hTERT positive staining in morphologically normal urothelial cells from a patient that was diagnosed as negative for high grade urothelial carcinoma (NHGUC) by cytology; positive for hTERT ICC and confirmed by biopsy to have a low grade urothelial carcinoma.
Atypical urothelial cells from a patient diagnosed as atypical (AUC) by cytology and positive for hTERT and confirmed by cystoscopy as an upper urinary tract low grade carcinoma.
Telomerase is a biomarker that is not expected to be found in normal urothelial cells collected from the bladder. Its detection in these cells provides pathologists (and the referring urologists) with valuable information that may indicate an increased likelihood of cancer being present, including early-stage lesions that could go undetected by urine cytology alone. Sienna has developed an IVD assay for the detection of hTERT in urothelial cells by ICC. The product, called Anti-hTERT Antibody (SCD-A7), is supplied in a 1mL vial and is available through your local Sienna representative.
A study conducted by Johns Hopkins Hospital, on a cohort of 500 urine specimens, concluded that using hTERT ICC as an adjunct to urine cytology
provides useful clinical information to the diagnosing physician about the likelihood of urothelial carcinoma being present or developing.
When comparing the urine test result to the clinical status for urothelial cancer after follow-up (including a mix of low & high-grade
cancers), adding the hTERT result to urine cytology increased the sensitivity to 52%, compared to 31% for urine cytology alone, while
achieving a specificity of 91%.
“When overexpression of hTERT is detected in urothelial cells, our pathologists have the confidence to inform the clinicians of the potential for neoplasia.”
- Mike Matthews, Director of Molecular Diagnostics, Acupath Laboratories, USA
A malignant cell with abnormal morphological appearance including irregular shape and enlarged nucleus relative to the size of the cell. This cell has also stained positive for hTERT (indicated by the brown nucleus) using the AntihTERT Antibody (SCD-A7).
Normal epithelial cells with normal morphological appearance that are negative for hTERT (indicated by the unstained, blue nuclei).
A cell that appears to be normal from a morphological perspective but staining positive for hTERT (indicated by the brown nucleus).
“Adding urothelial hTERT testing to other clinical information can be valuable when determining the most appropriate follow-up for patients. With hTERT positivity, closer follow-up may be warranted even if other tests are negative for bladder cancer, as hTERT may be an early indicator that a low or even a high-grade cancer is present, or that one may be developing. hTERT is not expected in normal, mature urothelial cells, so when detected, some additional investigation or monitoring may be beneficial to ensure nothing gets missed. On the other hand, a negative hTERT result, particularly in combination with other negative tests, can provide added confidence that cancer is less likely to be present. In some cases, there may be no further testing required at that time.”
- Jed C. Kaminetsky MD, Clinical Assistant Professor of Urology, NYU School of Medicine
As part of the IVD validation, several cases were identified that demonstrate the clinical benefit from the additional information provided by the hTERT ICC assay as an adjunct to cytology.
(Cytology reporting as per The Paris System for Reporting Urinary Cytology)
(Cytology reporting as per the The Paris System for Reporting Urinary Cytology)
(Cytology reporting as per The Paris System for Reporting Urinary Cytology)
References