Publications by authors named "Jun Nishio"

80 Publications

Histopathologic evaluation of bone marrow lesions in early stage subchondral insufficiency fracture of the medial femoral condyle.

Int J Clin Exp Pathol 2021 15;14(7):819-826. Epub 2021 Jul 15.

Department of Orthopaedic Surgery, Faculty of Medicine, Fukuoka University 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.

Subchondral insufficiency fracture (SIF) of the medial femoral condyle has been proposed to be a primary event in so-called 'spontaneous osteonecrosis of the knee'. SIF is also known to be associated with bone marrow lesions (BML), but the detailed histopathology of the BML has not been fully clarified. We thus investigated the pathophysiology of BML based on MRI and histology in the 4 consecutive patients diagnosed with SIF, whose onset was within 4 months. In all cases, BMLs were enhanced on T1 Gd-enhanced MRI. Histologically, BMLs comprised serous exudate, fibrous tissue, and vascular-rich granulation tissue in the marrow space. In addition, a lower signal intensity line was observed within the BML in all cases on T1 MRI. Histologically, this line showed thickened bone trabeculae accompanied by fibrovascular tissue in two cases, while the other two cases showed formation of woven bone trabeculae around the original fractured bone trabeculae indicating the presence of another fracture in the bone marrow space. In summary, BML in SIF was considered to be a secondary phenomenon resulting from a subchondral fracture.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339717PMC
July 2021

Biology and Management of Dedifferentiated Liposarcoma: State of the Art and Perspectives.

J Clin Med 2021 Jul 22;10(15). Epub 2021 Jul 22.

Department of Orthopaedic Surgery, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.

Dedifferentiated liposarcoma (DDL) is defined as the transition from well-differentiated liposarcoma (WDL)/atypical lipomatous tumor (ALT) to non-lipogenic sarcoma, which arises mostly in the retroperitoneum and deep soft tissue of proximal extremities. It is characterized by a supernumerary ring and giant marker chromosomes, both of which contain amplified sequences of 12q13-15 including () and () cell cycle oncogenes. Detection of (and/or ) amplification serves to distinguish DDL from other undifferentiated sarcomas. Recently, - fusion genes have been identified in a subset of DDL. However, the genetic events associated with dedifferentiation of WDL/ALT remain to be clarified. The standard treatment for localized DDL is surgery, with or without radiotherapy. In advanced disease, the standard first-line therapy is an anthracycline-based regimen, with either single-agent anthracycline or anthracycline in combination with the alkylating agent ifosfamide. Unfortunately, this regimen has not necessarily led to a satisfactory clinical outcome. Recent advances in the understanding of the pathogenesis of DDL may allow for the development of more-effective innovative therapeutic strategies. This review provides an overview of the current knowledge on the clinical presentation, pathogenesis, histopathology and treatment of DDL.
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http://dx.doi.org/10.3390/jcm10153230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348700PMC
July 2021

Current Update on the Diagnosis, Management and Pathogenesis of Elastofibroma Dorsi.

Anticancer Res 2021 May;41(5):2211-2215

Department of Orthopaedic Surgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.

Elastofibroma dorsi is an uncommon benign fibroblastic pseudotumor that typically occurs in the subscapular region of middle-aged or older individuals. The pathogenesis is still unclear and a matter of debate. Magnetic resonance imaging can be used as a first-line investigation of the lesion and reveals a lenticular soft-tissue mass with a signal intensity similar to that of skeletal muscle interlaced with strands of fat. Biopsy is not necessary if all pathognomonic criteria are present. A conservative "wait and see" attitude is reasonable and immediate surgery is no more the standard treatment of elastofibroma dorsi. This review provides an updated overview of the diagnosis, management and pathogenesis of elastofibroma dorsi. We also discuss recent advances in our understanding of genomic alterations in elastofibroma dorsi.
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http://dx.doi.org/10.21873/anticanres.14997DOI Listing
May 2021

Ubiquitin-specific Peptidase 6 ()-associated Fibroblastic/Myofibroblastic Tumors: Evolving Concepts.

Cancer Genomics Proteomics 2021 Mar-Apr;18(2):93-101

Department of Orthopaedic Surgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.

Ubiquitin-specific peptidase 6 (USP6) is a hominoid-specific gene residing on chromosome 17p13 and serves as a deubiquitinating enzyme with a diverse set of functions including intracellular trafficking, inflammatory signaling, cell transformation and protein turnover. USP6 rearrangements were first identified in aneurysmal bone cysts, resulting in promoter swapping and over-expression of wild type USP6. Several morphologically overlapping fibroblastic/myofibroblastic tumors are known to harbor USP6 rearrangements, including nodular fasciitis, cellular fibroma of tendon sheath, myositis ossificans and fibro-osseous pseudotumor of digits. Over the past few years, fusions involving the USP6 gene and various partner genes have been described in these neoplasms. The current World Health Organization Classification of Tumors of Soft Tissue suggests that USP6-rearranged lesions are typically benign and usually self-limited in their growth. This review provides an updated overview of the clinical, histological and molecular genetic features of USP6-associated fibroblastic/myofibroblastic tumors and discusses how these lesions should be best classified.
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http://dx.doi.org/10.21873/cgp.20244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943209PMC
September 2021

An Update on Clinicopathological, Imaging and Genetic Features of Desmoplastic Fibroblastoma (Collagenous Fibroma).

In Vivo 2021 Jan-Feb;35(1):69-73

Department of Orthopaedic Surgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.

