Telomerase Enzyme Activity as a Diagnostic Tool to Distinguish Effusions of Malignant and Benign Origin

Abstract

Telomerase enzyme activity is high in populations of cells that are dividing, and is low or undetectable in quiescent cell populations. Activation of telomerase in tissues that normally lack the capacity for self-renewal is strongly correlated with neoplasia. Telomerase activity can be detected in samples containing very small numbers of cells and studies of human patients suggest that measurement of telomerase activity may be useful for the evaluation of samples that can be obtained in a minimally invasive manner. This study compares the presence or absence of telomerase activity with cytologic evaluation of body cavity effusions, to determine if neoplasia is the underlying cause for the effusion in dogs and cats. Detection of telomerase in effusions was no more sensitive than cytologic evaluation for the identification of underlying neoplasia, and was less specific (telomerase assay: sensitivity ϭ 50%, specificity ϭ 83%; cytology: sensitivity ϭ 50%, specificity ϭ 100%). We conclude that although the telomerase assay may constitute a useful adjunctive test for the diagnosis of neoplasia in some dogs and cats with body cavity effusions, the results of this assay are not sufficiently reliable to be used as a sole diagnostic test.Key words: Canine; Feline; Neoplasia; Telomeric repeat amplification protocol. Neoplastic cell populations are characterized by escape from the regulatory mechanisms that normally limit cell division. The presence of telomerase activity is a hallmark of dividing cells, and activity of this enzyme is extremely low or undetectable in most fully differentiated somatic cell populations. In dividing cells, telomerase plays an essential role in maintaining telomeres, the DNA protein complexes on chromosome ends. Using an internal RNA subunit as a template, telomerase adds telomeric DNA repeats onto chromosome ends to replenish the terminal sequences that are incompletely replicated by the conventional DNA replication machinery.1 Activation of telomerase seems to be a common event enabling unregulated division in cells that have undergone neoplastic transformation, and detection of telomerase activity has been shown to be a sensitive marker for neoplasia in many settings.2-5 Telomerase activity has been detected in human tumors arising from a wide variety of tissues and was recently reported to be present in samples obtained from canine tumors. 2,6,7 An extremely sensitive assay for telomerase activity has been developed (telomeric repeat amplification protocol [TRAP]), enabling detection of the enzyme in samples containing only a few cells.2,8 Several reports have described the application of the TRAP assay to the analysis of fineneedle aspirates, body cavity effusions, and urine samples in human patients. The results of these studies demonstrated that telomerase activity can be reliably detected in such samples and that, as in solid tissues, its presence is corre- lated with neoplasia. [9][10][11][12][13][14][15] This raises the possibility that the telomerase assay may enhance our ability to ...

Evaluation of Telomerase in Canine Mammary Tissues by Immunohistochemical Analysis and a Polymerase Chain Reaction-Based Enzyme-Linked Immunosorbent Assay

“…Several studies have described the relationship between enzyme activity and malignancy of the tumor but, at present, interpretation of the results of such studies remains controversial. 39,43 Various studies of human breast cancer focused on the importance of this enzyme as a diagnostic marker for malignant behavior because the enzyme activity was reported to be correlated to tumor malignancy, 36,44,49 high-stage malignant compared with low-stage, 3,23 in those cases with lymphatic or lymph node invasion, or both, in comparison with those without such an involvement. 34,37 The general idea is that telomerase should not be considered an absolute marker of malignancy; this is because its activity has been found in benign tumors as well, even though high-grade malignant tumors are more often detected with higher levels of expression.…”

Urinary Biomarkers: Review

“…Bu yönüyle DD3, prostat kanseri için gelecek vadeden potansiyel bir üriner biyobelirteç olarak değerlendirilmektedir. 67,99,100 Timozin β15 (TB-15); son zamanlarda tanımlanan, protein yapısında bir üriner biyobelirteçtir. TB-15 5 kDa ağırlığında peptidlerden meydana gelen çoklu β timosin ailesinin bir üyesidir.…”

“…67 Prostat spesfik antijen (PSA); prostat kanserinin tarama ve izlenmesinde kullanılan enzim tabiatında önemli bir belirteçtir. 56,96,100 PSA prostata özgü bir belirteçtir, ancak prostat kanserinin teşhisi noktasında yetersiz kaldığı veya yanlış pozitif/negatif sonuçlar verebildiği için PSA taraması sonrasında biyopsi uygulaması da yapılmaktadır. [98][99][100] Bu sebepten dolayı prostat kanserinin teşhisi ve izlenmesinde yararlanılabilecek üriner biyobelirteçler konusunda araştırmalar devam etmektedir.…”

“…56,96,100 PSA prostata özgü bir belirteçtir, ancak prostat kanserinin teşhisi noktasında yetersiz kaldığı veya yanlış pozitif/negatif sonuçlar verebildiği için PSA taraması sonrasında biyopsi uygulaması da yapılmaktadır. [98][99][100] Bu sebepten dolayı prostat kanserinin teşhisi ve izlenmesinde yararlanılabilecek üriner biyobelirteçler konusunda araştırmalar devam etmektedir. 67,[99][100][101] Matriks metalloproteinaz (MMP); MMP'lerin (MMP-2, 72 kDa, Jelatinaz A ve MMP-9, 92 kDa, Jalatinaz B) tümör büyümesi, metastazı ve anjiyogenezisi gibi patolojik süreçlerde de rol aldığı bildirilmektedir.…”

“…[98][99][100] Bu sebepten dolayı prostat kanserinin teşhisi ve izlenmesinde yararlanılabilecek üriner biyobelirteçler konusunda araştırmalar devam etmektedir. 67,[99][100][101] Matriks metalloproteinaz (MMP); MMP'lerin (MMP-2, 72 kDa, Jelatinaz A ve MMP-9, 92 kDa, Jalatinaz B) tümör büyümesi, metastazı ve anjiyogenezisi gibi patolojik süreçlerde de rol aldığı bildirilmektedir. [28][29][30][31][33][34][35] MMP'nin konsantrasyonundaki artışın, akciğer, göğüs, mide, kolon, ağız ve özefagus yassı hücre karsinomu, ovaryum neoplazisi, melanom, kondrosarkom, prostatik karsinom ve nöroblastom gibi zayıf prognozlu insan maligniteleri, metastazları ve büyümeleriyle alakalı olduğu vurgulanmaktadır.…”