**5. Diagnosis**

*Hormone Therapy and Replacement in Cancer and Aging-Related Diseases*

expression is associated with shorter survival [10].

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

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

On the basis of histological observations, chondrosarcomas are classified into

Grade I (low grade)—cytology similar to enchondroma and hyperchromatic

Grade III (high grade)—increased cellularity and nuclear atypia, occasional

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

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

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

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

Grade II (intermediate grade)—increased cellularity, hyperchromasia, distinct

**4.2 Ewing's sarcoma**

destruction [10].

three categories:

*4.3.1 Genetic markers*

**4.3 Chondrosarcoma**

plump nuclei of uniform size [10].

found in cartilaginous tumors [10].

*4.3.2 Biological and molecular markers*

as compared to chondrosarcoma patients [35].

chondrosarcomas [10].

nucleoli, and foci of myxoid alteration [10].

giant cells, abundant necrosis, and presence of mitosis [10].

aberrations found in conventional chondrosarcomas [10].

**22**


Bone scans, X-rays, and histologic evaluation of autopsy specimens are commonly used for radiologic and histologic assessment of tumor sites [5].