Desmoplastic fibroblastoma (also known as collagenous fibroma) is an uncommon benign fibroblastic/myofibroblastic neoplasm that primarily arises in the subcutaneous tissue of upper extremity. Magnetic resonance imaging reveals a well-defined mass in intimate association with dense connective tissue and prominent low signal intensity on all pulse sequences. Peripheral and septal enhancement is usually seen after intravenous contrast. Histologically, the lesion is paucicellular and consists of spindle to stellate-shaped cells embedded in a collagenous or myxocollagenous stroma with low vascularity. Diffuse and strong nuclear immunoreactivity for FOS-like antigen 1 seems to be characteristic of desmoplastic fibroblastoma. Cytogenetic studies have demonstrated the presence of 11q12 rearrangements and an identical t(2;11)(q31;q12) translocation. This review provides an updated overview of the clinical, radiological, histological, cytogenetic and molecular genetic features of desmoplastic fibroblastoma and discusses the relationship to fibroma of tendon sheath.
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http://dx.doi.org/10.21873/invivo.12233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880796PMC
June 2021

Giant Cell Tumor of Tendon Sheath With a t(1;1)(p13;p34) Chromosomal Translocation.

Anticancer Res 2020 Aug;40(8):4373-4377

Department of Orthopaedic Surgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.

Background: Giant cell tumor of tendon sheath (GCTTS) is a benign soft-tissue tumor that occurs predominantly in the fingers, with the capacity for local recurrence. The cytogenetic hallmark of GCTTS is the presence of 1p13 rearrangement. Several chromosomal segments have been recognized as translocation partners to 1p13. Herein, we describe a novel cytogenetic finding of GCTTS arising in the right thumb of a 71-year-old man.

Case Report: Physical examination revealed a 4-cm, elastic hard, immobile, nontender mass. Magnetic resonance imaging demonstrated a nodular mass with reduced signal intensity on both T1- and T2-weighted images. Contrast-enhanced fat-suppressed T1-weighted images showed intense heterogeneous enhancement of the mass. After a needle biopsy, complete excision was performed. Histologically, the tumor was composed of mononuclear cells admixed with multinucleated osteoclast-like giant cells, hemosiderin-laden macrophages, foamy cells, and inflammatory cells. Cytogenetic analysis revealed a reciprocal t(1;1)(p13;p34) translocation as the sole structural aberration.

Conclusion: To the best of our knowledge, this is the first report of this tumor with t(1;1)(p13;p34).
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http://dx.doi.org/10.21873/anticanres.14440DOI Listing
August 2020

Probabilistic modeling of personalized drug combinations from integrated chemical screen and molecular data in sarcoma.

BMC Cancer 2019 Jun 17;19(1):593. Epub 2019 Jun 17.

Children's Cancer Therapy Development Institute, 12655 SW Beaverdam Road-West, Beaverton, OR, 97005, USA.

Background: Cancer patients with advanced disease routinely exhaust available clinical regimens and lack actionable genomic medicine results, leaving a large patient population without effective treatments options when their disease inevitably progresses. To address the unmet clinical need for evidence-based therapy assignment when standard clinical approaches have failed, we have developed a probabilistic computational modeling approach which integrates molecular sequencing data with functional assay data to develop patient-specific combination cancer treatments.

Methods: Tissue taken from a murine model of alveolar rhabdomyosarcoma was used to perform single agent drug screening and DNA/RNA sequencing experiments; results integrated via our computational modeling approach identified a synergistic personalized two-drug combination. Cells derived from the primary murine tumor were allografted into mouse models and used to validate the personalized two-drug combination. Computational modeling of single agent drug screening and RNA sequencing of multiple heterogenous sites from a single patient's epithelioid sarcoma identified a personalized two-drug combination effective across all tumor regions. The heterogeneity-consensus combination was validated in a xenograft model derived from the patient's primary tumor. Cell cultures derived from human and canine undifferentiated pleomorphic sarcoma were assayed by drug screen; computational modeling identified a resistance-abrogating two-drug combination common to both cell cultures. This combination was validated in vitro via a cell regrowth assay.

Results: Our computational modeling approach addresses three major challenges in personalized cancer therapy: synergistic drug combination predictions (validated in vitro and in vivo in a genetically engineered murine cancer model), identification of unifying therapeutic targets to overcome intra-tumor heterogeneity (validated in vivo in a human cancer xenograft), and mitigation of cancer cell resistance and rewiring mechanisms (validated in vitro in a human and canine cancer model).

Conclusions: These proof-of-concept studies support the use of an integrative functional approach to personalized combination therapy prediction for the population of high-risk cancer patients lacking viable clinical options and without actionable DNA sequencing-based therapy.
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http://dx.doi.org/10.1186/s12885-019-5681-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6580486PMC
June 2019

Motor-Evoked Potential Analysis of Femoral Nerve Status During the Direct Anterior Approach for Total Hip Arthroplasty.

J Bone Joint Surg Am 2018 Apr;100(7):572-577

Department of Orthopaedic Surgery, Fukuoka University Faculty of Medicine, Fukuoka, Japan.

Background: During the direct anterior approach for total hip arthroplasty, a retractor is placed on the anterior wall of the acetabulum to retract the iliopsoas muscle. This step with the retractor has been reported to put the patient at risk for femoral nerve damage. The present study aimed to clarify the effects of the anterior acetabular retractor on the status of the femoral nerve during the direct anterior approach on the basis of transcranial motor-evoked potential (MEP) analysis.

Methods: Between July 2016 and February 2017, 22 patients underwent primary total hip arthroplasty via the direct anterior approach with MEP analysis. The integrity of the femoral nerve was tested at 3 time points: preoperatively, as a control (first period); just after retractor placement on the anterior wall of the acetabulum (second period); and after the procedure (third period). The association between operative time and femoral nerve status was examined. Postoperative femoral nerve damage was determined by the presence of causalgia and the results of a manual muscle test (MMT) for strength of knee extension.

