scholarly journals KPNA2 expression is a potential marker for differential diagnosis between osteosarcomas and other malignant bone tumor mimickers

2020 ◽  
Author(s):  
Lucen Jiang ◽  
Jianghuan Liu ◽  
Qingzhu Wei ◽  
Yiyang Wang
Keyword(s):  
Bone Tumor ◽  
Bone Tumors ◽  
Diagnostic Value ◽  
Benign Tumors ◽  
Malignant Bone Tumor ◽  
Malignant Bone Tumors ◽  
Potential Marker ◽  
Tumors Of Bone ◽  
Bone Sarcomas ◽  
Malignant And Benign Tumors

Abstract Background Karyopherin α 2 (KPNA2), a member of the Karyopherin α family, has been observed in several cancers but lack substantial investigation in malignant bone tumors. The purpose of the current study was to evaluate KPNA2 expression level and its utility as a novel diagnostic biomarker in osteosarcomas and their malignant bone tumor mimickers, such as chondrosarcomas and Ewing sarcomas.Method We investigated the expression of KPNA2 protein by immunohistochemistry on paraffin embedded surgical specimens from 217 patients with malignant and benign tumors of bone, including 81 osteosarcomas, 42 chondrosarcomas, 9 Ewing sarcomas, 28 osteoid osteoma, 20 osteochondroma and 37 Chondroblastoma. Immunoreactivity was scored semi quantitatively based on stain extent and intensity.Results Seventy one of 81 (87.7%) osteosarcomas, zero of 42 (0%) chondrosarcomas and one of 9 (11.1%) Ewing sarcomas showed immunoreactivity for KPNA2. Negative KPNA2 expression was observed in all of benign bone tumors. Much more positive expression of KPNA2 was found in osteosarcomas as compared with chondrosarcomas and Ewing sarcomas. The sensitivity and specificity of KPNA2 immuno-expression for osteosarcoma was 87.7% and 100%, respectively. In several subtypes of osteosarcomas, immunohistochemical expression of KNA2 was more frequent in osteoblastic (94.5%), with 39 (70.9%) showing strong-intensity staining. KPNA2 positivity was observed in eleven of 13 (84.6%) chondroblastic, three of 6 (50%) fibroblastic, three of 4 (75%) telangiectatic and two of 3 (66.7%) giant cell-rich osteosarcoma. Stronger-intensity staining was observed in osteoblastic osteosarcoma.Conclusion KPNA2 is most frequently expressed in osteosarcomas, particularly in osteoblastic and chondroblastic tumors, but is rarely positive in chondrosarcomas and Ewing sarcomas. This feature may have diagnostic value since it is very useful for distinguishing between osteosarcomas and other bone sarcomas mimickers. This report supports KPNA2 as a novel marker for the diagnosis of osteosarcoma.

scholarly journals KPNA2 expression is a potential marker for differential diagnosis between osteosarcomas and other malignant bone tumor mimics

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Lucen Jiang ◽  
Jianghuan Liu ◽  
Qingzhu Wei ◽  
Yiyang Wang
Keyword(s):  
Differential Diagnosis ◽  
Bone Tumor ◽  
Bone Tumors ◽  
Bone Sarcoma ◽  
Malignant Bone Tumor ◽  
Diagnostic Biomarker ◽  
Malignant Bone Tumors ◽  
Benign Bone Tumors ◽  
Potential Marker ◽  
Osteoblastic Osteosarcoma

