**4.2 Ewing's sarcoma**

Ewing's sarcomas are associated with rearrangement of the *EWS* gene on chromosome 22q12 with an erythroblast transformation-specific (*ETS*) gene family member, resulting in formation of EWS-ETS fusion protein (EWS-FLI). FLI1 has been suggested as a useful marker particularly when hematolymphoid markers are negative. This translocation defines Ewing's sarcoma family of tumors (ESFT) and provides a major tool for their accurate diagnosis. The translocation results in different types of genetic abnormalities, e.g., five forms of EWSR1-FLI1, three forms of EWSR1-ERG, and one form of EWSR1-FEV. A high expression of BMI-1 in ESFT cells was found to significantly affect survival and proliferation. Expression of CXCR4 has been reported to increase the risk of tumor metastases, whereas CXCR7 expression is associated with shorter survival [10].

Ewing's sarcoma has been reported to be associated with modulation of RANKL by VEGF-165, thus resulting in activation of osteoclast-mediated bone destruction [10].

### **4.3 Chondrosarcoma**

On the basis of histological observations, chondrosarcomas are classified into three categories:

Grade I (low grade)—cytology similar to enchondroma and hyperchromatic plump nuclei of uniform size [10].

Grade II (intermediate grade)—increased cellularity, hyperchromasia, distinct nucleoli, and foci of myxoid alteration [10].

Grade III (high grade)—increased cellularity and nuclear atypia, occasional giant cells, abundant necrosis, and presence of mitosis [10].

#### *4.3.1 Genetic markers*

Deletions in the loci of *CDKN2A*, *EXT1*, and *EXT2* genes, *p53* mutation as late event in tumor progression, and amplification of 12q13 and loss of 9p21 are genetic aberrations found in conventional chondrosarcomas [10].

Higher expression of PTHR1 and Bcl-2 was found to be associated with increasing histological grade in chondrosarcoma, suggesting its involvement in tumor progression. A higher expression of Aurora kinases A and B was relevant as prognosis marker for chondrosarcoma. Somatic heterozygous isocitrate dehydrogenase 1 (IDH1) hot spots (R132C and R132H) or IDH2 (R172S) mutations are specifically found in cartilaginous tumors [10].

#### *4.3.2 Biological and molecular markers*

qPCR analysis showed a high expression of COX-2 protein in solitary peripheral chondrosarcoma. Some of the studies reported a significant role of nitrotyrosine, COX-2, CD34, and lymphatic marker podoplanin with histological grades of chondrosarcoma. Molecules such as integrin-linked kinase α and β-parvin and Mig-2 allow attachment of cells to matrix and govern cell motility and growth, thus playing an important role in progression and prognosis of chondrosarcomas [10].

Significantly high serum levels of receptor activator of nuclear factor-κB (RANK), OPG, IL-8, IL-6, and OPG/soluble RANKL ratio have been used to detect bone tumors. Osteosarcoma patients display a higher serum concentration of IL-16 as compared to chondrosarcoma patients [35].

**23**

*Bone Tumors: Types and Treatments*

**5. Diagnosis**

**6. Therapy**

should involve the following:

*DOI: http://dx.doi.org/10.5772/intechopen.86550*

nerves, and soft tissues [1, 12].

1.**Radiographic diagnosis**: Plain radiographs, computed tomography (CT) scans, and magnetic resonance imaging (MRI) are used to investigate the extent of tumors and to study the surrounding structure such as blood vessels,

2.**Positron emission tomography (PET)-CT**: [F-18]-Fluorodeoxy-D-glucose (FDG)-PET is a noninvasive imaging tool used for accurate discrimination

3.**Bone scintigraphy**: This method involves total body scan and identifies axial and appendicular skeletal metastasis. It helps in determining intraosseous

4.**Thallium scintigraphy**: This method is used for determining tumor response to neoadjuvant (preoperative) chemotherapy when MRI is not helpful and also

5.**Incisional or core needle biopsy** is the final step in the diagnostic process. The tumor is staged using the Musculoskeletal Tumor Society staging scheme or

6.**Increased uptake of technetium diphosphonate** in the clinical bone scans of osteolytic lesions in cancer patients also provides a diagnostic tool to identify

Bone scans, X-rays, and histologic evaluation of autopsy specimens are com-

Osteosarcoma is typically treated with surgery and adjuvant chemotherapy that usually includes a combination of methotrexate, doxorubicin, and cisplatin [37]. Once the cancer has spread to the bones, it can rarely be cured, but often it can be treated to slow down its growth [38]. The therapeutic strategies for bone tumors

1.Treatment of cancer cells: This involves inhibition of tumor cell proliferation or killing of cancer cells to extend the patient's survival time. This could be achieved by usage of cytotoxic drugs, hormonal deprivation, or inhibition of

2.Disruption of the vicious cycle created due to complex biological signaling

3.Palliative therapies to reduce the extremely debilitating and painful symptom of bone metastasis and improve the quality of life for cancer patients [4].

As discussed in the previous sections, various signaling pathway are involved in the proliferation and migration of tumor cells. Targeting these signaling pathways by use of different inhibitors could hamper the survival of tumor cells. However, it has

between responding and nonresponding osseous tumors [1, 12].

the American Joint Commission on Cancer (AJCC) system [12].

monly used for radiologic and histologic assessment of tumor sites [5].

extension of tumors and sites of metastasis [1, 12].

increased cellular activity and metastasis [36].

specific signaling pathways by targeted agents [4].

between cancer cells and bone resident cells [4].

for detection of local recurrence [1].