Results: The mean amplitude of the femoral nerve was significantly reduced, from 100% in the first period to 54% (range, 5% to 100%) in the second period (p < 0.01), but then significantly improved to 77% (range, 20% to 100%) in the third period (p < 0.01). In 17 (77%) of the 22 patients, the amplitude of the femoral nerve in the second period was reduced, while only 5 patients (23%) showed no reduction. The mean operative time was 83 minutes (range, 63 to 104 minutes), and no significant correlation was observed between operative time and improvement of femoral nerve status between the second and third periods (p = 0.83 and r = -0.05). All 22 patients had a postoperative MMT grade of 5 for knee extension without causalgia of the femoral nerve.

Conclusions: On the basis of the MEP analysis, 17 (77%) of the 22 patients showed a significant reduction of the femoral nerve amplitude despite careful placement of the retractor on the anterior wall of the acetabulum. Although this reduction appears reversible, placement of an anterior retractor should be performed with careful attention to the femoral nerve.

Level Of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
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http://dx.doi.org/10.2106/JBJS.17.00679DOI Listing
April 2018

Incidence of delayed union one year after peri-acetabular osteotomy based on computed tomography.

Int Orthop 2018 05 10;42(5):1029-1034. Epub 2017 Oct 10.

Department of Orthopaedic Surgery, Fukuoka University Faculty of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 810-0180, Japan.

Background: Pubic bone nonunion and delayed union are reported as post-operative complications after peri-acetabular osteotomy (PAO). However, few studies have determined the incidence of delayed union using computed tomography (CT) scans. This study aimed to determine the incidence of delayed union at one year after PAO using X-ray and CT scans.

Methods: We performed a retrospective review of 150 hips in 132 consecutive patients with acetabular dysplasia who underwent PAO between January 2012 and June 2016 and evaluated 107 hips for which pelvic CT scans taken at one year after PAO were available. Clinical evaluations included age at surgery, weight, body mass index (BMI) and history. Radiographic evaluations were to assess pubic, ischial and iliac delayed union at one year post-operatively.

Results: Based on X-ray analysis, the incidence of delayed union in the pubic, ischial and iliac bones was 11.2% (12 hips), 5.6% (6 hips) and 0% (0 hips), respectively, and20.6% (22 hips), 8.4% (9 hips) and 0% (0 hips), respectively, based on CT scans.

Conclusion: The incidence of delayed union of the pubis and ischium at one year after PAO according to CT scans was higher than that based on X-ray imaging. CT scans are useful in patients with some symptoms at the osteotomy site.

Level Of Evidence: Level III.
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http://dx.doi.org/10.1007/s00264-017-3656-2DOI Listing
May 2018

Intra-articular angiofibroma of soft tissue of the knee: A case report.

Mol Clin Oncol 2017 Aug 21;7(2):229-232. Epub 2017 Jun 21.

Department of Orthopaedic Surgery, Faculty of Medicine, Fukuoka University, Fukuoka 814-0180, Japan.

Angiofibroma of soft tissue (AFST) is an extremely rare soft tissue neoplasm that typically presents as a slow-growing, painless mass in the extremities. The present study reports an unusual case of an intra-articular AFST occurring in the left knee of a 23-year-old female. Physical examination revealed a 3-cm, relatively mobile, elastic-hard, non-tender mass. Magnetic resonance imaging detected an intra-articular soft tissue mass with iso-signal intensity relative to skeletal muscle on T1-weighted sequences and heterogeneous high signal intensity on T2-weighted sequences. Contrast-enhanced fat-suppressed T1-weighted sequences demonstrated strong peripheral enhancement of the mass. An arthroscopic excision of the mass was performed. Histologically, the tumor was composed of spindle- or oval-shaped cells in a fibromyxoid stroma with a prominent vascular pattern. Immunohistochemically, the tumor cells were diffusely positive for vimentin and CD163 and focally positive for CD68, desmin and estrogen receptor. Based on these findings, the tumor was diagnosed as an AFST. The patient had no evidence of local recurrence within 9 months of follow-up. To the best of our knowledge, this is the first case of intra-articular AFST managed successfully with arthroscopic excision.
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http://dx.doi.org/10.3892/mco.2017.1298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5532633PMC
August 2017

Chondrolipoma of the Ankle in a Child: A Case Report.

J Foot Ankle Surg 2017 Nov - Dec;56(6):1284-1287. Epub 2017 Jun 9.

Chair and Professor, Department of Orthopaedic Surgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.

Chondrolipoma is an extremely rare variant of lipoma with cartilaginous metaplasia. The presence of nonlipomatous components can lead to a variety of entities in the differential diagnosis from the radiologic findings. We describe an unusual case of a chondrolipoma occurring in the right ankle of a 9-year-old female. Physical examination showed a 3.5-cm, elastic-hard, poorly mobile, nontender mass adherent to the Achilles tendon. Plain radiographs revealed a faintly calcified soft tissue mass without bone involvement. Magnetic resonance imaging showed a well-defined mass with 2 components with heterogeneous signal intensity, suggesting the coexistence of a fatty area and another nonlipomatous component. Marginal excision of the tumor was performed. Histologically, the tumor was composed of mature adipose tissue studded with islands of mature hyaline cartilage. Based on these findings, the tumor was diagnosed as a chondrolipoma. The patient had no evidence of local recurrence within 9 months of follow-up. To the best of our knowledge, this is the first case of chondrolipoma originating from the ankle in a child.
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http://dx.doi.org/10.1053/j.jfas.2017.04.031DOI Listing
July 2018

Inflammatory Biomarkers in Cancer.

Mediators Inflamm 2016 23;2016:7282797. Epub 2016 Oct 23.

Department of Orthopaedic Surgery, Fukuoka University Graduate School of Medicine, Fukuoka, Japan.