Abstract Background Karyopherin α2 (KPNA2), a member of the karyopherin α family, has been studied in several cancers but has not yet been substantially investigated in malignant bone tumors. The purpose of the current study was to evaluate the KPNA2 expression level and its utility as a novel diagnostic biomarker in osteosarcomas and malignant bone tumor mimics, such as chondrosarcomas and Ewing sarcomas (ESs). Method We investigated the expression of KPNA2 protein by immunohistochemistry on paraffin-embedded surgical specimens from 223 patients with malignant and benign bone tumors, including 81 osteosarcomas, 42 chondrosarcomas, 15 ESs, 28 osteoid osteomas, 20 osteochondromas and 37 chondroblastomas. Immunoreactivity was scored semiquantitatively based on staining extent and intensity. Results Sixty-seven of 81 (82.7%) osteosarcoma, zero of 42 (0%) chondrosarcoma and one of 15 (6.7%) ES samples showed immunoreactivity for KPNA2. Negative KPNA2 expression was observed in all benign bone tumors. The expression of KPNA2 in osteosarcoma samples was much higher than that in chondrosarcoma and ES samples (P < 0.001). The sensitivity and specificity of KPNA2 immunoexpression for detecting osteosarcoma were 82.7 and 100%, respectively. Several subtypes of osteosarcoma were analyzed, and immunostaining of KPNA2 was frequent in osteoblastic samples (90.9%), with 39 samples (70.9%) showing strong-intensity staining. KPNA2 positivity was observed in ten of 13 (76.9%) chondroblastic, two of 6 (33.3%) fibroblastic, three of 4 (75%) telangiectatic and two of 3 (66.7%) giant cell-rich osteosarcoma samples. The strongest intensity staining was observed in osteoblastic osteosarcoma. Conclusion KPNA2 is frequently expressed in osteosarcomas, particularly in osteoblastic and chondroblastic tumors, but is rarely positive in chondrosarcomas and ESs. This feature may aid in distinguishing between osteosarcoma and other bone sarcoma mimics. This report supports KPNA2 as a novel marker for the diagnosis of osteosarcoma.

scholarly journals KPNA2 expression is a potential marker for differential diagnosis between osteosarcomas and other malignant bone tumor mimics

2020 ◽  
Author(s):  
Lucen Jiang ◽  
Jianghuan Liu ◽  
Qingzhu Wei ◽  
Yiyang Wang
Keyword(s):  
Differential Diagnosis ◽  
Bone Tumor ◽  
Bone Tumors ◽  
Bone Sarcoma ◽  
Malignant Bone Tumor ◽  
Diagnostic Biomarker ◽  
Malignant Bone Tumors ◽  
Benign Bone Tumors ◽  
Potential Marker ◽  
Osteoblastic Osteosarcoma

Abstract Background: Karyopherin α2 (KPNA2), a member of the karyopherin α family, has been studied in several cancers but has not yet been substantially investigated in malignant bone tumors. The purpose of the current study was to evaluate the KPNA2 expression level and its utility as a novel diagnostic biomarker in osteosarcomas and malignant bone tumor mimics, such as chondrosarcomas and Ewing sarcomas (ESs).Method: We investigated the expression of KPNA2 protein by immunohistochemistry on paraffin-embedded surgical specimens from 223 patients with malignant and benign bone tumors, including 81 osteosarcomas, 42 chondrosarcomas, 15 ESs, 28 osteoid osteomas, 20 osteochondromas and 37 chondroblastomas. Immunoreactivity was scored semiquantitatively based on staining extent and intensity.Results: Sixty-seven of 81 (82.7%) osteosarcoma, zero of 42 (0%) chondrosarcoma and one of 15 (6.7%) ES samples showed immunoreactivity for KPNA2. Negative KPNA2 expression was observed in all benign bone tumors. The expression of KPNA2 in osteosarcoma samples was much higher than that in chondrosarcoma and ES samples (P<0.001). The sensitivity and specificity of KPNA2 immunoexpression for detecting osteosarcoma were 82.7% and 100%, respectively. Several subtypes of osteosarcoma were analyzed, and immunostaining of KPNA2 was frequent in osteoblastic samples (90.9%), with 39 samples (70.9%) showing strong-intensity staining. KPNA2 positivity was observed in ten of 13 (76.9%) chondroblastic, two of 6 (33.3%) fibroblastic, three of 4 (75%) telangiectatic and two of 3 (66.7%) giant cell-rich osteosarcoma samples. The strongest intensity staining was observed in osteoblastic osteosarcoma.Conclusion: KPNA2 is frequently expressed in osteosarcomas, particularly in osteoblastic and chondroblastic tumors, but is rarely positive in chondrosarcomas and ESs. This feature may aid in distinguishing between osteosarcoma and other bone sarcoma mimics. This report supports KPNA2 as a novel marker for the diagnosis of osteosarcoma.

