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Telomerase Is a Highly Sensitive and Specific Molecular Marker in Fine-Needle Aspirates of Breast Lesions

From the Gerhard-Domagk-Institute of Pathology, Westfälische Wilhelms-University, Muenster, Germany; Department of Pathology, University of Colorado Health Sciences Center, and Department of Cardiac Research, Veterans Affairs Medical Center, Denver, CO; and Department of Pathology and Laboratory Medicine, Presbyterian Medical Center, University of Pennsylvania, Philadelphia, PA.

Address reprint requests to Barbara Dockhorn-Dworniczak, MD, PhD, Gerhard-Domagk-Institute of Pathology, University of Münster, Domagkstr 17, D-48149 Münster, Germany; email dwornib{at}uni-muenster.de

PURPOSE: Telomerase has been detected in a majority of human malignant tumors, making telomerase activity (TA) one key difference between mortal and immortal cells. In this study, we evaluated in blind-trial fashion the association of TA with cytologic and final clinical/pathologic diagnosis in fine-needle aspirates (FNAs) of breast lesions.

MATERIALS AND METHODS: In 172 FNAs, including 80 samples that were cytologically malignant, 18 that were atypical but not diagnostic for malignancy, and 74 that were cytologically benign, TA was determined by a modified nonradioactive telomeric repeat amplification protocol (TRAP) assay. Final diagnosis was made by pathologic examination of follow-up surgical material available for all the cytologically malignant samples, a majority of the cytologically atypical samples, and a portion of the cytologically benign samples.

RESULTS: TA was detected in 85 of 172 samples. Comparison of the cytologic and histologic diagnoseswith TA showed that 80 of 87 samples from patients with breast cancer were telomerase-positive, resulting in a sensitivity of 92%. TA was found in four of five FNAs from carcinomas that were considered cytologically atypical but not diagnostic for malignancy. Eighty of 85 samples from patients with benign breast lesions were telomerase-negative, revealing a specificity of 94%. The five positive cases in this group were all fibroadenomas with low TA. Among the 18 cases with a cytologic diagnosis of atypia, there was a strong positive relationship between TRAP findings and histologic diagnosis.

CONCLUSION: The detection of TA in FNAs of breast lesions is a highly sensitive and specific marker of malignancy and may be used as an adjunct in cases with an equivocal cytologic diagnosis.

This work was supported in part by the German Research Foundation "Deutsche Forschungsgemeinschaft" (DFG, Po 529/4-1).

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