Telomerase activity and in situ telomerase RNA expression in malignant and non-malignant lymph nodes

K. Yashima, M. A. Piatyszek, H. M. Saboorian, A. K. Virmani, D. Brown, J. W. Shay, A. F. Gazdar

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

Aims/background - Telomerase, an enzyme associated with cellular immortality, is expressed by most malignant tumours; but is inactive in normal somatic cells except for male germ cells and proliferating stem cells. Thus, the measurement of telomerase activity in tissue samples may provide useful diagnostic and prognostic information. The aim of this study was to determine whether telomerase expression is useful for the detection of occult-malignant cells in lymph nodes. Methods - Telomerase activity was compared with histological findings in 123 surgically removed lymph nodes submitted for routine or frozen section diagnosis. Telomerase activity was measured using a modified, semi-quantitative PCR-based telomeric repeat amplification protocol (TRAP). The assay was adapted for single 5 μm OCT embedded cryostat sections. In either fresh tissues or cryostat sections, normalised activity was linear when compared with protein concentration. Furthermore, using an in situ hybridisation method, the human telomerase RNA (hTR) component was measured in a subset of negative and positive nodes. Results - Most (96%) of the 97 histologically negative nodes expressed low levels of activity (mean value of positive samples = 3.0 units/μg protein) which may be derived from activated lymphocytes that express telomerase activity. All 26 malignant nodes (17 metastases, nine lymphomas) expressed telomerase (mean value = 17.8 units/μg protein). The rank order levels between the two groups differed significantly (p = 0.0002). In situ results showed clearly, that the hTR was expressed relatively highly in metastatic cancer cells and at lower levels in germinal centres of secondary follicles. Conclusions - Although expression of telomerase by activated lymphocytes may limit its usefulness, measurement of enzyme activity combined with detection of hTR using in situ hybridisation may assist in the histopathological diagnosis of lymph nodes.

Original languageEnglish (US)
Pages (from-to)110-117
Number of pages8
JournalJournal of Clinical Pathology
Volume50
Issue number2
StatePublished - 1997

Fingerprint

Telomerase
Lymph Nodes
In Situ Hybridization
Lymphocytes
Proteins
Germinal Center
telomerase RNA
Frozen Sections
Enzymes
Germ Cells
Lymphoma
Neoplasms
Stem Cells
Neoplasm Metastasis
Polymerase Chain Reaction

Keywords

  • In situ hybridisation
  • Lymph nodes
  • Telomerase

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Telomerase activity and in situ telomerase RNA expression in malignant and non-malignant lymph nodes. / Yashima, K.; Piatyszek, M. A.; Saboorian, H. M.; Virmani, A. K.; Brown, D.; Shay, J. W.; Gazdar, A. F.

In: Journal of Clinical Pathology, Vol. 50, No. 2, 1997, p. 110-117.

Research output: Contribution to journalArticle

Yashima, K, Piatyszek, MA, Saboorian, HM, Virmani, AK, Brown, D, Shay, JW & Gazdar, AF 1997, 'Telomerase activity and in situ telomerase RNA expression in malignant and non-malignant lymph nodes', Journal of Clinical Pathology, vol. 50, no. 2, pp. 110-117.
Yashima, K. ; Piatyszek, M. A. ; Saboorian, H. M. ; Virmani, A. K. ; Brown, D. ; Shay, J. W. ; Gazdar, A. F. / Telomerase activity and in situ telomerase RNA expression in malignant and non-malignant lymph nodes. In: Journal of Clinical Pathology. 1997 ; Vol. 50, No. 2. pp. 110-117.
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AU - Yashima, K.

AU - Piatyszek, M. A.

AU - Saboorian, H. M.

AU - Virmani, A. K.

AU - Brown, D.

AU - Shay, J. W.

AU - Gazdar, A. F.

PY - 1997

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N2 - Aims/background - Telomerase, an enzyme associated with cellular immortality, is expressed by most malignant tumours; but is inactive in normal somatic cells except for male germ cells and proliferating stem cells. Thus, the measurement of telomerase activity in tissue samples may provide useful diagnostic and prognostic information. The aim of this study was to determine whether telomerase expression is useful for the detection of occult-malignant cells in lymph nodes. Methods - Telomerase activity was compared with histological findings in 123 surgically removed lymph nodes submitted for routine or frozen section diagnosis. Telomerase activity was measured using a modified, semi-quantitative PCR-based telomeric repeat amplification protocol (TRAP). The assay was adapted for single 5 μm OCT embedded cryostat sections. In either fresh tissues or cryostat sections, normalised activity was linear when compared with protein concentration. Furthermore, using an in situ hybridisation method, the human telomerase RNA (hTR) component was measured in a subset of negative and positive nodes. Results - Most (96%) of the 97 histologically negative nodes expressed low levels of activity (mean value of positive samples = 3.0 units/μg protein) which may be derived from activated lymphocytes that express telomerase activity. All 26 malignant nodes (17 metastases, nine lymphomas) expressed telomerase (mean value = 17.8 units/μg protein). The rank order levels between the two groups differed significantly (p = 0.0002). In situ results showed clearly, that the hTR was expressed relatively highly in metastatic cancer cells and at lower levels in germinal centres of secondary follicles. Conclusions - Although expression of telomerase by activated lymphocytes may limit its usefulness, measurement of enzyme activity combined with detection of hTR using in situ hybridisation may assist in the histopathological diagnosis of lymph nodes.

AB - Aims/background - Telomerase, an enzyme associated with cellular immortality, is expressed by most malignant tumours; but is inactive in normal somatic cells except for male germ cells and proliferating stem cells. Thus, the measurement of telomerase activity in tissue samples may provide useful diagnostic and prognostic information. The aim of this study was to determine whether telomerase expression is useful for the detection of occult-malignant cells in lymph nodes. Methods - Telomerase activity was compared with histological findings in 123 surgically removed lymph nodes submitted for routine or frozen section diagnosis. Telomerase activity was measured using a modified, semi-quantitative PCR-based telomeric repeat amplification protocol (TRAP). The assay was adapted for single 5 μm OCT embedded cryostat sections. In either fresh tissues or cryostat sections, normalised activity was linear when compared with protein concentration. Furthermore, using an in situ hybridisation method, the human telomerase RNA (hTR) component was measured in a subset of negative and positive nodes. Results - Most (96%) of the 97 histologically negative nodes expressed low levels of activity (mean value of positive samples = 3.0 units/μg protein) which may be derived from activated lymphocytes that express telomerase activity. All 26 malignant nodes (17 metastases, nine lymphomas) expressed telomerase (mean value = 17.8 units/μg protein). The rank order levels between the two groups differed significantly (p = 0.0002). In situ results showed clearly, that the hTR was expressed relatively highly in metastatic cancer cells and at lower levels in germinal centres of secondary follicles. Conclusions - Although expression of telomerase by activated lymphocytes may limit its usefulness, measurement of enzyme activity combined with detection of hTR using in situ hybridisation may assist in the histopathological diagnosis of lymph nodes.

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