Telomerase enzyme activity and RNA expression during the multistage pathogenesis of breast carcinoma

Kazuo Yashima, Sara Milchgrub, Lauren S. Gollahon, Anirban Maitra, M. H. Saboorian, Jerry W. Shay, Adi F. Gazdar

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Abstract

Telomerase, an RNA-containing enzyme, is associated with cellular immortality and malignancy. We investigated the role of telomerase during the multistage pathogenesis of breast cancer. We used the semiquantitative, PCR- based telomeric repeat amplification protocol assay for enzyme activity (42 specimens from 42 patients) and a radioactive in situ assay for expression of its RNA component (human telomerase RNA; hTR) for the identification of telomerase-positive cells in archival resection samples (n = 67 from 39 patients). Low telomerase activity was detected in 1 (14%) of 7 samples of benign breast disease, in 4 (67%) of 6 fibroadenomas, in 11 (92%) of 12 carcinoma in situ (CIS) lesions, and in 16 (94%) of 17 invasive breast cancers. There was a progressive increase in the mean telomerase levels with progressive increase in severity of histopathological change (P < 0.05). Almost all of 67 resection samples expressed hTR, irrespective of histology. Expression was low to moderate in some samples of normal epithelium and nonproliferative fibrocystic changes. hTR expression was limited to epithelial cells; expression in stromal cells, including those in fibroadenomas, was negative. Increased hTR expression was observed in some foci of apocrine metaplasia and atypical hyperplasia. Increased hTR expression was also observed in all CIS and invasive lesions, although considerable heterogeneity was noted. Focal up-regulation was frequently noted in CIS lesions in the vicinity of invasive tumors. Thus, up-regulation of hTR may be a predictive marker for invasive tumor development.

Original languageEnglish (US)
Pages (from-to)229-234
Number of pages6
JournalClinical Cancer Research
Volume4
Issue number1
StatePublished - Jan 1998

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Telomerase
Carcinoma in Situ
RNA
Breast Neoplasms
Fibroadenoma
Enzymes
Up-Regulation
Breast Diseases
Metaplasia
Enzyme Assays
Tumor Biomarkers
Stromal Cells
Hyperplasia
Neoplasms
Histology
Epithelium
Epithelial Cells
Polymerase Chain Reaction
telomerase RNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Telomerase enzyme activity and RNA expression during the multistage pathogenesis of breast carcinoma. / Yashima, Kazuo; Milchgrub, Sara; Gollahon, Lauren S.; Maitra, Anirban; Saboorian, M. H.; Shay, Jerry W.; Gazdar, Adi F.

In: Clinical Cancer Research, Vol. 4, No. 1, 01.1998, p. 229-234.

Research output: Contribution to journalArticle

Yashima, Kazuo ; Milchgrub, Sara ; Gollahon, Lauren S. ; Maitra, Anirban ; Saboorian, M. H. ; Shay, Jerry W. ; Gazdar, Adi F. / Telomerase enzyme activity and RNA expression during the multistage pathogenesis of breast carcinoma. In: Clinical Cancer Research. 1998 ; Vol. 4, No. 1. pp. 229-234.
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