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

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.

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Lucen Jiang ◽  
Jianghuan Liu ◽  
Qingzhu Wei ◽  
Yiyang Wang

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.


2020 ◽  
Author(s):  
Lucen Jiang ◽  
Jianghuan Liu ◽  
Qingzhu Wei ◽  
Yiyang Wang

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.


2020 ◽  
Author(s):  
Ningfeng Guo ◽  
Yaojun Wu ◽  
Yueming Hu

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.


2020 ◽  
Vol 37 (4) ◽  
pp. 325-336
Author(s):  
Frydoni Bahrami ◽  
Esmaeilnejad-Ganji Mokhtar

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.


2014 ◽  
Vol 21 (3) ◽  
pp. 378-385
Author(s):  
Daniel K. Fahim ◽  
Claudio E. Tatsui ◽  
Dima Suki ◽  
Joy Gumin ◽  
Frederick F. Lang ◽  
...  

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.


2010 ◽  
Vol 134 (10) ◽  
pp. 1460-1466 ◽  
Author(s):  
David R. Lucas

Abstract Osteoblastoma is a rare benign bone tumor. Although the histologic features in most cases are distinctive, there are various permutations that make the diagnosis challenging. It can mimic a variety of other benign bone tumors, but more importantly, distinguishing it from osteoblastoma-like osteosarcoma can be difficult. In this case report, I describe the clinicopathologic findings for a 13-year-old adolescent boy with T7 spinal osteoblastoma and review salient clinical, radiographic, and pathologic features of osteoblastoma, as well as the differential diagnoses.


Folia Medica ◽  
2018 ◽  
Vol 60 (3) ◽  
pp. 483-489
Author(s):  
Domenico Fenga ◽  
Michele A. Rosa

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.


2016 ◽  
Vol 106 (3) ◽  
pp. 225-228 ◽  
Author(s):  
Ersin Ercin ◽  
Mustafa Gokhan Bilgili ◽  
Mehmet Gamsizkan ◽  
Serdar Avsar

Osteochondromas are the most common benign bone tumors. They are usually asymptomatic and found incidentally. When symptomatic, the symptoms are usually due to its location and size. Fracture of an osteochondroma presenting as posterior ankle impingement is a rare condition. We describe a 22-year-old man with solitary exostosis who presented with a posterior ankle mass and posterior ankle impingement with 2 years of follow-up. Surgical intervention was the treatment of choice in this patient, and histologic examination revealed a benign osteochondroma. Osteochondromas found in the posterior aspect of the talus can be complicated by fracture due to persistent motion of the ankle. Talar osteochondroma should be included in the differential diagnosis of posterior ankle impingement causes. Posterior talar osteochondromas, especially when a stalk is present, should be treated surgically before it is more complicated by a fracture and posterior ankle impingement.


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