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concordance with histology reaching 98%. Besides ER and PR, the other useful biomarker used in breast cancer is HER2. Immunocytochemical detection of HER2 in cytological specimens is, however, not recommended, because no validation of the quantification of this marker in cytology has yet been reported. For HER2 assessment, the only valid technique for cytological material is in-situ hybridization (ISH).14 HER2 may also be evaluated on cell blocks, as alcohol fixation can cause some autofluorescence that may hinder detection of HER2 amplification using FISH.2 It is important to emphasize that none of these technical details impairs the use of cytological samples obtained from FNAC for studying breast cancer biomarkers, and that using standardized procedures is mandatory for achieving robust and reproducible results. We know that, in general, there is significant resistance among clinicians and histopathologists to accepting any cytological results (morphology and ancillary techniques) for use in patient management. Therefore, misleading titles in scientific articles carry the risk of inducing hasty conclusions. FNAC can be a tool of the utmost importance for routine clinical practice, and clinical trials aimed at metastatic disease on breast cancer are crucial at this moment. The assessment of biomarkers in cytological material is becoming ever more important, and pathologists all need to make efforts to standardize the techniques that they use in histopathology and cytopathology.15

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Fernando Schmitt1 Philippe Vielh2,3 1

Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada, 2Department of Pathology, University Health Network, Toronto, ON, Canada, and 3Department of Medical Biology and Pathology, Translational Research Laboratory and Biobank, Gustave Roussy Comprehensive Cancer Centre, Villejuif, France 1. Stalhammar G, Rosin G, Fredriksson I, Bergh J, Hartman J. Low concordance of biomarkers in histopathological and cytological material from breast cancer. Histopathology 2014; 64; 971–980. 2. Niikura N, Odisio BC, Tokuda Y, Symmans FW, Hortobagyi GN, Ueno NT. Latest biopsy approach for suspected metastases in patients with breast cancer. Nat. Rev. Clin. Oncol. 2013; 10; 711–719. 3. Amir E, Miller N, Geddie W et al. Prospective study evaluating the impact of tissue confirmation of metastatic disease in patients with breast cancer. J. Clin. Oncol. 2012; 30; 587– 592. 4. Cardoso F, Harbeck N, Fallowfield L, Kyriakides S, Senkus E, Group EGW. Locally recurrent or metastatic breast cancer: Histopathology, 66, 314–319.

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ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2012; 23(Suppl. 7); vii11–vii19. Schmitt F, Barroca H. Role of ancillary studies in fine-needle aspiration from selected tumors. Cancer Cytopathol. 2012; 120; 145–160. Dowsett M, Nielsen TO, A’Hern R et al. Assessment of Ki67 in breast cancer: recommendations from the International Ki67 in Breast Cancer Working Group. J. Natl Cancer Inst. 2011; 103; 1656–1664. Chang MC, Chia SK, Voduc D et al. Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J. Natl Cancer Inst. 2009; 101; 736–750. Welsh AW, Moeder CB, Kumar S et al. Standardization of estrogen receptor measurement in breast cancer suggests false-negative results are a function of threshold intensity rather than percentage of positive cells. J. Clin. Oncol. 2011; 29; 2978– 2984. Nofech-Mozes S, Vella ET, Dhesy-Thind S et al. Cancer care Ontario guideline recommendations for hormone receptor testing in breast cancer. Clin. Oncol. (R. Coll. Radiol.) 2012; 24; 684–696. Cano G, Milanezi F, Leitao D, Ricardo S, Brito MJ, Schmitt FC. Estimation of hormone receptor status in fine-needle aspirates and paraffin-embedded sections from breast cancer using the novel rabbit monoclonal antibodies SP1 and SP2. Diagn. Cytopathol. 2003; 29; 207–211. Gong Y, Symmans WF, Krishnamurthy S, Patel S, Sneige N. Optimal fixation conditions for immunocytochemical analysis of estrogen receptor in cytologic specimens of breast carcinoma. Cancer 2004; 102; 34–40. Marinsek ZP, Nolde N, Kardum-Skelin I et al. Multinational study of oestrogen and progesterone receptor immunocytochemistry on breast carcinoma fine needle aspirates. Cytopathology 2013; 24; 7–20. Domanski AM, Monsef N, Domanski HA, Grabau D, Ferno M. Comparison of the oestrogen and progesterone receptor status in primary breast carcinomas as evaluated by immunohistochemistry and immunocytochemistry: a consecutive series of 267 patients. Cytopathology 2013; 24; 21–25. Gu M, Ghafari S, Zhao M. Fluorescence in situ hybridization for HER-2/neu amplification of breast carcinoma in archival fine needle aspiration biopsy specimens. Acta Cytol. 2005; 49; 471–476. Vielh P. Towards credible immunocytochemical findings. Cytopathology 2011; 22; 213–214.

Effective maybe, but is it cost-effective? DOI: 10.1111/his.12424 © 2014 John Wiley & Sons Ltd.

Sir: We read with interest the prospective study of Perry-Keene et al.1 in which total submission of all tissue from 109 pelvic lymphadectomy specimens increased lymph node yield and detection of micrometastases of prostate cancer, with metastasis being detected only in an impalpable lymph node in one patient. Although this finding could have altered the

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management of this patient, total submission of such specimens is probably not cost-effective. It would be interesting to know how many additional blocks had to be submitted in this study to detect this single potentially significant micrometastasis, and the additional cost that would have been incurred. Moreover, even total submission of the specimen does not amount to histological examination of the entire specimen, as only a 5-lm-thick section is examined from each 3-mm-thick slice, which amounts to

Effective maybe, but is it cost-effective?

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