Emerin immunohistochemistry reveals diagnostic features of nuclear membrane arrangement in thyroid lesions Sofia Asioli & Gianni Bussolati Department of Biomedical Sciences and Oncology, University of Turin, Turin, Italy Date of submission 30 July 2008 Accepted for publication 19 September 2008 Asioli S & Bussolati G (2009) Histopathology 54, 571–579 Emerin immunohistochemistry reveals diagnostic features of nuclear membrane arrangement in thyroid lesions Aims: Objective appreciation of irregularities of the nuclear shape is a key parameter in the diagnosis of thyroid lesions, since foldings of the nuclear membrane (NM) featuring indentations, grooves and pseudoinclu- sions characterize papillary thyroid carcinomas (PTC). The aim was to focus on the immunohistochemistry of emerin, a protein of the NM whose decoration best demarcates the nuclear shape. Methods and results: Immunohistochemistry of the NM with emerin as well as three-dimensional reconstruc- tion of the images (through deconvolution processing) performed on a series of 54 cases (processed following the tissue array procedure) revealed a uniform arrange- ment of the NM in non-neoplastic lesions (thyroiditis, microfollicular goitre, follicular adenoma) and normal thyroid as well as in follicular carcinoma. In contrast, irregular folding of the membrane and presence of curling and invaginations, eventually leading to the formation of nuclear pseudoinclusions, was observed in PTC cells. Conclusions: Decoration of the NM represents an original approach to identify PTC nuclear shape, highlights new structural features and might be helpful in the differential diagnosis between so-called nuclear pseudoinclusions and artefactual ‘bubbles’. Keywords: emerin, nuclei, shape, thyroid Abbreviations: 3D, three-dimensional; FA, follicular adenoma; FC, follicular carcinoma; H&E, haematoxylin and eosin; HT, Hashimoto’s thyroiditis; NM, nuclear membrane; PBS, phosphate-buffered saline; PDCa, poorly differentiated carcinoma; PTC, papillary thyroid carcinoma Introduction Irregularities in both nuclear shape and size, coupled with changes in chromatin distribution, remain the basic criteria for cytological diagnosis of cancer in general. Indeed, indentations, undulations and folds of the nuclear membrane (NM), as originally reported by ultrastructural observations of cancer cells, 1 mark a difference from the smooth, roundish nuclear shape of the normal cells of corresponding tissues and organs. This is especially true in thyroid cancer, where infold- ings of the NM, variously manifested by indentations, grooves and pseudinclusions, characterize papillary carcinomas. 2–5 The underlying biological mechanism of these nuclear abnormalities has been studied with in vitro models, with the demonstration that induced gene mutations are associated with tumour-specific nuclear changes and appear to mediate the structural changes of the NM and the chromatin organization that are typical of papillary carcinoma. 6,7 In fact, microinjection into thyroid cells of RET ⁄ PTC oncogene, which leads to activation of a thyrosine-kinase, has been shown to induce NM irregularities within hours, without the requirement for postmitotic NM reassembly. 8 However, despite the widespread use of these mor- phological criteria for the daily cytological diagnoses of thyroid lesions on fine-needle aspiration biopsies, it Address for correspondence: S Asioli, Department of Biomedical Sciences and Human Oncology, Molinette Hospital, University of Turin, Via Santena 7, 10126 Turin, Italy. e-mail: sofia.asioli@unito.it Ó 2009 The Authors. Journal compilation Ó 2009 Blackwell Publishing Limited. Histopathology 2009, 54, 571–579. DOI: 10.1111/j.1365-2559.2009.03259.x