What is the difference between osteosarcoma and chondrosarcoma

This is continued unless there is a change in clinical examination findings or the radiographic appearance of the lesion at different points in time.

Symptomatic enchondromas i. Fractures through the tumor called a pathologic fracture can be treated with either concurrent or staged treatment of both the fracture and the lesion if there is concern over the risk of recurrent pathologic fracture.

Surgical resection remains the primary and most successful means of treating chondrosarcomas. The decision regarding the extent of surgical resection and adjuvant therapy is dependent upon the clinical and histologic characteristics of the lesion. Optimal treatment for low-grade chondrosarcoma remains a dilemma for surgical oncologists, but no chemotherapy or radiation is indicated. For higher-grade tumors, with a worse prognosis for recurrence and metastasis, adjuvant therapies may be considered.

Unfortunately, to date, studies have not shown adjuvant treatments such as chemotherapy or radiation to have any significant impact on patient morbidity or mortality in the majority of isolated primary lesions. Proton beam radiation is generally reserved for refractory tumors in high risk anatomic areas such as the skull base and axial skeleton. As these adjunctive modalities are of no proven benefit, the burden of a cure still falls upon adequate initial surgical resection.

Irradiation may be useful in younger patients or those with metastatic disease, where surgery would cause major unacceptable morbidity or be technically impossible Krochak et al.

This remains controversial. Cytotoxic chemotherapy is ineffective against traditional chondrosarcomas, but may have a role in the dedifferentiated subtype or in stage IV disease Dickey et al. There are no established regiments for such cases. For patients who have developed pulmonary metastatic disease, treatment in a clinical trial at a Sarcoma Center , or with conventional chemotherapy, if appropriate for the patient, may be indicated.

In the past, wide resection was considered the method of choice for all chondrosarcomas. Unfortunately, these tumors are frequently found in regions such as the pelvis or proximal long bones, where aggressive surgical management may endanger adjacent vital organs and structures or compromise limb function. Thus, less aggressive approaches such as marginal excision and extended intralesional excision with margin expansion using adjuncts such as phenol or cryotherapy have received increasing attention with a national study underway to investigate efficacy.

Most surgical oncologists prefer limb salvage techniques with bone graft and prosthetics, preserving the function of the limb. Amputation is still used in advanced disease or as a last option. While rigorous evidence-based criteria are presently lacking, individual centers may have their own criteria and algorithms for surgical decision-making. In general, benign lesions should be treated conservatively, while high-grade malignancies should be treated aggressively with complete resection.

During the past several years, substantial new insights have been gained about molecular cell biology, molecular cytogenetics, and immunopathology Terek, These have led to a better understanding of chondrosarcoma development at the molecular level and will ultimately lead to the development of targeted treatments.

Though they are at present highly experimental, researchers are investigating several new treatments for chondrosarcoma. Examples include agents targeting estrogen receptors Cleton-Jansen et al. Patients with chondrosarcoma are best treated at major Sarcoma Centers with specialized diagnostic and treatment facilities and the availability of musculoskeletal tumor specialists or orthopedic oncologists.

Because this disease, like all bone sarcomas, are not common, it is often a good idea to seek an opinion from a major cancer center that has a wide experience in treating bone cancers.

A Sarcoma Center will offer an organized group of doctors and other health care professionals who work together to provide the best treatment options and recovery. If your primary care physician suspects chondrosarcoma, a simple referral to an orthopedic doctor may not be adequate. Be sure that you are referred to an orthopaedic oncologist or "bone cancer specialist.

In general, the prognosis for chondrosarcoma depends on the grade of the tumor and the attainment of complete excision of the tumor and other conditions the patient has such as diabetes, lupus, and clotting and coagulation problems Table 2. For lower grade chondrosarcomas, prognosis is very good after adequate excision.

