and detection of minimal disease in patients with plasma cell neoplasms. In particular, it can provide prognostic guidance previously unavailable for the clinical management of MGUS patients. In conclusion, plasma cell enrichment followed by FISH should be incorporated into the standard work-up of MGUS and MRD patients to accurately assess risk, follow-up interval, and treatment options. Disclosures: Keen-Kim: Genoptix Medical Laboratory: Employment. Kaplan:Genoptix Medical Laboratory: Employment. Siva:Genoptix Medical Laboratory: Employment. Wolfe:Genoptix Medical Laboratory: Employment. Nooraie:Genoptix Medical Laboratory: Employment. Chan:Genoptix Medical Laboratory: Employment. Mohrmann:Genoptix Medical Laboratory: Employment.
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