Association of The Cytotoxic T Lymphocyte Antigen-4 +49G/A Gene Polymorphism with Susceptibility to Malignant Bone Tumors

2020 ◽  
Author(s):  
Ningfeng Guo ◽  
Yaojun Wu ◽  
Yueming Hu
Keyword(s):  
T Lymphocyte ◽  
Bone Tumor ◽  
Bone Tumors ◽  
Cytotoxic T Lymphocyte ◽  
Meta Analysis ◽  
Population Based ◽  
Cochrane Library ◽  
Malignant Bone Tumor ◽  
Malignant Bone Tumors ◽  
Lymphocyte Antigen

Abstract Background Earlier research works have studied the part that cytotoxic T-lymphocyte antigen-4 (CTLA-4) plays in the carcinogenesis of malignant bone tumors, nonetheless, findings had inconsistency. The current investigation aims at clarifying the association between CTLA-4 polymorphism and malignant bone tumor susceptibility through the meta-analysis.Methods We searched pertinent research works in not just PubMed, but also EMBASE, Cochrane library, and Chinese National Knowledge Infrastructure (CNKI) databases in humans published before October 2019. The use of the pooled odds ratio (OR) with its 95% confidence interval (95%CI) was made for estimating the strengths of the correlation existing between the CTLA-4 genetic polymorphism and malignant bone tumors susceptibility. An aggregate of six research works with 1191 malignant bone tumors patients and 1418 controls were selected eventually. The pooled results shed light on the fact that CTLA-4 +49G/A polymorphism had a significant correlation with an augmented vulnerability to the malignant bone tumors (A vs. G: OR=1.37, 95%CI=1.22-1.54; GA vs. GG: OR=1.20, 95%CI=1.01-1.42; AA vs. GG: OR=2.13, 95%CI=1.63-2.78; GA+AA vs. GG: OR=1.35, 95%CI=1.15-1.59; AA vs. GG+GA: OR=2.02, 95%CI=1.60-2.56). Subgroup analysis indicated that there exists a statistically significant correlation between CTLA-4 +49G/A polymorphism and augmented susceptibility to the malignant bone tumor in the population-based or hospital-based samples, and Ewing’s sarcoma or osteosarcoma. Moreover, there was also not observed any considerable heterogeneity across the research works. Results Our results suggest that the CTLA-4 +49G/A polymorphism may play a pivotal part in the carcinogenesis of malignant bone tumors. Conclusions More research works, on the basis of the large sample sizes as well as homogeneous specimens, are needed in order to verify these results.

Orthotopic murine model of a primary malignant bone tumor in the spine: functional, bioluminescence, and histological correlations

2014 ◽  
Vol 21 (3) ◽  
pp. 378-385
Author(s):  
Daniel K. Fahim ◽  
Claudio E. Tatsui ◽  
Dima Suki ◽  
Joy Gumin ◽  
Frederick F. Lang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Bone Tumor ◽  
Murine Model ◽  
Bone Tumors ◽  
Time Course ◽  
Spinal Metastasis ◽  
Malignant Bone Tumor ◽  
Orthotopic Model ◽  
Malignant Bone Tumors ◽  
Primary Malignant Bone Tumor

Object There is currently no reproducible animal model of human primary malignant bone tumors in the spine to permit laboratory investigation of the human disease. Therefore, the authors sought to adapt their previously developed orthotopic model of spinal metastasis to a model for primary malignant bone tumors of the spine. Methods A transperitoneal surgical approach was used to implant osteosarcoma (Krib-1) into the L-3 vertebral body of nude mice via a drill hole. Motor function was evaluated daily using the previously validated qualitative key milestones of tail dragging, dorsal stepping, hindlimb sweeping, and paralysis. A subset of these animals was euthanized upon reaching the various milestones, and the spines were removed, sectioned, and stained. The degree of spinal cord compression was correlated with the occurrence of milestones and assessed by a ratio between the neural elements divided by the area of the spinal canal. Another subset of animals received stably transfected Krib-1 cells with the luciferase gene, and bioluminescence was measured at 10, 20, and 30 days postimplantation. Results Osteosarcoma xenografts grew in all animals according to a reliable and reproducible time course; the mean time for development of behavioral milestones was noted in relation to the day of implantation (Day 1). Tail dragging (Milestone 1) occurred on Day 19.06 (95% CI 16.11–22.01), dorsal stepping (Milestone 2) occurred on Day 28.78 (95% CI 26.79–30.77), hindlimb sweeping (Milestone 3) occurred on Day 35.61 (95% CI 32.9–38.32), and paralysis of the hindlimb (Milestone 4) occurred on Day 41.78 (95% CI 39.31–44.25). These clinically observed milestones correlated with increasing compression of the spinal cord on histological sections. The authors observed a progressive increase in the local bioluminescence (in photons/cm2/sec) of the implanted level over time with a mean of 2.17 (range 0.0–8.61) at Day 10, mean 4.68 (range 1.17–8.52) at Day 20, and mean 5.54 (range 1.22–9.99) at Day 30. Conclusions The authors have developed the first orthotopic murine model of a primary malignant bone tumor in the spine, in which neurological decline reproducibly correlates with tumor progression as evidenced by pathological confirmation and noninvasive bioluminescence measurements. Although developed for osteosarcoma, this model can be expanded to study other types of primary malignant bone tumors in the spine. This model will potentially allow animal testing of targeted therapies against specific primary malignant tumor types.