There is a low incidence of pulmonary metastasis if the primary lesion is widely resected. Metastasis to other bones can occur, but is much less common. Dedifferentiated chondrosarcoma have a uniformly poor prognosis. Cartilaginous lesions of the human skeleton exist on a continuum spanning from the completely benign embryonic inclusion, to the dangerously aggressive neoplastic process.

In order to determine the appropriate treatment for each individual lesion, musculoskeletal oncologists must take into account the clinical, radiographic, histologic and soon the microbiologic characteristics of the tumor.

It is important for patients to seek treatment for these tumors at a Sarcoma center with availability of specialists possessing a sound understanding of these lesions and a firm grasp of the evolving treatment options. The health care team at these centers will keep patients informed about the details of the treatment course in both the short and long term. Understanding and recognizing the spectrum of appearances of the various types of chondrosarcoma allow improved patient assessment and are vital for optimal clinical management including diagnosis, biopsy, staging, treatment and prognosis.

As more advanced molecular tools for predicting tumor behavior are developed, more sophisticated means of diagnosing and treating these tumors will be developed and put into use. A Note from Dr. Letson, Coordinating Editor : One of the most controversial subjects in musculoskeletal tumor surgery is how to manage low-grade chondrosarcomas.

It is the grading of this disease that makes it so challenging, and the final diagnosis is dependent on clinical, radiologic and pathologic findings. These concepts have been well-presented here in this extended Op Ed piece by Drs.

Novais and Randall. Chondrosarcoma is a rare disease, with an estimated incidence of 1 in , per year. The age distribution of patients with chondrosarcoma shows a gradual age-related increase, with the peak incidence occurring during the sixth and seventh decades of life. Chondrosarcomas are actually a heterogeneous group of tumors. They are classified as primary or conventional chondrosarcoma if they are unassociated with a pre-existing lesion and secondary if they develop from a pre-existing chondroid lesion, such as enchondroma or osteochondroma.

They can be further sub classified as central when they arise from within the medullary cavity and peripheral when they arise from the surface of the bone. Conventional chondrosarcoma are nearly always central; secondary chondrosarcomas can be central but usually they are peripheral. They can also be classified by their location within the body i. The single most important factor to consider when evaluating the malignant potential of a chondrosarcoma is its cytologic and histologic grade, determined by the appearance of tumor material under the microscope combined with the clinical and radiologic presentation Table 1.

While grading is very important in the management of chondrosarcoma, it can be contentious. Although several grading systems have been described, usually they are graded on a scale of The grading is based primarily on nuclear size of tumor cells, nuclear staining hyperchromasia, or darker staining of nuclear material and cellularity. Please see Sandberg and Bridge , 12 Sandberg , and Bovee et al. An enchondroma is a benign bone tumor. Low grade chondrosarcoma also has relatively little potential to spread but can recur locally if not treated appropriately.

If these tumors due recur they can start to behave more aggressively. Distinguishing chondrosarcoma from its benign counterpart, enchondroma, is crucial to the patient treatment and prognosis but can be difficult at times. The diagnosis of cartilage lesions requires expert evaluation. First, clinical and radiographic features such as the age of the patient, symptoms, localization in the skeleton, and the pattern of bone destruction or mineralization should be scrutinized.

The role of biopsy in low grade lesions is quite contentious as sampling errors are a distinct possibility. A wait and see approach is generally recommended at first. If symptoms worsen or there is a progression on radiographic examination then consideration for intralesional surgical treatment may be indicated.

Because of the possibility that the tumor is a low grade chondrosarcoma, it should be removed by an experienced musculoskeletal oncologist at a designated sarcoma center with expert pathology and radiology support. The removed specimen must be thoroughly evaluated for features concerning for malignancy.

Patients with chondrosarcoma experience a wide range of clinical courses, from slow insidious tumor growth over years in low grade lesions to rapid neoplastic progression, metastasis, and death in higher grade lesions.

The vast majority of chondrosarcomas is low grade and accordingly is very slow to progress. Clinical symptoms may be helpful in the initial evaluation of a cartilaginous tumor. Pain is more common with chondrosarcoma than with the benign enchondroma.

