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

Abstract

Objectives Urine cytology is the most widely used noninvasive screening tool for urothelial carcinoma diagnosis and surveillance. Although highly specific, urine cytology exhibits suboptimal sensitivity. This study aimed to determine whether hTERT immunocytochemistry (ICC) could be applicable as an ancillary test in routine cytology practice. Methods A total of 561 urinary tract samples were initially screened in this study. All of them were prepared using SurePath liquid‐based cytology (LBC), while additional LBC slides were made and subsequently used for hTERT (SCD‐A7) ICC. Results From the 561 samples screened, 337 were finally analyzed, all having an adequate cellularity and available follow‐up histology. The hTERT ICC‐positive rate was 95.9% (n = 208/217), 96% (n = 24/25), and 100% (n = 4/4) in cytology samples with high‐grade urothelial carcinoma, carcinoma in situ, and low‐grade urothelial carcinoma subsequent histology. Among the 64 atypical cytology cases histologically confirmed as urothelial carcinomas, 92.2% (n = 59/64) were immunoreactive to hTERT, whereas the two histologically benign cases were ICC‐negative. 87/90 (96.7%) of the cytology cases confirmed to be benign in follow‐up were hTERT‐negative. The overall sensitivity and specificity of hTERT ICC were 96.3% and 98.8%, respectively (AUROC = 0.963; 95% CI = 0.960–0.967). Conclusions The hTERT ICC test exhibited consistent and intense staining in malignant urothelial cells, suggesting its value as an ancillary test in liquid‐based urine cytology.

Polyploid Giant Cancer Cells Are Frequently Found in the Urine of Prostate Cancer Patients

“…TERT expression has been shown, in tissue analyses, to be absent in patients with benign prostatic hyperplasia (BPH) but present in patients with prostatic intraepithelial neoplasia and prostate cancer [ 31 ]. Moreover, TERT expression has been used to detect CTC in blood samples [ 32 ], as well as urothelial carcinoma in the urine of patients with bladder cancer [ 33 ]. We observed a strong cytoplasmic expression of TERT in the PGCC found in urine samples.…”

“…We observed a strong cytoplasmic expression of TERT in the PGCC found in urine samples. Cytoplasmic expression of TERT was already observed in non-clear cell and clear cell hepatocellular carcinoma [ 34 , 35 ], cervical cancer [ 36 ], prostate cancer [ 37 ], and urothelial carcinoma [ 33 ], suggesting possible telomere-independent functions of TERT under conditions of environmental stress such as hypoxia and oxidative stress. As a matter of fact, PGCC are thought to be generated in response to stress conditions.…”