Is acinic cell carcinoma a variant of secretory carcinoma? A FISH study using ETV6 ‘split apart’ probes J S Reis-Filho, R Natrajan, R Vatcheva, M B K Lambros, C Marchio ´, B Mahler-Arau ´ jo, C Paish, 1 Z Hodi, 1 V Eusebi 2 & I O Ellis 1 Molecular Pathology Laboratory, The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, 1 Molecular Medical Sciences, Department of Histopathology and University of Nottingham, Nottingham City Hospital NHS Trust, Nottingham, UK, and 2 Department of Anatomical Pathology, Ospedalle Belaria, University of Bologna, Bologna, Italy Date of submission 25 September 2007 Accepted for publication 4 December 2007 Reis-Filho J S, Natrajan R, Vatcheva R, Lambros M B K, Marchio ´ C, Mahler-Arau ´ jo B, Paish C, Hodi Z, Eusebi V & Ellis IO (2008) Histopathology 52, 840–846 Is acinic cell carcinoma a variant of secretory carcinoma? A FISH study using ETV6 ‘split apart’ probes Aims: Acinic cell carcinomas (ACCs) and secretory carcinomas (SCs) of the breast are rare, low-grade malignancies that preferentially affect young female patients. Owing to the morphological and immunohis- tochemical similarities between these lesions, they have been proposed to be two morphological variants of the same entity. It has been demonstrated that SCs of the breast consistently harbour the t(12;15)ETV6-NTRK3 translocation. The aim was to determine whether ACCs also harbour ETV6 gene rearrangements and are thus variants of SCs. Methods and results: Using the ETV6 fluorescence in situ hybridization DNA Probe Split Signal (Dako), the presence of ETV6 rearrangements in three SCs and six ACCs was investigated. Cases were considered as harbouring an ETV6 gene rearrangement if >10% of nuclei displayed ‘split apart signals’ (i.e. red and green signals were separated by a distance greater than the size of two hybridization signals). Whereas the three SCs displayed ETV6 split apart signals in >10% of the neoplastic cells, no ACC showed any definite evidence of ETV6 gene rearrangement. Conclusions: Based on the lack of ETV6 rearrangements in ACCs, our results strongly support the concept that SCs and ACCs are distinct entities and should be recorded separately in breast cancer taxonomy schemes. Keywords: acinic cell carcinoma, breast cancer, chromosomal translocation, classification, fluorescence in situ hybridization, molecular pathology Abbreviations: ACC, acinic cell carcinoma; BAC, bacterial artificial chromosome; CCD, charge coupled device; DAPI, 4¢-6-diamidino-2-phenylindole; ER, oestrogen receptor; FISH, fluorescence in situ hybridization; GCDFP, gross cystic disease fluid protein; PBS, phosphate-buffered saline; PR, progesterone receptor; SC, secretory carcinoma; SSC, NaCl and sodium citrate Introduction Acinic cell carcinoma (ACC) was first described in the breast by Roncaroli et al., 1 in 1996, as one of the types of salivary gland-like tumours of the breast. Since the original description, only 11 additional cases have been reported. 2–10 ACC preferentially affects women, with a wide-range distribution of 35–80 years of age. Address for correspondence: Jorge S Reis-Filho, Molecular Pathology Laboratory, The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK. e-mail: jorge.reis-filho@icr.ac.uk Ó 2008 The Authors. Journal compilation Ó 2008 Blackwell Publishing Limited. Histopathology 2008, 52, 840–846. DOI: 10.1111/j.1365-2559.2008.03046.x