A novel urine cytology stain for the detection and monitoring of bladder cancer.

PURPOSE: CellDetect® is a unique platform technology comprising a proprietary plant extract and 3 dyes that enables color discrimination between malignant (red) and benign (green) cells based on specific metabolic alterations exclusive to the former. Preclinical studies and clinical trials demonstrated the applicability of the new technology in many cell culture lines and various cancers. We explored its performance characteristics in bladder cancer. MATERIALS AND METHODS: We performed an open label, 2-step study at tertiary medical centers. The study enrolled patients with newly diagnosed or a history of urothelial carcinoma. Step 1 involved staining archived biopsies. Slides were evaluated by 2 independent pathologists, who determined the concordance of the new staining technology with the hematoxylin and eosin based diagnosis. Step 2 included staining urine specimens with the new method and comparing findings to the patient final diagnosis and the results of standard urine cytology. RESULTS: A total of 58 archived biopsies were collected. The concordance of staining using the new platform technology with the hematoxylin and eosin based diagnosis was 100%. The new method applied to 44 urine smears showed 94% sensitivity and 89% specificity to detect urothelial carcinoma. Compared to standard urine cytology the new technology had overall superior sensitivity (94% vs 46%), particularly for low grade tumors (88% vs 17%, each p <0.005). There was no significant difference in specificity between the 2 staining techniques. CONCLUSIONS: Findings show the capability of CellDetect to accurately identify urothelial carcinoma. This indicates that the technology can be further developed to provide an alternative urine cytology test with diagnostic value that may have significant clinical benefits.

Screening for cervical neoplasia: a community-based trial comparing Pap staining, human papilloma virus testing, and the new bi-functional Celldetect® stain.

Although cytological screening for cervical neoplasia has lowered mortality rates, current screening methods are plagued by sub-optimal sensitivity and/or specificity. The purpose of this study was to compare the performance of the new CellDetect® staining technology as a potential screening tool. This initial, non-blinded study, utilized samples are taken at a community-based clinic. The diagnostic results using CellDetect® were compared with the performance of Pap staining and human papilloma virus (HPV) testing on the same material, as well as the follow-up biopsies. These data were statistically analyzed in terms of sensitivity, specificity, predictive value (N.P.V and P.P.V), and inter-observer agreement. Bi-functional CellDetect® staining revealed morphological details and tinctorial properties that permitted recognition of neoplasia even at low magnification. Performance-wise, CellDetect® demonstrated non-inferiority for all statistical parameters to both Pap and HPV tests. Importantly, superior sensitivity compared with Pap staining was observed, as well as higher specificity than HPV testing with near equivalent sensitivity. We conclude that CellDetect® is a promising approach to early detection of cervical cancer because of its bi-functional capabilities that afford high sensitivity and specificity. The data suggest that this new methodology warrants further and more extensive clinical evaluation.

Novel dual-function CellDetect® staining technology: wedding morphology and tinctorial discrimination to detect cervical neoplasia.

BACKGROUND: A persistent goal of oncologic histochemistry is to microscopically identify neoplasia tinctorially. Consequently, the newly developed CellDetect® staining technology, that appears to exhibit this property, warrants clinical evaluation. The objective of this study was to compare the diagnostic results using CellDetect® to the outcomes of standard microscopic examination based on hematoxylin and eosin (H&E) staining for the recognition of different squamous epithelial phenotypes of the uterine cervix. METHODS: Pairs of adjacent sections were made from 60 cervical biopsy cases that were diagnosed originally as either normal or neoplastic (CIN, SCC). One section of the pair was stained for H&E; the second section, with CellDetect®. Based on the examination of these pairs by two experienced pathologists, we investigated the following issues:(1) diagnostic agreement between the pathologists on each pair; (2) agreement between H&E and CellDetect® for each pair (3) tinctorial characteristics in micro-regions (n = 130) evaluated as either normal, reactive or neoplastic. RESULTS: Qualitatively, CellDetect®-stained preparations displayed cyto-morphological detail comparable to H&E images. Tinctorially, non-neoplastic cells appeared green/blue when stained withCellDetect®, contrasting with cytologically neoplastic foci, where cells of every grade were red/magenta in color. Due to these tinctorial characteristics, even small foci of neoplasia could be readily distinguished that were inconspicuous on H&E at low magnification. In some instances, this prompted re-examination of the H&E and revision of the diagnosis. Quantitatively, we found that despite diagnostic variation between pathologists, in about 3% of the cases, each pathologist made the same diagnosis regardless of whether CellDetect® or H&E was used, i.e. there was 100% self-agreement for each pathologist between stains. Particularly noteworthy was the finding of a 0% false negative rate, coupled with a 10-15% false positive rate. Regarding specificity, the performance in reactive squamous processes was similar to that observed for morphologically normal squamous epithelium. CONCLUSIONS: In this first order assessment of clinical applicability, CellDetect® staining technology was at least comparable to results using H&E, and perhaps surperior. CellDetect® provided a uniquely useful tinctorial clue for the detection of neoplasia, which exhibited an impressive 0% false negative rate. A more extensive, blinded study is needed to confirm these promising findings.

A color discriminating broad range cell staining technology for early detection of cell transformation.

BACKGROUND: Advanced diagnostic tools stand today at the heart of successful cancer treatment. CellDetect(R) is a new histochemical staining technology that enables color discrimination between normal cells and a wide variety of neoplastic tissues. Using this technology, normal cells are colored blue/green, while neoplastic cells color red. This tinctorial difference coincides with clear morphological visualization properties, mainly in tissue samples. Here we show that the CellDetect(R) technology can be deployed to distinguish normal cells from transformed cells and most significantly detect cells in their early pre-cancerous transformed state. MATERIALS AND METHODS: In tissue culture, we studied the ability of the CellDetect(R) technology to color discriminate foci in a number of two stage transformation systems as well as in a well defined cellular model for cervical cancer development, using HPV16 transformed keratinocytes. RESULTS: In all these cellular systems, the CellDetect(R) technology was able to sensitively show that all transformed cells, including pre-cancerous HPV 16 transformed cells, are colored red, whereas normal cells are colored blue/green. The staining technology was able to pick up: (i) early transformation events in the form of small type 1 foci (non-invasive, not piled up small, with parallel alignment of cells), and (ii) early HPV16 transformed cells, even prior to their ability to form colonies in soft agar. The study shows the utility of the CellDetect(R) technology in early detection of transformation events.