Cytological Criteria to Predict Basal Phenotype of Breast Carcinomas Rozany Mucha Dufloth, M.D., Ph.D., 1 Jacy Maria Alves, M.S., 1 Diana Martins, B.Sc., 2 Daniella Serafin Couto Vieira, M.D., M.Sc., 1 Hora ´ cio Chikota, M.D., 3 Luiz Carlos Zeferino, M.D., Ph.D., 4 and Fernando Schmitt, M.D., Ph.D., F.I.A.C. 2,5 * Breast carcinoma is a heterogeneous disease. It can be classified into phenotypes based on the expression of certain proteins, with distinct differences in prognosis. The basal phenotype is associ- ated with worse prognosis and it still remains without specific treatment. However, there is currently no international consen- sus on the cytological criteria that could predict this phenotype. The purpose of the study was to evaluate the cytological criteria in fine-needle aspiration biopsy and to identify their association with the basal phenotype of breast carcinoma. Fine-needle aspiration biopsy specimens and tissue sections (mastectomy specimen) from 74 cases of high-grade invasive ductal breast carcinomas were consecutively retrieved from the files of three institutions. Breast carcinomas were studied using the tissue microarray technique, being classified into phenotypes: luminal A, luminal B, HER2 overexpression, and basal. The cytological criteria for all cases were reviewed blindly by two pathologists according to five cytological criteria: cellularity, cell pattern, presence of necrosis, nucleoli, and nuclear atypia. Exact Fisher test was used to test the association between cytological criteria and the phenotypes of breast carcinoma. Necrosis was present in 64.7% of basal breast carcinomas, and 31.1% of nonbasal breast carcinomas, and that result was statistically significant, showing an odds ratio (OR) of 3.80. The basal phenotype, com- pared with the luminal A, showed more necrosis (OR ¼ 6.97), present/prominent nucleoli (OR ¼ 8.18), and cellularity more frequently (OR ¼ 18.03). Necrosis, as well as present/prominent nucleoli and abundant cellularity are criteria more frequently associated to the basal phenotype of breast carcinoma. Diagn. Cytopathol. 2009;37:809–814. ' 2009 Wiley-Liss, Inc. Key Words: breast cancer; fine needle aspiration cytology; basal cell cancer; cytology Since therapeutic planning is frequently made as a preop- erative multidisciplinary triple approach and fine-needle aspiration cytology (FNAC) is an integral part of this, it is important to gather as much prognostic information from the cytological specimen as possible. 1–7 This proce- dure has become widely accepted as a first-line diagnostic procedure for breast lesions and as a reliable diagnostic tool with both high sensitivity and specificity with mini- mum complications. 8–12 Emerging data demonstrate that stratification of tumors by gene-expression profiles divides breast carcinoma into a mixture of at least two main types, according to hormone estrogen receptor (ER) expression. The hormone receptor-negative group has two subtypes: human epithelial receptor 2 (HER2) overex- pressing and basal-like. The hormone receptor-positive group has two subtypes: luminal A and luminal B. 13–15 Basal breast carcinomas represent one of the most intriguing subtypes because there is no efficient therapy against these lesions, which are often associated with poor prognosis. 16–18 Basal breast carcinomas are thought to arise from the basal epithelial layer of the breast duct. This subgroup has morphology characteristics consisting of a high prolif- erate rate, central necrosis, and pushing border. 6,17,19 FNAC offers a suitable alternative to biopsy in a vari- ety of clinical settings, in which it may be useful to obtain material to study diagnostic, prognostic, and pre- dictive markers. The progress of ‘‘specific’’ therapies based on antibody response will certainly obligate the cytologists to actively participate in the decision-making for therapeutic options for patients. 7,20 1 Department of Pathology, Federal University of Santa Catarina, Floriano ´polis, Brasil 2 IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal 3 IMP Medical Laboratory, Floriano ´polis, Brasil 4 Centro de Atenc ¸a ˜o Integral a ` Sau `de de Mulher (CAISM), Faculty of Medical Sciences, State University of Campinas, Campinas, Brasil 5 Medical Faculty of Porto University, Porto, Portugal *Correspondence to: Fernando Schmitt, M.D., Ph.D., Institute of Mo- lecular Pathology and Immunology of the University of Porto (IPA- TIMUP), Rua Dr. Roberto Frias, s/n, 4200-465 Porto, Portugal. E-mail: fschmitt@ipatimup.pt Received 23 January 2009; Accepted 25 March 2009 DOI 10.1002/dc.21102 Published online 8 May 2009 in Wiley InterScience (www.interscience. wiley.com). ' 2009 WILEY-LISS, INC. Diagnostic Cytopathology, Vol 37, No 11 809