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Periostin Expression in Neoplastic and Non-Neoplastic Diseases of Bone

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Periostin Expression in Neoplastic and Non-Neoplastic Diseases of Bone Brown et al. Clin Sarcoma Res (2018) 8:18 https://doi.org/10.1186/s13569-018-0105-y Clinical Sarcoma Research RESEARCH Open Access Periostin expression in neoplastic and non‑neoplastic diseases of bone and joint Jennifer M. Brown1, Akiro Mantoku2, Afsie Sabokbar1, Udo Oppermann1, A. Bass Hassan1, Akiro Kudo2 and Nick Athanasou1* Abstract Background: Periostin is a matricellular protein that is expressed in bone and joint tissues. To determine the expres- sion of periostin in primary bone tumours and to assess whether it plays a role in tumour progression, we carried out immunohistochemistry and ELISA for periostin in a range of neoplastic and non-neoplastic bone and joint lesions. Methods: 140 formalin-fxed parafn-embedded sections of bone tumours and tumour-like lesions were stained by an indirect immunoperoxidase technique with a polyclonal anti-periostin antibody. Periostin expression was also assessed in rheumatoid arthritis (RA) and non-infammatory osteoarthritis (OA) synovium and synovial fuid immuno- histochemistry and ELISA respectively. Results: Periostin was most strongly expressed in osteoid/woven bone of neoplastic and non-neoplastic bone- forming lesions, including osteoblastoma, osteosarcoma, fbrous dysplasia, osteofbrous dysplasia, fracture callus and myositis ossifcans, and mineralised chondroid matrix/woven bone in chondroblastoma and clear cell chondrosar- coma. Reactive host bone at the edge of growing tumours, particularly in areas of increased vascularity and fbrosis, also stained strongly for periostin. Vascular elements in RA synovium strongly expressed periostin, and synovial fuid levels of periostin were higher in RA than OA. Conclusions: In keeping with its known role in modulating the synthesis of collagen and other extracellular matrix proteins in bone, strong periostin expression was noted in benign and malignant lesions forming an osteoid or oste- oid-like matrix. Periostin was also noted in other bone tumours and was found in areas of reactive bone and increased vascularity at the edge of growing tumours, consistent with its involvement in tissue remodelling and angiogenesis associated with tumour progression. Keywords: Periostin expression, Bone tumours, Tumour progression Background matrix (ECM) proteins [3–6]. Periostin has a multi- Periostin, a secreted extracellular matrix protein that domain structure in which particular domains bind to belongs to the fasciclin family, was originally character- many proteins and enzymes that promote ECM protein ised in osteoblasts and frst termed osteoblast-specifc crosslinking. Periostin is involved in the formation and factor 2 [1, 2]. Periostin is a matricellular protein that maintenance of normal bone and teeth tissues and is does not have a specifc structural role but rather inter- highly expressed in tissue components that are subject acts with cell surface receptors, proteases and other to mechanical stress, such as the periosteum and the molecules that modulate cell adhesion/migration and periodontal ligament. It has also been observed in other the fbrillogenesis of collagen and other extracellular organs and tissues including heart, breast, lung, thyroid, skin, placenta and ovary [3–6]. *Correspondence: [email protected] Periostin is expressed at sites of injury/repair and 1 Nufeld Department of Orthopaedics, Rheumatology infammation [3, 6, 7]. It has been identifed in rheu- and Musculoskeletal and Sciences, Nufeld Orthopaedic Centre, matoid arthritis (RA) and osteoarthritis (OA) joints University of Oxford, Oxford OX3 7HE, UK Full list of author information is available at the end of the article [8, 9] with a recent study identifying periostin as a key © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creat​iveco​mmons​.org/licen​ses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creat​iveco​mmons​.org/ publi​cdoma​in/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Brown et al. Clin Sarcoma Res (2018) 8:18 Page 2 of 8 regulator in RA synoviocyte migration/invasion asso- Table 1 Bone tumours/tumour-like lesions analysed in this ciated with pannus formation [10]. Periostin is also study expressed in a number of cancers where it is thought, by Tissue type Number various mechanisms, to play a role in tumour progression analysed [3, 6, 11, 12]. Periostin has been identifed in a few bone Osteoma 2 tumours, including fbrous dysplasia and osteosarcoma Osteoid osteoma 4 [13–15], but its expression in other bone neoplasms has Osteoblastoma 6 