Pitfalls in TRAP assay in routine detection of maligancy in effusions

R Braunschweig, MD, I Guilleret MSc, Y Theates MD, F Delacrétaz MD, FT Bosman MD PhD, A Mihaescu MD and J Benhattar Phd.

Centre Hospitalier Universitaire Vaudois, Lausanne, Vaud Switzerland

AIM : Telomerase has been found to be reactivated in a majority of cancers but is inactive in most somatic cells. Our principal goal was to determine the potential use of the telomeric repeat amplification protocol (TRAP) assay as marker for malignancy in cytological effusions. METHODS : The simple selection criteria was the cytological diagnosis, and routines samples were classified into malignant (58 samples) and non-malignant (233 samples). TRAP assay was determined on the lysate of these cytological materiel. RESULTS : Of the malignant samples, 44/58 (76%) were positive by the TRAP assay. Of the 14 telomerase-negative cytology-positive samples, RNA integrity was poor in 9, indicating sub-optimal sample conservation for molecular analysis. In 3 of the remaining 5 samples with a negative TRAP assay, a high number of malignant cells was observed and these cells might have been telomerase-negative. Thus, the sensitivity of TRAP assay for the presence of malignant cells was about 76%. In the cytologically non malignant effusions, the presence of telomerase activity was observed in 24% (55/233). Of these, 6% were highly suspicious for malignancy, 9% were doubtful, whereas 9% were cytologically non-malignant effusions confirmed by a follow-up of 12 months or more. According to these data, the specificity of the TRAP assay to detect tumor cells in effusions ranged only between 82 to 91%. CONCLUSIONS : Our results indicate that, although the TRAP assay is positive in 6 to 15% of putative malignant effusions but negative for malignancy by cytological examination, the relatively high number of TRAP false-negative and false-positive cases renders this test unsuitable for routine diagnostic purposes.

KEY WORDS: telomerase, cytology, pleural fluid, periteneal fluid.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Diagnostic Markers.