Overexpression of Metastatic Tumor Antigen in Osteosarcoma: Comparison between Conventional High-Grade and Central Low-Grade Osteosarcoma

Hye-Rim Park,Woon Won Jung,Hyun Sook Kim,Patrizia Bacchini,Franco Bertoni,Yong-Koo Park 대한암학회 2005 Cancer Research and Treatment Vol.37 No.6

Purpose: The metastatic tumor antigen (MTA) gene is a recently identified metastasis-associated gene which has implications in the signal transduction or regulation of gene expression. However, the expression of MTA in osteosarcoma and its potential relationship with metastasis have not been examined, forming the basis of this study.Materials and Methods: We compared the expression levels of the MTA1 protein between 32 cases of highgrade osteosarcomas and 21 cases of low-grade osteosarcomas by immunohistochemistry. In addition, the mRNA expression levels of MTA1, 2, 3 in these osteosarcoma cell lines and control fibroblasts were evaluated by real-time quantitative PCR.Results: MTA1 immunoreactivity was present in 81.25% of high-grade osteosarcoma specimens. Its expression was predominantly localized to the nucleus or cytoplasm of osteosarcoma cells. Thirteen (86.6%) of 15 patients who died of osteosarcomas displayed strong MTA1 expression. Both primary bone and pulmonary metastatic lesions exhibited MTA1 expression. All lowgrade osteosarcomas were negative for MTA1 except for focal weak reactivity in two cases. The tested high-grade osteosarcoma cell lines showed marked amplification of MTA1 and MTA2 mRNA compared to control cells. Conclusion: These results suggest that MTA might be involved in the progression of high-grade osteosarcoma, particularly in hematogenous metastasis of osteosarcoma.

Expression of heat shock proteins in osteosarcomas

Moon, Ahrim,Bacchini, Patrizia,Bertoni, Franco,Olvi, Liliana G.,Santini-Arawo, Eduardo,Kim, Youn Wha,Park, Yong-Koo Elsevier 2010 Pathology Vol.42 No.5

<P>Aims: Heat shock proteins (HSPs) protect cells against stress-associated injuries and are overexpressed in several malignant tumours. We investigated the potential roles of HSP27, HSP60, and HSP70 in conventional and low grade central osteosarcoma. Methods: Expressions of HSP27, HSP60, and HSP70 were analysed using immunohistochemistry on tissue sections from 52 cases of conventional osteosarcoma and 21 cases of low grade central osteosarcoma. We evaluated the expression of each protein and examined its relationship with clinicopathological parameters. Results: We found significantly different expressions of HSP27 and HSP70 between conventional and low grade central osteosarcoma [34.6% versus 4.8% (p = 0.008), 88.5% versus 14.3% (p < 0.001)]. However, HSP60 was highly expressed in both kinds of osteosarcoma (92.3% versus 85.7%). In conventional osteosarcoma, a higher expression of HSP27 was significantly related to distant metastasis (p = 0.034) and histological subtype [osteoblastic versus non-osteoblastic (p = 0.041)]. The expressions of HSP60 and HSP70 were not significantly related to any tested clinicopathological parameter. Conclusions: HSP27 and HSP70 may be used as differential markers to distinguish conventional and low grade central osteosarcoma. HSP27 may be used as a possible prognostic marker in conventional osteosarcoma cases.</P>

Expression of Carbonic Anhydrase IX Correlates with Histologic Grade and Metastasis in Osteosarcoma

박용구,박혜림,서진원,Patrizia Bacchini,Franco Bertoni 대한병리학회 2010 Journal of Pathology and Translational Medicine Vol.44 No.4

