The purpose of this study was to develop a multitarget, multicolor fluorescence in situ hybridization (FISH) assay for the detection of urothelial carcinoma (UC) in urine specimens. Urinary cells obtained from voided urine specimens of 21 patients with UC and 9 normal donors were analyzed with nine different centromere enumeration probes and a single locus-specific indicator probe to determine an optimal set of FISH probes for UC detection. The four probes with the greatest sensitivity for UC detection were then labeled with a unique fluorophore and combined into a single probe set. The probes with the greatest combined sensitivity for UC detection were CEP3, CEP7, CEP17, and the 9p21 (P16) LSI. This probe set was used to evaluate urine specimens acquired from 179 patients for prospective testing (46 with biopsy-proven UC). FISH slides were evaluated by scanning the slide for cells with nuclear features suggestive of malignancy and assessing the FISH signal pattern of these cells for polysomy (ie, gains of two or more different chromosomes). A receiver operator characteristic curve revealed that a cutoff of 5 cells with polysomy as the positive criterion for cancer resulted in an overall sensitivity of 84.2% for patients with biopsy-proven UC and a specificity of 91.8% among patients with genitourinary disorders but no evidence of UC. This study demonstrates that a multitarget, multicolor FISH assay containing centromeric probes to chromosomes 3, 7, and 17 and a locus-specific probe to band 9p21 has high sensitivity and specificity for the detection of UC in voided urine specimens.

The sensitivity of FISH for the detection of urothelial carcinoma is superior to that of cytology, and the specificity of FISH and cytology for urothelial carcinoma are not significantly different. Further prospective studies are required but FISH has the potential to improve significantly the management of urothelial carcinoma.

A comparative study of the iron-clearing properties of subcutaneously administered desferrioxamine B (DFO) with those of orally administered desferrithiocin sodium salt (1), desmethyl desferrithiocin (2), desazadesmethyl desferrithiocin sodium salt (3), desazadesmethyl desferrithiocin pivaloyloxymethyl ester (4), and desazadesmethyl-5,5- dimethyl desferrithiocin (5) in an iron-loaded Cebus monkey model and a non-iron overloaded bile duct-cannulated rat model is presented. All six drugs, which performed well in rodent studies, demonstrated increased efficiency in the Cebus monkey model. When administered to rodents at a daily dosage of 384 mumol/kg over a period of 10 days, drug 1 demonstrated severe renal toxicity. whereas drugs 3, 4, and 5 exhibited severe gastrointestinal (GI) toxicity. Under the same experimental protocol, drug 2 did not show significant toxic side effects. In addition, to further evaluate the iron-clearing properties of analogue 2, a dose-response study was performed in the primates that showed that iron excretion increased in a dose-dependent fashion.

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Amplification of chromosomal regions leads to an increase of DNA copy numbers and expression of oncogenes in many human tumors. The identification of tumor-specific oncogene targets has potential diagnostic and therapeutic implications. To identify distinct spectra of oncogenic alterations in ovarian carcinoma, metaphase comparative genomic hybridization (mCGH), array CGH (aCGH), and ovarian tumor tissue microarrays were used in this study. Twenty-six primary ovarian carcinomas and three ovarian carcinoma cell lines were analyzed by mCGH. Frequent chromosomal overrepresentation was observed on 2q (31%), 3q (38%), 5p (38%), 8q (52%), 11q (21%), 12p (21%), 17q (21%), and 20q (52%). The role of oncogenes residing in gained chromosomal loci was determined by aCGH with 59 genetic loci commonly amplified in human tumors. DNA copy number gains were most frequently observed for PIK3CA on 3q (66%), PAK1 on 11q (59%), KRAS2 on 12p (55%), and STK15 on 20q (55%). The 11q13-q14 amplicon, represented by six oncogenes (CCND1, FGF4, FGF3, EMS1, GARP, and PAK1) revealed preferential gene copy number gains of PAK1, which is located at 11q13.5-q14. Amplification and protein expression status of both PAK1 and CCND1 were further examined by fluorescence in situ hybridization and immunohistochemistry using a tissue microarray consisting of 268 primary ovarian tumors. PAK1 copy number gains were observed in 30% of the ovarian carcinomas and PAK1 protein was expressed in 85% of the tumors. PAK1 gains were associated with high grade (P < 0.05). In contrast, CCND1 gene alterations and protein expression were less frequent (10.6% and 25%, respectively), suggesting that the critical oncogene target of amplicon 11q13-14 lies distal to CCND1. This study demonstrates that aCGH facilitates further characterization of oncogene candidates residing in amplicons defined by mCGH.

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Axillary lymph node status is crucial in the evaluation of prognosis and in treatment planning of breast cancer. High·resolution real·time sonographic scans of the breast and both axillae were performed on 114 patients with breast carcinoma, all of whom had axillary lymph node dissection and histologic assessment. The sensitivity of high-resolution ultrasonography in the detection of axillary nodal metastases was I tis well recognized that axillary nodal status is the primary prognostic factor in breast cancer. Reports in the literature indicate that current preoperative assessment methods are inadequate.t-4 The aim of this study was to determine the detection rate for axillary lymph node metastases in breast cancer using high-resolution ultrasonography. PATIENTS AND METHODSOne hundred and fourteen consecutive women with newly diagnosed breast cancer (40 stage Tl, 66 stage T2, five stage T3, and three stage T4) were prospectively studied by clinical examination, breast ultrasonography, and x-ray mammography. All had 84.1%, with a specificity of 97.1 %, accuracy of 92.1 %, positive predictive value of 94.9%, and negative predictive value 90.7%. Ultrasonography of the axilla provides good information on anatomy and pathology and may have a potential role in the prognostic work-up of patients who are not surgical candidates.

Background The incidence of recurrent nasopharyngeal carcinoma (NPC) after primary radiotherapy is considerable. The result of re‐irradiation to the recurrent tumor is not satisfactory. Methods Thirty‐one patients who received nasopharyngectomy for treatment of their recurrent nasopharyngeal carcinoma (NPC) (rT1 to rT3) at the Prince of Wales Hospital during the period 1986 to 1997 were reviewed retrospectively. Eleven patients had nasopharyngectomy performed by the transoropalatal approach, 9 patients by the maxillary swing approach, and 11 patients by the mandibular approach. Results Most recurrences (29 of 31) were rT1 and rT2 tumors. No hospital mortality occurred. The common complications of nasopharyngectomy were palatal defect (17 of 31), trismus (15 of 31), otitis media with effusion (20 of 31), dysphagia (12 of 31), and nasal regurgitation (8 of 31). Nine surgical specimens had microscopic invasion of the resection margins. The 5‐year actuarial overall survival, actuarial disease‐free survival, and tumor control were 47%, 42%, and 43%, respectively. The administration of postoperative radiotherapy significantly enhanced survival and tumor control after nasopharyngectomy. Conclusions Nasopharyngectomy supplemented by postoperative radiotherapy achieved significant survival and tumor control with acceptable complications in selected recurrent NPC. It appears to be a better salvage treatment than re‐irradiation alone for selected recurrent NPC. © 2000 John Wiley & Sons, Inc. Head Neck 22: 215–222, 2000.