scholarly journals Modern Methods of Visualization in Diagnosis, Staging and Elaboration of Treatment Tactics for Primary Malignant Bone Tumors. Part I

2016 ◽  
Vol 23 (3) ◽  
pp. 53-62
Author(s):  
G. N Machak ◽  
A. K Morozov ◽  
A. I Snetkov ◽  
I. N Karpov ◽  
N. V Kochergina ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Bone Tumors ◽  
Diagnostic Techniques ◽  
Disease Stage ◽  
Malignant Bone Tumors ◽  
Modern Methods ◽  
Bone Sarcomas ◽  
High Degree ◽  
Modern Technologies

At present the oncologists have great potentialities in diagnostic techniques that enable to determine not only the structural but functional characteristics of the tumor as well. The use of modern technologies of medical visualization for diagnosis, determination of the disease stage and effectiveness of neoadjuvant chemotherapy in patients with bone sarcomas of high degree (G3-G4) malignancy is presented.

scholarly journals Modern Methods of Visualization in Diagnosis, Staging and Elaboration of Treatment Tactics for Primary Malignant Bone Tumors. Part I

2016 ◽  
pp. 53-62
Author(s):  
G. N. Machak ◽  
A. K. Morozov ◽  
A. I. Snetkov ◽  
I. N. Karpov ◽  
N. V. Kochergina ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Bone Tumors ◽  
Diagnostic Techniques ◽  
Disease Stage ◽  
Malignant Bone Tumors ◽  
Modern Methods ◽  
Bone Sarcomas ◽  
High Degree ◽  
Modern Technologies

At present the oncologists have great potentialities in diagnostic techniques that enable to determine not only the structural but functional characteristics of the tumor as well. The use of modern technologies of medical visualization for diagnosis, determination of the disease stage and effectiveness of neoadjuvant chemotherapy in patients with bone sarcomas of high degree (G3-G4) malignancy is presented.

scholarly journals Diffusion-weighted Magnetic Resonance Imaging in the Diagnosis of Bone Tumors: Preliminary Results

2013 ◽  
Vol 3 ◽  
pp. 63 ◽  
Author(s):  
Yeliz Pekcevik ◽  
Mehmet Onur Kahya ◽  
Ahmet Kaya
Keyword(s):  
Magnetic Resonance ◽  
Bone Tumors ◽  
Malignant Tumors ◽  
Receiver Operating Curve ◽  
Benign Tumors ◽  
Single Shot ◽  
Malignant Bone Tumors ◽  
Diffusion Weighted ◽  
Adc Values ◽  
The Mean