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http://dx.doi.org/10.1155/2016/7282797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5097815PMC
May 2017

HR23b expression is a potential predictive biomarker for HDAC inhibitor treatment in mesenchymal tumours and is associated with response to vorinostat.

J Pathol Clin Res 2016 Apr 5;2(2):59-71. Epub 2016 Feb 5.

Institute of Pathology, University Hospital CologneCologneGermany; Institute of Pathology, University Hospital GöttingenGöttingenGermany.

Histone deacetylases (HDAC) are key players in epigenetic regulation of gene expression and HDAC inhibitor (HDACi) treatment seems to be a promising anticancer therapy in many human tumours, including soft tissue sarcomas. HR23b has been shown to be a potential biomarker for sensitivity to HDACi therapy in cutaneous T-cell lymphoma and hepatocellular carcinoma. We aimed to evaluate HR23b as a candidate biomarker for HDACi response in sarcomas and gastrointestinal stromal tumours (GIST). Therefore, HR23b expression was analysed comprehensively by western blot in sarcoma and GIST cell lines covering all major clinically relevant subtypes. MTT assay and ApoTox-Glo(TM) Triplex assay were performed after treatment with vorinostat, belinostat, mocetinostat and entinostat. HR23b protein expression was measured under HDACi treatment. Furthermore, HR23b expression levels were immunohistochemically determined in a large set of 523 clinical samples from sarcoma and GIST patients. Western blot analyses showed that sarcomas differ significantly in their expression of HR23b protein. All HDACi were able to regulate proliferation and apoptosis in vitro. Sensitivity to vorinostat correlated significantly with HR23b protein expression. Immunohistochemical prevalence screening in clinical samples of relevant adult-type tumours revealed that 12.5% of sarcomas (among them malignant peripheral nerve sheath tumours, pleomorphic liposarcomas, leiomyosarcomas, dedifferentiated liposarcomas, synovial sarcomas and angiosarcomas) and 23.2% of GIST show high HR23b expression. Therefore, HDACi have antiproliferative and proapoptotic effects in sarcomas depending on the expression level of HR23b. These findings suggest that HR23b represents a candidate biomarker for HDACi sensitivity in certain sarcoma types and in GIST.
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http://dx.doi.org/10.1002/cjp2.35DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4907056PMC
April 2016

Duplication of chromosome segment 12q13-15 in a lipomatous tumor with minimal nuclear atypia: A case report.

Oncol Lett 2016 Apr 7;11(4):2875-2878. Epub 2016 Mar 7.

Department of Orthopaedic Surgery, Faculty of Medicine, Fukuoka University, Fukuoka 814-0180, Japan.

Ordinary lipoma is cytogenetically characterized by structural rearrangements, particularly translocations, of 12q13-15. By contrast, atypical lipomatous tumors exhibit supernumerary ring or giant marker chromosomes that are composed mainly of amplified material from the 12q13-15 chromosome segment. The present study describes the cytogenetic and molecular cytogenetic findings from a lipomatous tumor with minimal nuclear atypia that was identified in a 49-year-old female patient. Magnetic resonance imaging of the right shoulder revealed a 13-cm fatty mass in the subcutaneous layer that possessed only pencil-line septa. Contrast-enhanced fat-suppressed T1-weighted images demonstrated faint enhancement. A marginal excision was performed. Histologically, the tumor was composed of lobules that consisted of mature adipocytes separated by thin fibrous septa. There was minimal nuclear atypia in certain cells, and a small number of binucleated cells were also observed within the tumor. Immunohistochemically, the tumor cells did not reveal the expression of murine double-minute 2 (MDM2). Cytogenetic analysis revealed a complex karyotype with several numerical and structural alterations, including 12q rearrangements. Spectral karyotyping demonstrated a duplication of chromosome segment 12q13-15. Interphase fluorescence hybridization analysis revealed no gene amplification. The present case indicates that duplication of 12q may be associated with minimal nuclear atypia in a subset of lipomatous tumors.
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http://dx.doi.org/10.3892/ol.2016.4305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4812505PMC
April 2016

Translocation (1;5) in a Glomus Tumor.

Anticancer Res 2015 Nov;35(11):6167-70

Department of Orthopaedic Surgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.

Glomus tumor is a rare perivascular neoplasm that usually occurs in the distal extremities of young adults. Recent molecular studies have identified microRNA 143-NOTCH fusions or NOTCH1-3 rearrangements in benign and malignant glomus tumors. Herein, we describe the cytogenetic and molecular cytogenetic findings of a glomus tumor arising in the left wrist of a 45-year-old man. Physical examination showed a 1.3-cm, blue-red, tender nodule. Magnetic resonance imaging demonstrated a subcutaneous, well-circumscribed mass with low signal intensity on T1-weighted sequences and high signal intensity on T2-weighted sequences. Contrast-enhanced fat-suppressed T1-weighted sequences showed a homogeneous, strong enhancement. A marginal excision was performed and histopathological examination confirmed the diagnosis of a glomus tumor. Cytogenetic and spectral karyotypic analyses showed a novel rearrangement involving chromosome bands 1p13 and 5q32. There has been no evidence of local recurrence four months after surgery. To the best of our knowledge, this is the first case of sporadic glomus tumor with t(1;5).
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November 2015

Periosteal chondroma of the distal tibia: Computed tomography and magnetic resonance imaging characteristics and correlation with histological findings.

Mol Clin Oncol 2015 May 22;3(3):677-681. Epub 2015 Jan 22.

Department of Orthopaedic Surgery, Faculty of Medicine, Fukuoka University, Fukuoka 814-0180, Japan.

