Literature Sharing | "Uncertain" UroVysion Fluorescence In Situ Hybridization Results: Clinical Significance of Diagnostic Terms

Introduction In recent years, the incidence of urothelial carcinoma has been increasing year by year, and it is easy to recur.

It is a multi-source malignant tumor originating from the urothelium.
From the point of view of its occurrence location, it includes renal pelvic cancer and ureteral cancer that occur in the upper urinary tract, and bladder cancer and urethral cancer in the lower urinary tract.
It is the most common type of cancer in the urinary system.
Common malignant tumors.

Among them, upper urothelial cancers are rare, accounting for only 5%-10% of urothelial cancers in clinical practice.

Urine cytology and cystoscopy/ureteroscopy are common methods for diagnosing urothelial cancer.

Genetic studies have shown that urothelial carcinoma is prone to abnormal chromosome number and chromosome aberrations.

Among them, the polysomy of chromosomes 3, 7 and 17 and the deletion of the 9p21 gene are significantly related to the occurrence and recurrence of urothelial carcinoma.

Fluorescence in situ hybridization (FISH) is a common method for detecting genetic abnormalities in urothelial cancer.
The FDA and NMPA have approved FISH for clinical detection of abnormalities in urine exfoliated cells.

The Abbott UroVysion Bladder Cancer Kit is approved by the FDA.
It is designed to detect aneuploidy of chromosomes 3, 7, and 17 and deletion of 9p21 in urine samples of hematuria patients suspected of having bladder cancer by FISH, which is in line with current standards.
The diagnostic procedure is combined as an auxiliary diagnostic method for the preliminary diagnosis of bladder cancer in patients with hematuria and the auxiliary diagnosis method for monitoring the recurrence of bladder cancer after surgery.

One of the positive interpretation criteria of UroVysion FISH: count 25 exfoliated urothelial cells with abnormal morphology, and ≥4 cells have two or more chromosomes (3, 7 or 17) in the same cell as multisomal signals.

The UroVysion FISH results of some cases in clinical testing have 1-3 abnormal cells.
How to interpret this result and manage such patients, a study recently published in the "American Journal of Clinical Pathology" gives recommendations.

Abstract Objective There are UroVysion results with 1-3 abnormal cells.
This part of the cases that do not meet the positive threshold can be better classified as "uncertain".

The purpose of this study is to clarify the incidence and clinical significance of these uncertain UroVysion results.

Methods Retrospective analysis of UroVysion FISH results within 4 years.

Obtain the follow-up results of the initial UroVysion case through the pathology report, including urine cytology or bladder biopsy results within 12 months of the initial diagnosis.

Results A considerable proportion (178/1907, 9.
3%) of cases had uncertain UroVysion results.

Overall, the incidence of secondary malignancies in the UroVysion group with uncertain results (14/59, 23.
7%) was higher than that in the normal group (48/319, 15.
0%), but the difference was not statistically significant (P=0.
124).

In patients with no history of urinary tract tumors, the incidence of secondary malignant tumors in the indeterminate group (7/18, 38.
9%) was significantly higher than that in the normal group (16/103, 15.
5%) (P=0.
044).

Conclusion The research results support the need for closer clinical follow-up of patients with no history of urinary tract tumors with uncertain UroVysion FISH results.

It is recommended that these cases be reported as "aneuploidy of undetermined significance.
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 Literature link: https://doi.
org/10.
1093/ajcp/aqaa254.