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      The Role of Osteocalcin and Alkaline Phosphatase Immunohistochemistry in Osteosarcoma Diagnosis

      research-article
      , , ,
      Pathology Research International
      Hindawi

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          Abstract

          Background

          The diagnosis of Osteosarcoma (OSA) is not always straightforward. OSA may resemble Other Primary Bone Tumours (OPBT). The diagnosis of osteosarcoma is sometimes difficult especially in a very small specimen. Immunohistochemistry is one of ancillary testing types that can help the diagnosis of many tumours. The aim of this study was to evaluate the validity of Osteocalcin (OCN) and Alkaline Phosphatase (ALP) immunohistochemistry in discriminating OSA from OPBT.

          Method

          This study included 50 selected human primary bone tumours, 25 cases of OSA and 25 cases of OPBT. Immunohistochemical evaluation of OCN and ALP was done for all cases. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy were calculated.

          Result

          The mean age of OSA and OPBT patients was 19.6 ± 13.6 and 40.0 ± 16.3 years, respectively. Osteocalcin was positive in 17/25 (68%) cases of OSA and 16/25 (64%) cases of OPBT ( p = 0.061). Alkaline Phosphatase was positive in 24/25 (96%) cases of OSA and 5/25 (20%) cases of OPBT ( p < 0.001). The sensitivity of OCN in OSA diagnosis was 68%, with specificity, PPV, NPV, and overall accuracy being 36%, 52%, 53%, and 52%, respectively. The sensitivity of ALP in OSA diagnosis was 96%, with specificity, PPV, NPV, and overall accuracy being 80%, 82.7%, 95.2%, and 88%, respectively.

          Conclusion

          ALP immunohistochemistry is useful in discriminating OSA from OPBT. ALP is superior to OCN in OSA diagnosis. OCN cannot be used to differentiate between OSA and OPBT.

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          Most cited references17

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          Comparative review of human and canine osteosarcoma: morphology, epidemiology, prognosis, treatment and genetics

          Osteosarcoma (OSA) is a rare cancer in people. However OSA incidence rates in dogs are 27 times higher than in people. Prognosis in both species is relatively poor, with 5 year OSA survival rates in people not having improved in decades. For dogs, 1 year survival rates are only around ~ 45%. Improved and novel treatment regimens are urgently required to improve survival in both humans and dogs with OSA. Utilising information from genetic studies could assist in this in both species, with the higher incidence rates in dogs contributing to the dog population being a good model of human disease. This review compares the clinical characteristics, gross morphology and histopathology, aetiology, epidemiology, and genetics of canine and human OSA. Finally, the current position of canine OSA genetic research is discussed and areas for additional work within the canine population are identified.
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            Osteocalcin Mediates Biomineralization during Osteogenic Maturation in Human Mesenchymal Stromal Cells

            There is a growing interest in cell therapies using mesenchymal stromal cells (MSCs) for repairing bone defects. MSCs have the ability to differentiate into osteoprogenitors and osteoblasts as well as to form calcified bone matrix. However, the molecular mechanisms governing mineralization during osteogenic differentiation remain unclear. Non-collagenous proteins in the extracellular matrix are believed to control different aspects of the mineralization. Since osteocalcin is the most abundant non-collagenous bone matrix protein, the purpose of this study is to investigate the roles of osteocalcin in mineral species production during osteogenesis of MSCs. Using Raman spectroscopy, we found that the maturation of mineral species was affected by osteocalcin expression level. After osteocalcin was knocked down, the mineral species maturation was delayed and total hydroxyapatite was lower than the control group. In addition, the expression of osteogenic marker genes, including RUNX2, alkaline phosphatase, type I collagen, and osteonectin, was downregulated during osteogenic differentiation compared to the control group; whereas gene expression of osterix was upregulated after the knockdown. Together, osteocalcin plays an essential role for the maturation of mineral species and modulates osteogenic differentiation of MSCs. The results offer new insights into the enhancement of new bone formation, such as for the treatments of osteoporosis and fracture healing.
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              High serum alkaline phosphatase cooperating with MMP-9 predicts metastasis and poor prognosis in patients with primary osteosarcoma in Southern China

              Background Osteosarcoma is a malignant tumor with high ability to form invasion and metastasis. Identifying prognostic factor in osteosarcoma is helpful to select those patients for more aggressive management. Our study evaluated serum alkaline phosphatase (ALP) cooperating with matrix metalloproteinase-9 (MMP-9) as an important prognostic predictor for local recurrence and distant metastasis of osteosarcoma. Methods 177 cases were included from the osteosarcoma patients treated at 1st Affiliated Hospital of Sun Yat-sen University (1999-2008). Pre-chemotherapy serum ALP (pre-ALP) were studied and correlated with tumor recurrence, lung metastasis and patient survival. MMP-9 protein in tumor tissues was detected by immunohistochemistry and correlated with pre-ALP level. Results Pre-ALP were partitioned into normal, high, and very high groups, in each group the incidence of metastases was 12.2%, 21.2% and 34.6%, respectively (p = 0.007). In the three groups the mean disease-free survival (DFS) was 57 ± 3.15, 28 ± 3.57 and 14 ± 3.35 months, respectively (p < 0.001); overall survival (OS) was 92 ± 26.89, 39 ± 8.61 and 17 ± 5.07 months, respectively (p < 0.001). By multivariate analysis, elevated serum pre-ALP were associated with shorter DFS (p = 0.018) and OS (p = 0.031). If elevated ALP levels decreased after clinical treatment, the incidence of lung metastasis rate decreased (p = 0.028); DFS and OS were both prolonged (p < 0.001). Pre-ALP was also positively correlated with MMP-9 expression (p = 0.015) in tumor tissue. Conclusions Pre-ALP was an independent prognostic factor for the survival of osteosarcoma patients in south China, and correlated with MMP-9 expression and lung metastasis. ALP can also serve as a prognostic marker for treatment, and merit large-scale validation studies.
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                Author and article information

                Contributors
                Journal
                Patholog Res Int
                Patholog Res Int
                PRI
                Pathology Research International
                Hindawi
                2090-8091
                2042-003X
                2018
                3 May 2018
                : 2018
                : 6346409
                Affiliations
                Department of Anatomical Pathology, Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin General Hospital, Bandung, Indonesia
                Author notes

                Academic Editor: Piero Tosi

                Author information
                http://orcid.org/0000-0001-8817-6753
                http://orcid.org/0000-0003-3872-6627
                Article
                10.1155/2018/6346409
                5960576
                29854380
                23d939f9-90de-46ca-85ec-6f12914abfb0
                Copyright © 2018 Hasrayati Agustina et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 14 December 2017
                : 10 March 2018
                : 28 March 2018
                Categories
                Research Article

                Pathology
                Pathology

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