Periosteal chondroma is a rare benign hyaline cartilage neoplasm situated on the bone surface. This is the presentation of a unique case of periosteal chondroma arising in the left distal tibial metaphysis of a 25-year-old female patient with a history of antecedent trauma. The physical examination revealed swelling and tenderness in the anterolateral aspect of the left distal lower limb. Plain radiographs revealed a discernible soft tissue lesion with peripheral foci of mineralization. Computed tomography scans confirmed the presence of a surface-based mass with peripheral ossification and a thin rim of calcification. On magnetic resonance imaging, the well-circumscribed mass exhibited intermediate signal intensity on T1-weighted sequences and high signal intensity with foci of decreased signal intensity on T2-weighted sequences. Contrast-enhanced T1-weighted sequences revealed predominantly peripheral enhancement without intramedullary involvement. Following an open biopsy, marginal excision with curettage of the underlying bone cortex was performed. Histologically, the tumor consisted of mature hyaline cartilage arranged in distinct lobules. Foci of ossification with mature bone trabeculae forming a thin shell-like structure were identified in the periphery of the tumor. The mindbomb E3 ubiquitin protein ligase 1 labeling index was <1%. Based on these findings, the tumor was diagnosed as periosteal chondroma. There has been no evidence of local recurrence at 4 months following surgery. Despite its rarity, periosteal chondroma must be considered as a possible diagnosis when confronted with a surface-based, mineralized lesion in the metaphysis of long bones.
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http://dx.doi.org/10.3892/mco.2015.492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4471519PMC
May 2015

Successful enucleation of large multinodular/plexiform schwannoma of the foot and ankle.

Springerplus 2015 17;4:260. Epub 2015 Jun 17.

Department of Orthopaedic Surgery, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180 Japan.

Background: It is often challenging to completely resect multinodular/plexiform schwannomas involving important deep nerves using minimally invasive surgically techniques.

Case Description: A 32-year-old woman presented with a 5-year history of a slowly growing, painful mass in the medial aspect of the right ankle. Magnetic resonance imaging (MRI) demonstrated multiple nodular lesions with iso-signal intensity relative to skeletal muscle on T1-weighted sequences and heterogeneous high signal intensity on T2-weighted sequences. Mild to moderate enhancement was identified after gadolinium administration. All 58 tumors were completely enucleated using an intracapsular technique. Histological examination confirmed the diagnosis of schwannoma consisting mainly of Antoni A areas. The burning sensation was relieved immediately after surgery. The patient had no aggravated neurological deficit and was very satisfied with the outcome of the treatment at final follow-up.

Discussion And Evaluation: We experienced a very rare case of a large multinodular/plexiform schwannoma arising from the posterior tibial nerve and its larger terminal branch. Our case had the characteristic MRI features of this condition. It is extremely important to differentiate multinodular/plexiform schwannoma from plexiform neurofibroma and malignant peripheral nerve sheath tumor, with complete surgical enucleation being curative.

Conclusions: MRI is a clinically useful modality in the evaluation and detection of deep-seated multinodular/plexiform schwannoma. Intracapsular enucleation seems to be an acceptable treatment for this peculiar tumor located in the foot and ankle.
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http://dx.doi.org/10.1186/s40064-015-1087-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4469603PMC
June 2015

SRC inhibition represents a potential therapeutic strategy in liposarcoma.

Int J Cancer 2015 Dec 6;137(11):2578-88. Epub 2015 Jul 6.

Department of Pathology, University Hospital Cologne, Cologne, Germany.

Liposarcomas (LS) are the most common malignant mesenchymal tumors, with an overall long-term mortality rate of 60%. LS comprise three major subtypes, i.e., well-differentiated/dedifferentiated liposarcoma (WDLS/DDLS), myxoid/round cell liposarcoma (MLS) and pleomorphic liposarcoma (PLS). Aiming at the preclinical identification of novel therapeutic options, we here investigate the functional significance of SRC in primary human LS and in LS-derived cell lines. Immunohistochemical and Western blot analyses reveal relevant levels of activated p-(Tyr416)-SRC in LS of the different subtypes with particular activation in MLS and PLS. Dysregulation of the SRC modifiers CSK and PTP1B was excluded as major reason for the activation of the kinase. Consistent siRNA-mediated knockdown of SRC or inhibition by the SRC inhibitor Dasatinib led to decreased proliferation of LS cell lines of the different subtypes, with MLS cells reacting particularly sensitive in MTT assays. Flow cytometric analyses revealed that this effect was due to a significant decrease in mitotic activity and an induction of apoptosis. SRC inhibition by Dasatinib resulted in dephosphorylation of SRC itself, its interacting partners FAK and IGF-IR as well as its downstream target AKT. Consistent with a particular role of SRC in cell motility, Dasatinib reduced the migratory and invasive potential of MLS cells in Boyden chamber and Matrigel chamber assays. In summary, we provide evidence that SRC activation plays an important role in LS biology and therefore represents a potential therapeutic target, particularly in MLS and PLS.
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http://dx.doi.org/10.1002/ijc.29645DOI Listing
December 2015

FDG PET/CT and MR imaging of CD34-negative soft-tissue solitary fibrous tumor with NAB2-STAT6 fusion gene.

Anticancer Res 2015 Feb;35(2):967-71

Department of Orthopaedic Surgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.

