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© 1999 American Society for Clinical Oncology
Telomerase Activity in Fine-Needle Aspirates of Breast LesionsSt Bartholomew's Hospital, London, United Kingdom To the Editor: We read with interest the article by Poremba et al1 in which the authors demonstrated that telomerase activity had a potential role in complementing cytopathologic diagnosis. However, it is important to emphasize that such a potential role should be interpreted only in the context of triple assessment using clinical, radiologic, and cytopathologic data. This is because a certain proportion of benign breast lesions, such as fibroadenomas, express low levels of telomerase levels and a significant percentage of infiltrating carcinomas lack telomerase expression.2 Using a polymerase chain reaction–based radioactive telomeric repeat amplification protocol assay, we examined telomerase activity in 76 breast specimens. Telomerase activity was detected in 34 (72%) of 47 infiltrating ductal carcinomas, but no activity was found in adjacent noncancerous breast tissue specimens (n = 21) or benign breast lesions (n = 5). However, telomerase was expressed in two recurrent phylodes tumors3 (one benign and one malignant) and one atypical hyperplasia lesion. In the latter example, where cytology is usually suspicious of malignancy (C4), the detection of telomerase activity in the specimen could lead to an inappropriate definitive cancer operation for a lesion that requires surveillance only. Further improvements in telomerase assays that allow a more accurate quantification of the enzyme activity could in the future enhance the role of telomerase in breast cancer diagnosis. Poremba et al1 did not report the histopathologic characteristics of the tumors they had examined. We have recently observed a statistically significant association between telomerase activity and tumor size, cellular proliferation (as measured by Ki-67 expression), lymphovascular invasion, and nodal metastases45 which suggests a potential role for telomerase in predicting outcome and guiding systemic therapy. The ability of Poremba et al to reliably detect telomerase activity in 92% of fine-needle aspiration from malignant lesions suggests that telomerase can be used as an in vivo chemosensitivity marker for response to therapy in patients with large breast tumors suitable for neoadjuvant systemic therapy. We are currently examining the effect of tamoxifen on telomerase activity by measuring the enzyme expression on core biopsy specimens obtained before and after tamoxifen activity. Finally, telomerase activity in nipple aspirates obtained using a modified breast pump may prove to be a useful diagnostic test complementing mammography in screening premenopausal women at high risk of breast cancer. REFERENCES
1.
Poremba C, Shroyer RK, Frost M, et al: Telomerase is a highly sensitive and specific molecular marker in fine-needle aspirates of breast lesions. J Clin Oncol17:2020-2026, 1999 2. Sugino T, Yoshida K, Bolodeoku J, et al: Telomerase activity in human breast cancer and benign breast lesions: Diagnostic applications in clinical specimens, including fine needle aspirates. Int J Cancer69:301-306, 1996[Medline] 3. Mokbel K, Parris CN, Ghilchik M, et al: Telomerase activity in phyllodes tumours. Eur J Surg Oncol25:352-355, 1999[Medline] 4. Mokbel K, Parris CN, Ghilchik M, et al: The association between telomerase activity, histopathological parameters, and Ki-67 expression in invasive breast cancer. Am J Surg178:69-72, 1999[Medline] 5. Mokbel K, Parris CN, Ghilchil M, et al: Telomerase activity and lymphovascular invasion in human breast cancer. Eur J Surg Oncol (in press)
ResponseGerhard-Domagk-Institute of Pathology, Westfälische Wilhelms-University, Münster, Germany In Reply: Mokbel et al call attention to important points in our recent publication in the July 1999 issue of the Journal of Clinical Oncology.1 We found that telomerase activity (TA) in fine-needle aspirates (FNAs) of breast lesions is a highly sensitive and specific molecular marker of malignancy that may prove helpful as an adjunct to routine diagnostic cytology, especially when cytologic features of the specimen are inconclusive. We agree with Mokbel et al that TA in breast FNAs should only be interpreted in the context of triple assessment drawing on clinical, radiologic, and cytopathologic data. However, many examples have demonstrated that molecular markers can sometimes be a powerful aid in diagnosis.2 When a pathologist is confronted with a differential diagnosis that has important therapeutic consequences, it is reassuring to have confirmation from molecular testing. It is against this background that we define the potential role of TA analysis in complementing cytopathologic diagnosis. In a previous study on TA in human proliferative breast lesions,3 we examined TA in 98 breast specimens, using a modified semiquantitative and nonradioactive telomeric repeat amplification protocol assay. TA was found in 36 (90%) of 40 infiltrating breast carcinomas and 10 (59%) of 17 cases of ductal carcinoma-in-situ, whereas no activity was found in 21 nonmalignant breast tissues, including samples of normal breast, blunt duct adenosis, papilloma, ductal hyperplasia, and atypical ductal hyperplasia. Furthermore, we found TA in nine of 16 fibroadenomas; of the nine, seven displayed low TA levels, one (from a pregnant woman) showed intermediate TA levels, and one (juvenile fibroadenoma) showed a high TA level. In our investigation, TA in fibroadenomas was found to be correlated with an enhanced cell proliferation rate demonstrated by MIB1 immunostaining. Because most fibroadenomas in our studies13 had low-level TA, careful interpretation is particularly important in cases with equivocal cytologic diagnosis and low TA. The role of telomerase as a prognostic marker in breast cancer remains controversial. In our study on breast cancer specimens,3 we did not find any significant association between TA and nodal status or disease outcome. Mokbel et al themselves report differing results in two of their recent studies: In one study, they found an association between TA and nodal metastasis and cell proliferation,4 whereas another study yielded no such correlation.5 However, we agree that TA in breast FNAs may be used as an in vivo chemosensitivity marker for response to therapy in patients with large breast tumors suitable for neoadjuvant systemic therapy, since there is strong evidence that chemotherapy may abolish TA in tumor cells.67 REFERENCES 1. Poremba C, Shroyer KR, Frost M, et al: Telomerase is a highly sensitive and specific molecular marker in fine-needle aspirates of breast lesions. J Clin Oncol17:2020-2026, 1999 2. Jones D, Fletcher CDM: How shall we apply the new biology to diagnostics in surgical pathology? J Pathol187:147-154, 1999[Medline] 3. Poremba C, Böcker W, Willenbring H, et al: Telomerase activity in human proliferative breast lesions. Int J Oncol12:641-648, 1998[Medline] 4. Mokbel K, Parris CN, Ghilchik M, et al: The association between telomerase, histopathological parameters, and Ki-67 expression in breast cancer. Am J Surg178:69-72, 1999 5. Mokbel K, Parris CN, Radbourne R, et al: Telomerase activity and prognosis in breast cancer. Eur J Surg Oncol25:269-272, 1999[Medline]
6.
Poremba C, Willenbring H, Hero B, et al: Telomerase activity distinguishes between neuroblastomas with good and poor prognosis. Ann Oncol10:715-721, 1999 7. Park KH, Rha SY, Kim CH, et al: Telomerase activity and telomere lengths in various cell lines: Changes of telomerase activity can be another method for chemosensitivity evaluation. Int J Oncol13:489-495, 1998[Medline]
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Copyright © 1999 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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