Anti-hTERT Antibody (SCD-A7)

Sienna’s new in-vitro diagnostic (IVD) assay for the detection of hTERT (human TElomerase Reverse Transcriptase), a component of the enzyme telomerase, is now available in Australia. The product is CE marked and is listed on the ARTG as an IVD product. This new test is an immunocytochemistry (ICC) assay for use as an adjunct to urine cytology.

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.

hTERT and Telomerase

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.

 

Clinical Use of hTERT Testing

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%.

 
The study concluded that testing urine samples for hTERT using Sienna’s IVD test, is a clinically useful adjunct to urine cytology, and that:
  • The test may assist in the Identification of patients with an increased risk of bladder cancer
  • Sensitivity for the test was significantly higher than cytology alone, especially in the ability to detect LGUC.
  • The test may be most helpful in circumstances where a patient has a low-risk indeterminate urine cytology result, and negative or absent cystoscopy result. 
  • A positive hTERT result may identify patients with an increased risk of bladder cancer who may otherwise not be closely followed, while a negative hTERT result is associated with a reduction in risk for bladder cancer.
  • The test improves the detection of lesions not well detected by urinary tract cytology alone.

 

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).

 

Case Studies

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.

The cytology result was negative for high-grade urothelial carcinoma (NHGUC). hTERT was detected in urothelial cells by ICC. Histological assessment of the biopsy was positive for low-grade urothelial carcinoma (Ta G1).

Cytology: NHGUC (Negative for High-Grade Urothelial Carcinoma)

(Cytology reporting as per The Paris System for Reporting Urinary Cytology)

hTERT ICC: Positive

The cytology result was reported as atypical (AUC). Urothelial cells were negative for hTERT by ICC. A negative clinical diagnosis was made by cystoscopy.

Cytology: AUC (Atypical)

(Cytology reporting as per the The Paris System for Reporting Urinary Cytology)

hTERT ICC: Negative

The cytology result reported atypical cells present. hTERT was detected in the atypical urothelial cells by ICC. Histological assessment of the biopsy was positive for low-grade urothelial carcinoma (Ta G1).

Cytology: AUC (Atypical)

(Cytology reporting as per The Paris System for Reporting Urinary Cytology)

hTERT ICC: Positive


References

  • Shay JW and Bacchetti S (1997) A survey of telomerase activity in human cancer. Eur J Cancer 33(5):787-791.
  • Allison DB, Sharma R, Cowan ML, VandenBussche CJ: Evaluation of sienna cancer diagnostics hTERT antibody on 500 consecutive urinary tract specimens. Acta Cytol 2018, DOI: 10.1159/000489181
  • The Paris System for Reporting Urinary Cytology (2016) Dorothy L. Rosenthal, Eva M. Wojcik, Daniel F.I. Kurtycz (eds) Springer International Publishing Switzerland
 

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