not been fully investigated. Osteosarcoma, conventional 20 In this study we investigated immunophenotypic Osteosarcoma, telangiectatic 2 expression of periostin in a wide range of primary Osteosarcoma, small cell 2 tumours and tumour-like lesions of bone as well as in Osteosarcoma, parosteal 2 bone secondaries and metastatic osteosarcomas. Our Fibrous dysplasia 10 aims were two-fold: frst, to determine whether periostin Osteofbrous dysplasia 2 expression is increased in specifc bone tumour types; Fracture 2 and second, to examine whether periostin plays a role in Myositis ossifcans 2 tumour progression. Enchondroma 3 Chondroblastoma 9 Methods Chondromyxoid fbroma 3 Neoplastic and non‑neoplastic tissue samples analysed Chondrosarcoma, conventional 20 Tissue samples from 140 biopsies or surgical resections Chondrosarcoma, clear cell 5 of bone tumours and tumour-like lesions, were retrieved Giant cell tumour of bone 8 from the fles of the Nufeld Orthopaedic Centre, His- Aneurysmal bone cyst 4 topathology Department, Oxford (Table 1). Criteria for Solitary bone cyst 2 the histological diagnosis of bone and joint lesions inves- Non-ossifying fbroma 3 tigated in this study were those of the 2013 WHO Clas- Undiferentiated pleomorphic sarcoma 3 sifcation of Tumours of Soft Tissue and Bone [16]. Te Ewing sarcoma 6 tissues were fxed in 10% bufered formalin and, where Adamantinoma of long bone 1 necessary, decalcifed in 5% nitric acid or EDTA. In addi- Chordoma 2 tion, formalin-fxed parafn-embedded sections of syno- Plasma cell myeloma 2 vial tissue derived from patients with RA (n = 21) and Lymphoma 2 OA (n = 19) were examined. Samples of normal bone and Langerhans cell histiocytoma 2 joint tissues from amputation specimens of individuals Metastatic breast carcinoma 3 with no history or evidence of joint disease or neoplasia Metastatic melanoma 1 were used as controls. Synovial fuid (SF) was also aspi- rated from the knee joint of nine patients with OA and nine patients with RA. Ethics approval was obtained from the National Research Ethical Committee, and patient (enzyme-linked immunosorbent assay). Te periostin consent was acquired prior to the collection of samples. concentration was assessed using a Human periostin/ OSF-2 ELISA kit (Adiopo bioscience, Santa Clara, CA, Immunohistochemistry for periostin USA). Statistical evaluation was performed using the Immunohistochemical staining for periostin was carried Mann–Whitney U test with p values less than 0.05 con- out by an indirect immunoperoxidase technique (without sidered as statistically signifcant. any antigen retrieval procedure) using a polyclonal rab- bit antiserum against human periostin raised by using Results peptide DNLDSDIRRGLESNVN (representing aminoac- Periostin expression in normal bone and joint tissues ids 143–158 of human periostin) as an immunogen [13, In normal bone there was strong expression of peri- 17]. As in previous studies [17], the antibody dilution was ostin in collagenous fbrous tissue of the periosteum. At 1:250 and sections of normal skin were employed as a points of tendon or ligament insertion into bone, strong positive control. periostin staining was also seen within collagenous tis- sue. Tere was no staining for periostin in normal lamel- Periostin expression in OA and RA synovial fuid lar cortical and cancellous bone, and osteocytes, bone A quantitative measure of the level of periostin in knee lining cells, osteoblasts and osteoclasts did not express joint RA and OA synovial fuid was determined by ELISA periostin. Fatty and hematopoietic marrow was generally Brown et al. Clin Sarcoma Res (2018) 8:18 Page 3 of 8 negative for periostin but, in some specimens, staining the matrix in areas of tumor cell proliferation. Tere was for periostin was noted in small sinusoidal vascular chan- strong staining for periostin in fbrous dysplasia and oste- nels within the marrow. In normal joints, the synovium ofbrous dysplasia, predominantly in the cellular fbrous and hyaline articular cartilage did not stain for periostin. stroma between bone trabeculae (Fig. 1f). Tere was no specifc staining of the chondroid matrix Periostin expression in tumours and tumour‑like lesions or cartilage cells for periostin in enchondroma, osteo- of bone and joint chondroma, or low/high-grade conventional chondro- Strong staining for periostin was seen in the osteoid sarcoma. Te dense fbrous perichondrium covering matrix formed by osteoblastic cells in neoplastic and osteochondromas (which is continuous with the perios- non-neoplastic bone-forming lesions. Periostin stain- teum) stained strongly for periostin (Fig. 2a). At the base ing was noted in the osteoid matrix covering
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