Pitfalls in TRAP assay in routine detection of malignancy in effusions

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 po tential use of the telomeric repeat amplification protocol (TRAP) assay as marker for malignancy in cytological effusions. The simple selection criter ion was the cytological diagnosis, and routine samples were classified into malignant (58 samples) and nonmalignant (233 samples). Of the malignant sa mples, 44/58 (76%) were positive by TRAP assay. Of the 14 telomerase-negati ve cytology-positive samples, RNA integrity was poor in 9, indicating subop timal sample conservation for;molecular analysis. In 3 of the remaining 5 s amples with a negative TRAP assay, a high number of malignant cells was obs erved, and these cells might have been telomerase-negative. Thus, the sensi tivity of TRAP assay for the presence of malignant cells was about 76%. In the cytologically nonmalignant effusions, the presence of telomerase activi ty was observed in 24% (55/233). Of these, 6% were highly suspicious for ma lignancy, 9% were doubtful, and 9% were cytologically nonmalignant effusion s confirmed by a follow-up of 12 mo or more. According to these data, the s pecificity of the TRAP assay to detect tumor cells in effusions ranged ly b etween 82-91%. Our results indicate that, although the P assay is positive in 6-15% of putative malignant effusions, the relatively high number of TRA P false-negative and false-positive cases renders this test unsuitable for routine diagnostic purposes. .