Extrapleural solitary fibrous tumor (SFT) is an uncommon mesenchymal neoplasm of intermediate biological potential. Herein, we describe the radiological, histological, immunohistochemical and molecular genetic features of an SFT arising in the left thigh of a 55-year-old woman. Magnetic resonance imaging exhibited a well-defined mass with intermediate signal intensity on T1-weighted sequences and heterogeneous high signal intensity on T2-weighted sequences. Contrast-enhanced T1-weighted sequences showed strong homogeneous enhancement of the mass. A prominent vascular pedicle was visible. Integrated positron-emission tomography (PET)/computed tomographic (CT) scan demonstrated a moderate 18F-fluorodeoxyglucose (FDG) uptake (maximum standardized uptake value, 4.45) in the mass. Following an open biopsy, wide excision of the tumor was performed. Histologically, the tumor was composed of a proliferation of spindle cells in a fibrous stroma with focal hyalinization. Thin-walled branching hemangiopericytoma-like vessels were observed. Immunohistochemically, the tumor cells were diffusely positive for signal transducer and activator of transcription 6 (STAT6) but negative for CD34. The MIB-1 labeling index was less than 5%. Subsequent reverse transcriptase-polymerase chain reaction analysis identified a nerve growth factor inducible-A binding protein 2-STAT6 gene fusion. Our case supports the utility of STAT6 immunohistochemistry as an adjunct in the diagnosis of soft-tissue SFT with loss of CD34 positivity. To the best of our knowledge, this is the first report showing the FDG PET/CT findings of soft-tissue SFT.
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February 2015

Extensive lipoma-like changes of myxoid liposarcoma: morphologic, immunohistochemical, and molecular cytogenetic analyses.

Virchows Arch 2015 Apr 4;466(4):453-64. Epub 2015 Feb 4.

Department of Pathology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan,

Myxoid liposarcomas (MLSs) with extensive lipoma-like changes (MLSLC) are rare, and it is often difficult to distinguish them from well-differentiated liposarcoma (LS)/dedifferentiated LS (WDLS/DDLS) with myxoid changes. For the characterization of these neoplasms, we studied 8 MLSLCs, 11 ordinary MLSs, 4 WDLSs, and 6 DDLSs. Cytogenetically, MLSLC and ordinary MLS were characterized by t(12;16)(q13;p11) and FUS-DDIT3 fusion gene, whereas WDLS/DDLS lacked the fusion gene but possessed giant marker/ring chromosomes. Both lipoma-like and myxoid components of the same MLSLC exhibited the identical FUS-DDIT3, as confirmed by fluorescence in situ hybridization (FISH) and reverse transcription polymerase chain reaction (RT-PCR). Immunohistochemically, MDM2 and CDK4 were positive in WDLS/DDLS but negative in MLSLC and ordinary MLS. PPARγ, C/EBPα, adipophilin, and perilipin were found in each type of LS. Adipophilin was expressed chiefly in tiny fat droplets of immature lipoblasts, whereas perilipin showed a strong positive staining in large fat vacuoles of signet ring and multivacuolated lipoblasts. The Ki-67 labeling index was lower in the lipoma-like component of MLSLC when compared with the myxoid component of the same tumors as well as ordinary MLS (p < 0.001). When compared with ordinary MLS, MLSLC may be less aggressive in clinical behavior (rare recurrences or metastases) after a wide surgical excision. In conclusion, the distinction between MLSLC and WDLS/DDLS is important, because of the differences of molecular cytogenetic features as well as clinical behaviors between these distinct sarcomas presenting similar morphologic features. In addition, the combined immunohistochemical detection of adipophilin and perilipin may provide a useful ancillary tool for identification of lipoblastic cells in soft tissue sarcomas.
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http://dx.doi.org/10.1007/s00428-015-1721-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392166PMC
April 2015

Immunohistochemical, cytogenetic, and molecular cytogenetic characterization of both components of a dedifferentiated liposarcoma: implications for histogenesis.

Anticancer Res 2015 Jan;35(1):345-50

Department of Orthopaedic Surgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.

Dedifferentiated liposarcoma (DDLS) is a malignant adipocytic tumor showing transition from an atypical lipomatous tumor (ALT)/well-differentiated liposarcoma (WDLS) to a non-lipogenic sarcoma of variable histological grades. We present the immunohistochemical, cytogenetic, and molecular cytogenetic findings of DDLS arising in the right chest wall of a 76-year-old man. Magnetic resonance imaging exhibited a large mass composed of two components with heterogeneous signal intensities, suggesting the coexistence of a fatty area and another soft tissue component. The grossly heterogeneous mass was histologically composed of an ALT/WDLS component transitioning abruptly into a dedifferentiated component. Immunohistochemistry was positive for murine double-minute 2 (MDM2), cyclin-dependent kinase 4 (CDK4), and p16 in both components, although a more strong and diffuse staining was found in the dedifferentiated area. The MIB-1 labeling index was extremely higher in the dedifferentiated area compared to the ALT/WDLS area. Cytogenetic analysis of the ALT/WDLS component revealed the following karyotype: 46,X,-Y,+r. Notably, cytogenetic analysis of the dedifferentiated component revealed a similar but more complex karyotype. Spectral karyotyping demonstrated that the ring chromosome was entirely composed of material from chromosome 12. Interphase fluorescence in situ hybridization analysis revealed amplification of MDM2 and CDK4 in both components. These findings suggest that multiple abnormal clones derived from a single precursor cell would be present in DDLS, with one or more containing supernumerary rings or giant marker chromosomes.
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January 2015

Giant cell tumor of the patella: An uncommon cause of anterior knee pain.

Mol Clin Oncol 2015 Jan 1;3(1):207-211. Epub 2014 Oct 1.

Departments of Orthopaedic Surgery and Fukuoka University, Fukuoka 814-0180, Japan.

The patella is a rare site for the development of primary tumors. This is the case report of a giant cell tumor (GCT) occurring in the patella in a 25-year-old woman. The patient presented with a 1-year history of occasional right anterior knee pain. The radiological characteristics suggested a benign condition. The intraoperative pathological diagnosis was GCT of the bone. The lesion was treated by radical curettage with adjuvant therapy comprising phenol and ethanol and injection of calcium phosphate cement. Histologically, the tumor consisted of round or spindle-shaped mononuclear cells admixed with numerous osteoclastic giant cells. The patient was asymptomatic and there was no evidence of local recurrence or distant metastasis 16 months after surgery. Although rare, patellar GCT may be included in the differential diagnosis of anterior knee pain and/or swelling, particularly in young adults.
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http://dx.doi.org/10.3892/mco.2014.433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4251109PMC
January 2015

Fibroma of tendon sheath with 11q rearrangements.

