ORIGINAL ARTICLE

Potential of telomerase expression and activity in cervical specimens as a diagnostic tool

S Bravaccini¹, M A Sanchini¹, A Amadori², L Medri³, L Saragoni³, D Calistri¹, F Monti⁴, A Volpi³ and D Amadori³

¹ Istituto Oncologico Romagnolo, Morgagni-Pierantoni Hospital, Via Forlanini 34, 47100 Forlì, Italy
² Department of Obstetrics and Gynaecology, Morgagni-Pierantoni Hospital
³ Division of Oncology and Diagnostics, Morgagni-Pierantoni Hospital
⁴ Department of Oncology, Infermi Hospital, 47900 Rimini, Italy

Correspondence to:
Correspondence to:
Dr S Bravaccini
Division of Oncology and Diagnostics, Morgagni-Pierantoni Hospital, Via Forlanini 34, 47100 Forlì, Italy; s.bravaccini{at}ausl.fo.it

Aims: To evaluate the potential use of the immunohistochemical expression of telomerase and the measurement of its activity as diagnostic tools in the uterine cervix.

Methods: The fluorescent telomeric repeat amplification protocol (TRAP) assay was used to evaluate telomerase activity in a series of 43 cervical scrapings. Twenty five cases were cytologically classified as inflammatory, and/or metaplastic, and/or acanthotic, and 18 cases presented cell alterations compatible with mild, moderate, or severe cervical intraepithelial neoplasia (CIN). Immunohistochemistry was performed on a retrospective series of 86 archival, paraffin wax embedded blocks using a recently developed anti-hTERT (human telomerase reverse transcriptase) monoclonal antibody.

Results: Telomerase activity was expressed as arbitrary enzymatic units (AEU). Median values were 38.0 AEU for inflammatory non-dysplastic cell specimens, 33.5 AEU for CIN I, 41.0 AEU for CIN II, and 28.0 AEU for CIN III. The median percentage of immunoreactive dysplastic cells, as detected by immunohistochemistry, was significantly (p = 0.024) lower in CIN I (45%) than in more severe dysplastic (CIN II 70%, CIN III 80%) lesions. In contrast, no differences were seen in the enzymatic activity detected by the TRAP assay among the different dysplastic lesions.

Conclusions: These data indicate that, using a molecular extra situ method, the telomerase activity of inflammatory and non-dysplastic elements masks the expected differences between mild and severe dysplasia. Conversely, an in situ approach permits the accurate identification of telomerase positive dysplastic cells.

Abbreviations: AEU, arbitrary enzymatic units; CIN, cervical intraepithelial neoplasia; HPV, human papillomavirus; hTERT, human telomerase reverse transcriptase; PBS, phosphate buffered saline; TRAP, telomeric repeat amplification protocol

Keywords: cervical dysplasia; immunohistochemistry; telomerase; telomeric repeat amplification protocol assay

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