Evaluating Keratin 17 Expression in Urothelial Malignancies

Noninvasive urine tests for the detection of urothelial carcinoma (UC) typically have low sensitivity, especially in the detection of low-grade cancer. The URO17 test based on the Keratin 17 (K17) biomarker has shown high sensitivity and specificity in detecting both low- and high-grade UC, demonstrating promise as an effective and noninvasive test for bladder cancer. A recent study sought to evaluate K17 expression in multiple forms of UC, and the results were shared during the 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium.

A total of 95 different urine specimens were collected from 2020 to 2021, representing 19 different histological categories of urothelial diseases. The samples were prepared onto slides and tested with the URO17 bladder cancer test (KDx Diagnostics Inc.) on a Dako Autostainer Link 48 using the manufacturer’s recommended procedures. The stained samples were evaluated by a cytopathologist and scored using 5 K17-positive urothelial cells as a cutoff.

K17 was positive in 20/20 (100%) of the UC samples and 23/27 (85%) of the noninvasive papilloma and UC samples. K17 was positive in 100% of carcinoma in situ, papillary urothelial carcinoma, sarcoma, small cell carcinoma, papillary urothelial carcinoma, urothelial papilloma, inverted papilloma, renal-pelvis urothelial carcinoma, and urothelial carcinoma with squamous differentiation.

K17 was also expressed in many cystitis, inflammatory myofibroblastic tumors, and papillary urothelial neoplasm of low malignant potential (PUNLMP), but not in prostate carcinoma. In 19/22 cases (86%), K17 was mostly positive in urine samples from patients with a previous history of bladder cancer, but those samples were histologically determined to be benign. The overall sensitivity of K17 in the cancer group was 88.5% (54/61 positive), with K17 expression occurring in both high-grade and low-grade cancers. Of the 7 false-negative samples, 5 were low grade, 1 was high grade, and 1 was from an inflammatory myofibroblastic tumor.

K17 was found to be highly expressed in almost all UC cases, including those with papillary and squamous characteristics, confirming the high sensitivity of K17 in detecting all UC categories. K17 was also observed in benign and premalignant conditions, including cystitis, PUNLMP, and metaplasia.

Further studies are currently in progress to confirm and expand the utility of K17 for detecting bladder cancer.