Anticancer Res 2014 Sep;34(9):5159-62

Department of Orthopaedic Surgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.

Fibroma of tendon sheath is an uncommon, benign fibroblastic tumor that usually occurs in the upper extremities of young and middle-aged adults. A clonal chromosomal aberration, t(2;11)(q31-32;q12), has been described in one case. We herein present a unique cytogenetic finding of fibroma of tendon sheath arising in the first web space of the right hand of a 38-year-old woman. Physical examination showed a 3.5-cm, firm, mobile, non-tender mass. Magnetic resonance imaging showed a well-defined soft tissue mass with iso- to slightly-low signal intensity relative to skeletal muscle on both T1- and T2-weighted sequences. Contrast-enhanced T1-weighted sequences demonstrated moderate patchy enhancement of the mass. A fibroma or giant cell tumor of tendon sheath was suggested, and the lesion was marginally excised. Histological examination confirmed the diagnosis of fibroma of tendon sheath. Cytogenetic analysis revealed a novel t(9;11)(p24;q13-14) translocation among other karyotypic abnormalities. The postoperative course was uneventful, and the patient is doing well without local recurrence two months after surgery. To the best of our knowledge, this is only the second report of fibroma of tendon sheath with clonal chromosomal abnormalities.
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September 2014

Diffuse-type tenosynovial giant cell tumor with t(1;17)(p13;p13) and trisomy 5.

In Vivo 2014 Sep-Oct;28(5):949-52

Department of Orthopaedic Surgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.

Diffuse-type tenosynovial giant cell tumor (TSGCT) is a locally aggressive neoplasm that primarily affects the synovium and tendon sheath in young adults. Rearrangement of chromosome band 1p13 is now considered a characteristic genetic feature of TSGCT, with the most frequent chromosomal alteration t(1;2)(p13;q37). Here, we describe a unique cytogenetic finding of diffuse-type TSGCT arising in the ankle of an 18-year-old woman. Magnetic resonance imaging demonstrated an ill-defined juxta-articular mass with decreased signal intensity on both T1- and T2-weighted images. Contrast-enhanced T1-weighted images showed intense enhancement of the mass. Open complete resection was performed. Histologically, the tumor was composed of mononuclear cells admixed with multi-nucleated osteoclast-like giant cells, foam cells, siderophages and inflammatory cells. Cytogenetic analysis revealed a reciprocal translocation involving chromosomes 1 and 17, concomitant with a few other numerical and structural alterations. In addition, trisomy 5 as the sole anomaly was identified in two metaphase cells. To the best of our knowledge, this is the first report of this neoplasm with t(1;17)(p13;p13).
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May 2015

Calcifying aponeurotic fibroma of the finger in an elderly patient: CT and MRI findings with pathologic correlation.

Exp Ther Med 2014 Sep 11;8(3):841-843. Epub 2014 Jul 11.

Department of Orthopaedic Surgery, Faculty of Medicine, Fukuoka University, Fukuoka 814-0180, Japan.

Calcifying aponeurotic fibroma (CAF) is a rare, locally aggressive fibroblastic lesion that occurs predominantly in the distal extremities of children and adolescents. In the present study, a case of pathologically proven CAF arising in the right little finger of a 69-year-old woman is presented. Physical examination revealed a firm, immobile, non-tender mass. Plain radiographs showed a faintly calcified soft tissue mass without bone involvement and computed tomography scans clearly demonstrated the presence of the lesion. Magnetic resonance imaging revealed that the lesion exhibited low to intermediate signal intensity on T1-weighted images and heterogeneous high signal intensity with small foci of low signal intensity on T2-weighted spectral presaturation with inversion recovery images. Contrast-enhanced fat-suppressed T1-weighted images demonstrated intense heterogeneous enhancement throughout the mass. The patient underwent an excisional biopsy. Histologically, the tumor showed a biphasic pattern, composed of a moderately cellular fibromatosis-like component and irregular calcified areas with polygonal epithelioid cells. There has been no evidence of local recurrence four months following surgery. To the best of our knowledge, this case report describes the oldest patient with this condition.
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http://dx.doi.org/10.3892/etm.2014.1838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4113653PMC
September 2014

Atypical lipomatous tumor with structural rearrangements involving chromosomes 3 and 8.

Anticancer Res 2014 Jun;34(6):3073-6

Department of Orthopaedic Surgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.

Atypical lipomatous tumor (ALT) is an intermediate (locally aggressive) mesenchymal neoplasm with the potential to dedifferentiate to higher grades over time. It is cytogenetically characterized by the presence of one or more supernumerary ring and giant marker chromosomes. These abnormal chromosomes invariably contain amplified sequences derived from the 12q14-15 region. We describe a unique cytogenetic finding of ALT arising in the right lower back of a 42-year-old man. Magnetic resonance imaging demonstrated a predominantly fatty mass with irregularly thickened, linear, swirled, and nodular septa. Contrast-enhanced fat-suppressed T1-weighted images showed significant enhancement of the non-adipose areas. A sub-extensive resection was performed. Histologically, the tumor consisted predominantly of mature fat cells with atypical stromal cells and multivacuolated lipoblasts. Immunohistochemically, the tumor cells were positive for p16 (diffuse and strong signal) and cyclin-dependent kinase-4 (focal and weak signal) but negative for murine double-minute 2. Cytogenetic analysis displayed a t(3;8)(q28;q13) translocation as the sole anomaly or concomitant with a few other numerical and structural alterations. There has been no evidence of local recurrence two months after surgery. To the best of our knowledge, this is the first case of ALT with structural aberrations involving chromosomes 3 and 8, associated with an absence of 12q rearrangements.
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June 2014

Imaging features of periosteal chondroma manifesting as a subcutaneous mass in the index finger.

