Original Article High-level expression of CD109 is frequently detected in lung squamous cell carcinomas Tomoko Sato, 1 Yoshiki Murakumo, 1 Sumitaka Hagiwara, 1,2 Mayumi Jijiwa, 1 Chikage Suzuki, 1 Yasushi Yatabe 3 and Masahide Takahashi 1,4 Departments of 1 Pathology and 2 Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, 4 Division of Molecular Pathology, Center for Neurological Disease and Cancer, Nagoya University Graduate School of Medicine and 3 Department of Pathology and Molecular Diagnostics, Aichi Cancer Center, Nagoya, Japan CD109 is a glycosylphosphatidylinositol (GPI)-anchored cell surface protein, which is a member of the a2-macroglobulin/ C3, C4, C5 family of thioester-containing proteins. It has been reported that CD109 is expressed in a subset of hematopoietic cells, endothelial cells and several kinds of human tumors. Herein it is reported that the CD109 protein is preferentially expressed in lung squamous cell carcino- mas compared with other types of lung carcinoma including adenocarcinomas, large cell carcinomas and small cell carcinomas. Immunohistochemical staining of surgically resected lung specimens using an anti-CD109 antibody detected CD109 expression in basal cells of bronchial and bronchiolar epithelia and myoepithelial cells of bronchial secretary glands, but not in bronchial and bronchiolar apical epithelial cells and alveolar epithelial cells. Further- more, the CD109 immunoreactivity was observed in squa- mous cell carcinomas at a high frequency compared with other types of lung carcinoma. Although the detailed func- tion of CD109 protein is unclear, these results suggest that CD109 expression may play a role in the development of lung squamous cell carcinoma. Key words: basal cells, CD109, immunohistochemistry, lung cancer, myoepithelial cells, squamous cell carcinoma Tumor development is accompanied by a variety of genetic alterations including point mutations, rearrangements and upregulation or downregulation of gene expression. The identification of proteins the expression of which is specifi- cally altered in tumor tissues is expected to contribute to progress in cancer diagnosis and cancer therapy. CD109 is a glycosylphosphatidylinositol (GPI)-linked glycoprotein on the cell surface, which belongs to the a2-macroglobulin/C3, C4, C5 family. 1–4 It was originally iden- tified as a protein with a molecular mass of approximately 170 kDa using monoclonal antibodies raised against the primitive CD34 + acute myeloid leukemia cell line, KG1a. 1 A series of studies showed that it is expressed on activated T lymphoblasts, activated platelets, endothelial cells, and a subpopulation of CD34 + hematopoietic stem and progenitor cells. 1,2,5 Furthermore, it has been shown that the Gov a/b alloantigen epitopes, which are implicated in refractoriness to platelet transfusion, post-transfusion purpura and neonatal alloimmune thrombocytopenia, are localized to the CD109 protein on platelets, and that a Tyr703Ser polymorphism of CD109 defines Gov a/b alloantigen phenotypes. 6–11 However, the physiological function of CD109 is still unclear. We recently identified CD109 as a gene induced by an oncogenic signal raised by the RET receptor tyrosine kinase with multiple endocrine neoplasia (MEN) 2B mutations. 12–15 Northern blot analysis showed that the transcript of CD109 was detected only in testis in normal human and mouse tissues and upregulated in some human tumor cell lines, suggesting that CD109 exhibits a property of cancer-testis antigen. 15 It was also found that upregulation of the CD109 transcript was more frequently observed in squamous cell carcinomas of lung, esophagus and uterus than in other histological types of carcinoma, on quantitative reverse transcriptase–polymerase chain reaction (RT-PCR) using surgically resected specimens. 15,16 These findings suggest the possibility that CD109 plays a role in oncogenic events of squamous cell carcinomas. In the present study we analyzed CD109 expression in normal lung and lung carcinoma tissues using a rabbit polyclonal antibody against the human CD109 protein. This antibody recognized an endogeneous protein of 180 kDa on Western blotting, which became almost undetectable Correspondence: Yoshiki Murakumo, MD, PhD, Department of Pathology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan. Email: murakumo@med.nagoya-u.ac.jp Received 24 May 2007. Accepted for publication 3 July 2007. © 2007 The Authors Journal compilation © 2007 Japanese Society of Pathology Pathology International 2007; 57: 719–724 doi:10.1111/j.1440-1827.2007.02168.x