Performance of theUroVysion^®FISHassay for the diagnosis of malignant effusions using two cutoff strategies

Abstract

The cytological examination of cavity fluids has limited sensitivity in the diagnosis of malignancy. Aneuploidy, which is commonly observed in neoplastic cells, could potentially be used as an ancillary diagnostic tool. To evaluate the detection of aneuploid cells in cavitary effusion samples using the fluorescence in situ hybridization (FISH) assay UroVysion ® with some adaptations and two different cutoff strategies. Seventy samples of pleural or peritoneal fluid with positive (n = 40), negative (n = 15), or suspicious (n = 15) oncotic cytology were subjected to FISH assay with the multitarget UroVysion ® kit, which is composed of probes that hybridize to the centromeric region of chromosomes 3, 7, and 17 and to the locus 9p21. FISH performance was evaluated using two different cutoffs: (1) the manufacturer's cutoff (M‐FISH) and 2) a proposed cutoff (P‐FISH). Using M‐FISH, the diagnostic sensitivity was 57.1%, specificity 87.5%, and accuracy 60.0%; with P‐FISH, the sensitivity was 87.3%, specificity 71.4%, and accuracy 85.7%. When combined with cytology, the sensitivity, specificity, and accuracy were 88.0%, 83.3%, and 87.8%, respectively. Malignant cells presented a predominance of chromosomal gains. The UroVysion ® test using the P‐FISH cutoff was effective in demonstrating aneuploid cells in all malignant effusions, confirming the diagnosis of malignancy even in cases with suspicious cytology.

Are we ready to develop a tiered scheme for the effusion cytology? A comprehensive review and analysis of the literature

“…A total of 73 studies were included in estimating the diagnostic accuracy of serous fluid cytology (excluding seven studies which considered “SFM” and “MAL” as a positive cytology result for malignancy). The number of TP, FP, FN, TN, and sensitivity, specificity, and positive and negative predictive values for individual studies is summarized in Table .…”

Large-Scale Longitudinal Comparison of Urine Cytological Classification Systems Reveals Potential Early Adoption of The Paris System Criteria

“…While cystoscopy followed by biopsy with histological examination is the accepted standard for diagnosis, urine cytology is the preferred mode for detection and screening because: it is inexpensive; has a rapid turn-around time; and specimens are relatively easy to obtain. Abnormal cytology findings usually trigger more invasive and expensive assessment methods (e.g., cystoscopy, FISH) 4,5 , though further investigation is important because these assessments determine treatment options, ranging from follow-up urine cytology to chemotherapy or surgery. This sequence is not entirely foolproof since abnormal cytological findings are subject to a high “false positive” rate (i.e., urine specimen is perceived to be abnormal while cystoscopy/biopsy leads to negative finding).…”

UroVysion Fluorescent in Situ Hybridization (U-FISH) Remains the Most Sensitive Method for Pancreatobiliary Stricture Malignancy Detection

“…The most studied and commonly used -albeit rarely -ancillary technique is UroVysion Fluorescent in situ hybridization (U-FISH) [8]. U-FISH employs FISH probes to detect aneuploidy for chromosomes 3, 7, and 17 as well as a probe to detect loss of the 9p21 locus [9]. U-FISH was developed for urothelial cancer but has found use for other cancers and specimens as aneuploidy is a near universal event in solid tumors and >66% show whole chromosome alterations [10].…”