Case Rep Orthop 2014 23;2014:763480. Epub 2014 Feb 23.

Department of Orthopaedic Surgery, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.

Periosteal chondroma is a rare benign hyaline cartilage neoplasm that occurs most commonly in the metaphases of long tubular bones. We present a unique case of periosteal chondroma arising in the proximal phalanx of the left index finger in a 12-year-old boy. Physical examination revealed a slightly protuberant, subcutaneous mass. Plain radiographs and computed tomography scans showed a periosteal lesion producing saucerization of the cortex and subjacent cortical sclerosis, without internal matrix calcification. On magnetic resonance imaging, the lesion exhibited intermediate signal intensity on T1-weighted images and high signal intensity on T2-weighted images. Contrast-enhanced fat-suppressed T1-weighted images demonstrated peripheral and septal enhancement. The patient underwent a marginal excision with curettage of the underlying bone cortex. Histological examination confirmed the diagnosis of periosteal chondroma. There has been no evidence of local recurrence eight months after surgery. Periosteal chondroma can protrude into the subcutaneous soft tissue causing a palpable mass. Recognition of the typical radiological features can lead to an accurate diagnosis of this rare condition.
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http://dx.doi.org/10.1155/2014/763480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3978408PMC
April 2014

Osteosarcoma of the patella mimicking giant cell tumor: imaging features with histopathological correlation.

Anticancer Res 2014 May;34(5):2541-5

Department of Orthopaedic Surgery, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.

Patellar tumors represent an uncommon etiology of anterior knee pain and their diagnosis is often delayed. We present an unusual case of conventional osteosarcoma arising in the patella of a 47-year-old man. The patient presented with a 1-year history of increasing anterior knee pain and swelling. Plain radiographs revealed a multi-locular lytic lesion in the inferolateral side of the patella. Computed tomography scans demonstrated an intraosseous lytic lesion with cortical thinning/breakthrough anteriorly. On magnetic resonance imaging, the lesion exhibited low signal intensity on T1-weighted images and heterogeneous high signal intensity on T2-weighted images. Fluid-fluid levels were also observed on T2-weighted images. Contrast-enhanced fat-suppressed T1-weighted images demonstrated strong enhancement of the lesion. These imaging features were suggestive of a benign condition; however, the diagnosis of osteosarcoma was confirmed by histopathology. After neoadjuvant chemotherapy, a wide resection with a free anterolateral thigh flap was performed. The patient subsequently underwent adjuvant chemotherapy and had no evidence of local recurrence or distant metastasis six months after surgery. Our case highlights the difficulty in the diagnosis of patellar osteosarcoma and the importance of performing a biopsy before definitive treatment.
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May 2014

Soft tissue perineurioma of the foot with 10q24 rearrangements: unique MRI features with histopathologic correlation.

Skeletal Radiol 2014 Jul 22;43(7):1017-22. Epub 2014 Feb 22.

Department of Orthopaedic Surgery, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan,

Perineurioma is an uncommon benign peripheral nerve sheath tumor with advanced perineurial differentiation. Two distinct subtypes are recognized: intraneural and soft tissue. We herein present a unique case of soft tissue perineurioma in the right foot of a 43-year-old man. Radiographs showed a non-specific soft tissue mass. On computed tomography scan, the mass was iso- to slightly hypodense relative to muscle. On T1- and T2-weighted images, the mass exhibited iso- to slightly low signal intensity relative to muscle with foci of high signal intensity. Slight contrast enhancement was noted on enhanced T1-weighted images with fat suppression. A marginal excision of the tumor was performed and histopathologic examination confirmed the diagnosis of soft tissue perineurioma. The clinicopathologic, radiologic, and cytogenetic findings are described, and the relevant literature is reviewed.
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http://dx.doi.org/10.1007/s00256-014-1839-0DOI Listing
July 2014

High expression of CD109 antigen regulates the phenotype of cancer stem-like cells/cancer-initiating cells in the novel epithelioid sarcoma cell line ESX and is related to poor prognosis of soft tissue sarcoma.

PLoS One 2013 20;8(12):e84187. Epub 2013 Dec 20.

Department of Pathology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan.

Epithelioid sarcoma (ES) is a relatively rare, highly malignant soft tissue sarcoma. The mainstay of treatment is resection or amputation. Currently other therapeutic options available for this disease are limited. Therefore, a novel therapeutic option needs to be developed. In the present study, we established a new human ES cell line (ESX) and analyzed the characteristics of its cancer stem-like cells/cancer-initiating cells (CSCs/CICs) based on ALDH1 activity. We demonstrated that a subpopulation of ESX cells with high ALDH1 activity (ALDH(high) cells) correlated with enhanced clonogenic ability, sphere-formation ability, and invasiveness in vitro and showed higher tumorigenicity in vivo. Next, using gene expression profiling, we identified CD109, a GPI-anchored protein upregulated in the ALDH(high) cells. CD109 mRNA was highly expressed in various sarcoma cell lines, but weakly expressed in normal adult tissues. CD109-positive cells in ESX predominantly formed spheres in culture, whereas siCD109 reduced ALDH1 expression and inhibited the cell proliferation in vitro. Subsequently, we evaluated the expression of CD109 protein in 80 clinical specimens of soft tissue sarcoma. We found a strong correlation between CD109 protein expression and the prognosis (P = 0.009). In conclusion, CD109 might be a CSC/CIC marker in epithelioid sarcoma. Moreover, CD109 is a promising prognostic biomarker and a molecular target of cancer therapy for sarcomas including ES.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0084187PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3869840PMC
October 2014
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