Evaluation of Sienna Cancer Diagnostics hTERT Antibody on 500 Consecutive Urinary Tract Specimens

Abstract

Objectives: Telomerase activity can be detected in up to 90% of urothelial carcinomas (UC). Telomerase activity can also be detected in urinary tract cytology (UTC) specimens and indicate an increased risk of UC. We evaluated the performance of a commercially available antibody that putatively binds the telomerase reverse transcriptase (hTERT) subunit on 500 UTC specimens. Study Design: Unstained Cytospin^TM preparations were created from residual urine specimens and were stained using the anti-hTERT antibody (SCD-A7). Two algorithms were developed for concatenating the hTERT result and cytologic diagnosis: a “no indeterminates algorithm,” in which a negative cytology and positive hTERT result are considered positive, and a “high-specificity algorithm,” in which a negative cytology and positive hTERT result are considered indeterminate (and thus negative for comparison to the gold standard). Results: The “no indeterminates algorithm” and “high-specificity algorithm” yielded a sensitivity of 60.6 and 52.1%, a specificity of 70.4 and 90.7%, a positive predictive value of 39.1 and 63.8%, and a negative predictive value of 85.0 and 85.8%, respectively. Conclusions: A positive hTERT result may identify a subset of patients with an increased risk of high-grade UC (HGUC) who may otherwise not be closely followed, while a negative hTERT immunocytochemistry result is associated with a reduction in risk for HGUC.

Clinical application of the anti‐human telomerase reverse transcriptase (hTERT) antibody (SCD‐A7) immunocytochemistry in liquid‐based urine cytology: A prospective, single institute study

“…In our study, hTERT nuclear or nonspecific cytoplasmic staining was also identified in benign urothelial cells, such as umbrella cells or parabasal cells, which confused interpretation in as many as 29 cases (29/337, 8.6%). However, the immunoreactivity for hTERT was weaker in benign cells compared with urothelial carcinoma, which is concordant with the findings of previous studies 24,25 . For instance, Xing et al, 25 who performed ICC on ThinPrep slides, recognized hTERT positivity in normal or nonurothelial cells, yet more often a stronger staining pattern in urothelial carcinoma.…”

“…Two previously published studies using the SCD‐A7 antibody on urine cytology also demonstrated increased hTERT expression rates in urothelial carcinoma. Allison et al 24 demonstrated that nine of the 11 HGUC samples showed hTERT positivity, while in another study by Xing et al 25 six of the nine SGHUC and HGUC samples showed strong staining with hTERT. These consistent findings support hTERT ICC utility in detecting malignant urine cytology samples.…”

“…Two previously published studies using the SCD-A7 antibody on urine cytology also demonstrated increased hTERT expression rates in urothelial carcinoma. Allison et al 24 demonstrated that nine of the 11 HGUC samples showed hTERT positivity, while in another study by Xing et al 25 In the initial application of ICC, however, there was a quality issue related to the immunoreactivity of hTERT. We noticed severe background staining in addition to overstaining of epithelial cells, regardless of several staining protocol alterations, including antibody incubation or retrieval time.…”

“…hTERT was exclusively overexpressed in urothelial carcinoma including SHGUC and HGUC samples ( n = 176/181, 97.2%), as opposed to its low expression in NHGUC samples ( n = 2/87, 2.3%). Since an increased activity of hTERT, which is a catalytic component of the human telomerase, is detected in human cancer but not in most normal cells, this enzyme has been considered as a promising tumor marker in various cancers, including urothelial carcinoma 11,24 . We adopted a specific hTERT antibody, SCD‐A7, which is the first FDA‐approved in vitro diagnostic test for assessing hTERT protein expression in urine cytology.…”

Biomarkers for Precision Urothelial Carcinoma Diagnosis: Current Approaches and the Application of Single-Cell Technologies

“…In a retrospective analysis of 101 cell blocks from UC patients, Khalbuss and Goodison reported that hTERT showed a higher diagnostic sensitivity (84.8%) but lower specificity (65.2%) than cytology (~65% and ~95%, respectively) [ 16 ]. Allison et al evaluated the performance of hTERT in 500 urinary tract cytology specimens and reported a sensitivity of 60.6% and specificity of 70.4% [ 17 ]. Overall, hTERT could be used as an adjunct to urine cytology to aid the identification of patients with an increased risk of high-grade UC.…”