ORIGINAL ARTICLE Miki (Mitotic Kinetics Regulator) Immunoexpression in Normal Liver, Cirrhotic Areas and Hepatocellular Carcinomas: a Preliminary Study with Clinical Relevance Iván Fernández-Vega 1,2,3,4 & Jorge Santos-Juanes 2 & Emma Camacho-Urkaray 1 & Laura Lorente-Gea 1 & Beatriz García 3 & Francisco Borja Gutiérrez-Corres 1 & Luis M. Quirós 3,5 & Isabel Guerra-Merino 1 & José Javier Aguirre 1 Received: 22 February 2017 /Accepted: 5 February 2018 # Arányi Lajos Foundation 2018 Abstract Hepatocellular carcinoma (HCC) is the most common type of primary malignant tumor in the liver. One of the main features of cancer survival is the generalized loss of growth control exhibited by cancer cells, and Miki is a protein related to the immuno- globulin superfamily that plays an important role in mitosis. We aim to study protein expression levels of Miki in non-tumoral liver and 20 HCCs recruited from a Pathology Department. Clinical information was also obtained. A tissue microarray was performed, and immunohistochemical techniques applied to study protein expression levels of Miki. In normal liver, Miki was weakly expressed, showing nuclear staining in the hepatocytes. Cirrhotic areas and HCCs showed a variety of staining patterns. Most HCC samples showed positive expression, with three different staining patterns being discernible: nuclear, cytoplasmic and mixed. Statistical analysis showed a significant association between grade of differentiation, Ki-67 proliferative index, survival rates and staining patterns. This study has revealed the positive expression of Miki in normal liver, cirrhotic areas and HCCs. Three different staining patterns of Miki expression with clinical relevance were noted in HCCs. Keywords Hepatocellular carcinoma . Miki . Immunohistochemistry . Liver . Immunoglobulin superfamily Introduction Hepatocellular carcinoma (HCC) is the most common type of malignant tumor in the liver and it is one of the most common malignancies worldwide [1]. Despite some improvements in diagnosis and treatment in recent years, prognosis of HCC still remains poor [2]. Replicative immortality is one of the hall- marks of cancer cells, meaning that they no longer respond to many of the signals that control cellular growth and death, thus they are able to evade programmed cell death. As a result, cancer cells divide more rapidly than their progenitors and become less dependent on signals from other cells. In the late stages, cancer cells break through normal tissue boundaries and metastasize to new sites in the body [3]. Miki (mitotic kinetics regulator) is a protein related to the immunoglobulin superfamily that plays an essential role in mitosis. It is the product of the LOC253012 gene and contains three domains suggestive of a cell surface protein: an extreme- ly hydrophobic transmembrane domain-like region, a central region with homology to immunoglobulin superfamily cell adhesion molecules, and an N-terminal putative signal peptide [4]. However, Miki does not appear to be related to cell sur- face, but, rather, it has been localized close to centrosomes and spindles during mitosis [4], and in the perinuclear region (Golgi apparatus) during interphase. In addition, in the late G2 phase, coinciding with the fragmentation of the Golgi apparatus, the poly(ADP-ribosylation) of Miki promotes its * Iván Fernández-Vega ivan_fernandez_vega@hotmail.com 1 Department of Pathology, Hospital Universitario de Araba-Txagorritxu, Vitoria-Gasteiz, Spain 2 Department of Pathology, Hospital Universitario Central de Asturias, Oviedo, Spain 3 Instituto Universitario Fernández-Vega, Oviedo, Spain 4 Service of Anatomic Pathology, Hospital Universitario de Araba-Txagorritxu, C/Jose Atxotegui s/n, E-01009 Vitoria-Gasteiz, Alava, Spain 5 Department of Functional Biology, University of Oviedo, Oviedo, Spain Pathology & Oncology Research https://doi.org/10.1007/s12253-018-0387-7