Background : Carbonic anhydrase IX (CA9) is reportedly overexpressed in several types of carcinomas, but little is known about the expression pattern of CA9 in osteosarcoma. We aimed to assess the prevalence of CA9 expression and its prognostic implications in osteosarcoma patients. Methods : We compared immunohistochemical expression of CA9 between conventional, high-grade and low-grade, central osteosarcomas. Specimens were obtained before chemotherapy and stained with anti-human CA9 antibody. We also evaluated the histologic grade, presence of metastasis, and patient prognosis. Results : Among 38 samples of conventional high-grade osteosarcoma, 22 (57.9%) tumors displayed CA9 overexpression. Twenty-five cases of low-grade central osteosarcomas were all negative (p < 0.0001). CA9 expression was significantly associated with the presence of metastasis (p = 0.0010). The overall survival rate was significantly reduced with increased CA9 expression (p = 0.0012), higher histologic grade (p < 0.0001), and younger age (p = 0.0140). However, the overall survival rate was not significantly correlated with gender, tumor size, or American Joint Committee on Cancer stage. Conclusions : CA9 expression is a frequent and tumor-specific event in osteosarcoma. CA9 expression is associated with higher grade tumors, metastasis and poor prognosis for the osteosarcoma patients.

Syndecan-4 and fibronectin in osteosarcoma

Na, Ki Yong,Bacchini, Patrizia,Bertoni, Franco,Kim, Youn Wha,Park, Yong-Koo Elsevier Science B.V., Amsterdam 2012 Pathology Vol.44 No.4

Computer-aided design/computer-aided manufacturing of hydroxyapatite scaffolds for bone reconstruction in jawbone atrophy: a systematic review and case report

Garagiola, Umberto,Grigolato, Roberto,Soldo, Rossano,Bacchini, Marco,Bassi, Gianluca,Roncucci, Rachele,De Nardi, Sandro Korean Association of Maxillofacial Plastic and Re 2016 Maxillofacial Plastic Reconstructive Surgery Vol.38 No.-

Background: We reviewed the biological and mechanical properties of porous hydroxyapatite (HA) compared to other synthetic materials. Computer-aided design/computer-aided manufacturing (CAD/CAM) was also evaluated to estimate its efficacy with clinical and radiological assessments. Method: A systematic search of the electronic literature database of the National Library of Medicine (PubMed-MEDLINE) was performed for articles published in English between January 1985 and September 2013. The inclusion criteria were (1) histological evaluation of the biocompatibility and osteoconductivity of porous HA in vivo and in vitro, (2) evaluation of the mechanical properties of HA in relation to its porosity, (3) comparison of the biological and mechanical properties between several biomaterials, and (4) clinical and radiological evaluation of the precision of CAD/CAM techniques. Results: HA had excellent osteoconductivity and biocompatibility in vitro and in vivo compared to other biomaterials. HA grafts are suitable for milling and finishing, depending on the design. In computed tomography, porous HA is a more resorbable and more osteoconductive material than dense HA; however, its strength decreases exponentially with an increase in porosity. Conclusions: Mechanical tests showed that HA scaffolds with pore diameters ranging from 400 to $1200{\mu}m$ had compressive moduli and strength within the range of the human craniofacial trabecular bone. In conclusion, using CAD/CAM techniques for preparing HA scaffolds may increase graft stability and reduce surgical operating time.

Computer-aided design/computer-aided manufacturing of hydroxyapatite scaffolds for bone reconstruction in jawbone atrophy: a systematic review and case report

Umberto Garagiola,Roberto Grigolato,Rossano Soldo,Marco Bacchini,Gianluca Bassi,Rachele Roncucci,Sandro De Nardi 대한악안면성형재건외과학회 2015 Maxillofacial Plastic Reconstructive Surgery Vol.37 No.-