Objective: The study aims to determine whether apparent diffusion coefficient (ADC) can help differentiate benign and malignant bone tumors. Materials and Methods: From January 2012 to February 2013, we prospectively included 26 patients. Of these 15 patients were male and 11 were female; ranging in age from 8 to 76 years (mean age, 34.5 years). Diffusion-weighted magnetic resonance (MR) imaging was obtained with a single-shot echo-planar imaging sequence using a 1.5T MR scanner. We grouped malignant lesions as primary, secondary, and primary tumor with chondroid matrix. The minimum ADC was measured in the tumors and mean minimum ADC values were selected for statistical analysis. ADC values were compared between malignant and benign tumors using the Mann-Whitney U-test and receiver operating curve analysis were done to determine optimal cut-off values. Results: The mean ADC values from the area with lowest ADC values of benign and malignant tumors were 1.99 ± 0.57 × 10−3 mm2/s and 1.02 ± 1.0 × 10−3 mm2/s, respectively. The mean minimum ADC values of benign and malignant tumors were statistically different (P = 0.029). With cut-off value of 1.37 (10−3 mm2/s), sensitivity was 77.8% and specificity was 82.4%, for distinguishing benign and malignant lesion. Benign and secondary malignant tumors showed statistically significant difference (P = 0.002). There was some overlap in ADC values between benign and malignant tumors. The mean minimum ADC values of benign and malignant chondroid tumors were high. Giant cell tumor, non-ossifying fibroma and fibrous dysplasia showed lower ADC values. Conclusion: Although there is some overlap, ADC values of benign and malignant bone tumors seem to be different. Further studies with larger patient groups are needed to find an optimal cut-off ADC value.

scholarly journals Femoral Expandable Prosthesis In Bone Tumor of an Adult: A Case Report

Folia Medica ◽  
2018 ◽  
Vol 60 (3) ◽  
pp. 483-489
Author(s):  
Domenico Fenga ◽  
Michele A. Rosa
Keyword(s):  
Bone Tumor ◽  
Bone Tumors ◽  
New Technologies ◽  
Adult Population ◽  
Lower Limbs ◽  
Review Of Literature ◽  
Leg Length ◽  
Endoprosthetic Replacement ◽  
Malignant Bone Tumors ◽  
Point Of Interest

Abstract Management of bone tumors of the limbs is still a field to be explored. The problems to be faced are diff erent, especially when the lower limbs are the point of interest, due to the diff erent leg length residual. A possible solution, provided by new technologies, is the use of electromagnetic expandable prosthesis. This device is successfully used in the management of paediatric malignant bone tumors. The strength of this prosthesis is the possibility to assist the musculoskeletal growth in children. To our acknowledge review of literature points out only few cases in which this mechanism is used in adult population. The authors present their results with expandable endoprosthetic replacement in an adult patient with severe lower limb discrepancy which occurred after a malignant bone tumor of the knee, obtaining a recovery of approximately 6 cm.

scholarly journals Diagnostic value of Thallium-201 scintigraphy in differentiating malignant bone tumors from benign bone lesions

2015 ◽  
Vol 29 (8) ◽  
pp. 674-681 ◽  
Author(s):  
Ryota Inai ◽  
Takayoshi Shinya ◽  
Akihiro Tada ◽  
Shuhei Sato ◽  
Tomohiro Fujiwara ◽  
...  
Keyword(s):  
Bone Tumors ◽  
Diagnostic Value ◽  
Thallium 201 ◽  
Bone Lesions ◽  
Malignant Bone Tumors ◽  
Thallium 201 Scintigraphy

scholarly journals A narrative review on the characteristics and treatment of benign and malignant bone tumors

2020 ◽  
Vol 37 (4) ◽  
pp. 325-336
Author(s):  
Frydoni Bahrami ◽  
Esmaeilnejad-Ganji Mokhtar
Keyword(s):  
Bone Tumor ◽  
Bone Tumors ◽  
Distal Femur ◽  
Proximal Tibia ◽  
Health Workers ◽  
The Body ◽  
Malignant Bone Tumors ◽  
Benign Bone Tumors ◽  
Malignant Lesions ◽  
Cartilaginous Tumors

Bone tumors, including benign and malignant lesions, are not metastatic; however, they may appear in any part of the body skeleton. Distal femur and proximal tibia (around the knee joint) are the most prevalent sites. Most benign bone tumors are cartilaginous tumors, known as osteochondromas. Based on the reports, benign bone tumors are more frequent than primary malignant ones. Malignant bone tumor is another type of bone tumor, which usually occurs within the first years of life. As a result, it can considerably affect the lives of patients and their families. These tumors consist of osteosarcoma, chondrosarcoma, and Ewing's sarcoma. This article discusses the epidemiology, characteristics, and treatment of the most important types of benign and malignant bone tumors. These data will be useful to the physicians and other health workers to better understand the conditions of bone tumors and their management.

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