Background: We reviewed the biological and mechanical properties of porous hydroxyapatite (HA) compared toother synthetic materials. Computer-aided design/computer-aided manufacturing (CAD/CAM) was also evaluated toestimate its efficacy with clinical and radiological assessments. Method: A systematic search of the electronic literature database of the National Library of Medicine (PubMed-MEDLINE) was performed for articles published in English between January 1985 and September 2013. The inclusioncriteria were (1) histological evaluation of the biocompatibility and osteoconductivity of porous HA in vivo and in vitro,(2) evaluation of the mechanical properties of HA in relation to its porosity, (3) comparison of the biological andmechanical properties between several biomaterials, and (4) clinical and radiological evaluation of the precision ofCAD/CAM techniques. Results: HA had excellent osteoconductivity and biocompatibility in vitro and in vivo compared to other biomaterials. HA grafts are suitable for milling and finishing, depending on the design. In computed tomography, porous HA is amore resorbable and more osteoconductive material than dense HA; however, its strength decreases exponentiallywith an increase in porosity. Conclusions: Mechanical tests showed that HA scaffolds with pore diameters ranging from 400 to 1200 μm hadcompressive moduli and strength within the range of the human craniofacial trabecular bone. In conclusion, usingCAD/CAM techniques for preparing HA scaffolds may increase graft stability and reduce surgical operating time.

Differential Expression of CXCR4 in Conventional High-grade and Low-grade Central Osteosarcoma and Its Prognostic Implications

박혜림,서진원,박용구,Park, Hye-Rim,Seo, Jin-Won,Bacchini, Patrizia,Bertoni, Franco,Park, Yong-Koo The Korean Musculoskeletal Tumor Society 2012 대한골관절종양학회지 Vol.18 No.1

목적: 케모카인 수용체인 CXCR4는 암에서 발현되며 암의 전이에 관여한다고 알려져 있다. 저자들은 통상적인 조직학적으로 고등급인 골육종과 저등급 중심부 골육종에서 CXCR4 발현을 비교하고 CXCR4 발현과 예후 간에 연관성이 있는지 살펴보았다. 대상 및 방법: 총 63명의 골육종 환자에서 CXCR4에 대한 면역조직화학검사를 시행하였고 임상적, 병리학적 인자 및 전체적인 생존율과의 연관성을 살펴보았다. 결과: CXCR4는 통상적인 고등급(조직학적 등급 3 및 4) 골육종의 76.3%에서 발현된 반면 저등급(조직학적 등급 1 및 2) 중심부 골육종의 36%에서 발현되었다. 또한 고등급 골육종의 47.4%에서 미만성으로 발현된 반면 모든 저등급 골육종은 병소에 국한되어 발현되었다. CXCR4 발현은 조직학적 등급과 통계학적으로 유의한 상관관계를 나타내었다(p<0.0001). 전체적인 생존률은 CXCR4 발현 증가(p=0.0058), 고등급의 조직학적 등급(p<0.0001), 어린 연령(p=0.0140)에 따라 유의하게 감소하였지만, 성별, 종양 크기, AJCC 병기와는 연관성이 뚜렷하지 않았다. 결론: CXCR4 발현은 골육종에서 고도의 조직학적 분화도가 나쁜 등급 및 불량한 예후와 연관된다. Purpose: The chemokine receptor CXCR4 has been reported to be aberrantly expressed in human cancer and has been shown to participate in cancer metastasis. We compared the expression of CXCR4 in conventional high-grade and low-grade central osteosarcomas, and determined if an association between CXCR4 expression and prognosis could be made. Materials and Methods: We performed the immunohistochemistry for CXCR4 in a total of 63 patients with osteosarcoma and determined the relationships according to the clinicopathologic variables and overall survival rates. Results: CXCR4 was detected in 76.3% of conventional high-grade osteosarcoma patients and in 36% of low-grade central osteosarcomas. Diffuse expression was noted in 47.4% of the high-grade osteosarcomas and all low-grade cases were focal positive. CXCR4 expression was significantly correlated with histologic grade (p<0.0001). While overall survival rate was reduced significantly with increased CXCR4 expression (p=0.0058), higher histologic grade (p<0.0001), and younger age (p=0.0140), survival rate did not correlate with gender, tumor size, or AJCC stage. Conclusion: Our results suggest that CXCR4 expression is associated with higher-grade tumors and with poor prognosis for osteosarcoma patients.