Radiographs - Enchondromas and low grade intramedullary chondrosarcomas of long bones can have similar radiologic appearances. Both types of tumors demonstrate stippled calcifications, and both may display endosteal scalloping on plain radiographs.

The margins of the tumor should be examined for osteolysis and endosteal scalloping. Chondrosarcoma can demonstrate adaptive and aggressive radiologic signs.

Cortical expansion and thickening are adaptive changes, and cortical disruption and soft-tissue masses are aggressive changes associated with chondrosarcoma. The extent and degree of endosteal scalloping correlate with the likelihood of the lesion being a chondrosarcoma. The imaging characteristics that should suggest chondrosarcoma are endosteal scalloping depth and extent greater than two-thirds of cortical thickness and along more than two thirds of the lesion , extent of matrix mineralization within less than two-thirds of the lesion as seen on radiographs , presence of cortical remodeling or destruction and thickening, periosteal reaction, pathologic fracture, and associated soft-tissue mass.

Anatomic tumor localization is different but should not be considered of diagnostic value. Enchondromas are most common in the hands or feet while chondrosarcomas are common in the axial skeleton spine and pelvis , typically with large associated soft-tissue masses. The ilium is the most frequently involved bone followed by the proximal femur, proximal humerus, distal femur and ribs. Enchondromas as a rule should not progress during adulthood and any change in size or radiographic appearance of an enchondroma should be considered as a red flag for the presence of a malignant tumor.

CT is superior to radiography for detecting focal areas of scalloping and is considered the best modality to detect mineralization characteristic of a chondroid neoplasm. The axial and coronal images accurately demonstrate marrow replacement by tumor, providing measurements that can guide the surgeon when either an intralesional or a wide excision is performed.

The relationship of a soft-tissue mass to important paraosseous structures, such as the joint capsule and the neurovascular bundle, is accurately demonstrated on MR images. Fast contrast-enhanced MR imaging has the potential to help differentiation between enchondroma and chondrosarcoma. MR imaging results should be seen as an additive tool and may not be considered alone. The use of gadolinium-enhanced MR imaging adds substantially to the characterization of cartilaginous tumors.

The timing and progression of gadolinium contrast enhancement patterns may help direct a clinician toward or away from a diagnosis of malignancy. This feature is usually absent in benign cartilaginous lesions. Bone Scan - This test works by injecting a small amount of radioactive material into the blood stream and taking images using a gamma camera to detect uptake of radioactive material.

Bone scintigraphy has limited application in the differential diagnosis of tumors with low biologic activity such as Grade-I chondrosarcoma. A whole-body bone scan with a high degree of radionuclide uptake within the lesion compared with an internal standard, such as the anterior superior iliac spine or acromioclavicular joint, has been considered as more consistent with chondrosarcoma than enchondroma 17 Figure 3. PET Scan - Recently, there has been some research into the use of a specialized radiographic test called fluorine fluorodeoxyglucose positron emission tomography FDG PET for grading of tumors in patients with chondrosarcoma Preliminary studies showed that FDG PET could be an objective and quantitative adjunct in differentiating chondrosarcomas from enchondromas and osteochondromas and in assessing the grade of chondrosarcomas.

It is important to understand the advantages and disadvantages of imaging modalities for accurate interpretation of results. Although positron emission tomography has limitations, it may be useful for predicting high-grade chondrosarcomas from benign chondroid lesions and grade-I chondrosarcoma.

After all of the imaging modalities are obtained an experienced orthopaedic oncologist must decide whether to observe the patient or intervene. If a low grade chondrosarcoma is suspected, then an aggressive curettage is indicated.

When a more aggressive lesion is suspected a sampling biopsy is indicated as surgical excision is more extensive and so the diagnosis of a high grade cancer should be established. When fresh tissue from a chondrosarcomas is viewed under a microscope after a biopsy, lower grade chondrosarcomas will exhibit increasing amounts of relatively acellular cartilage stroma as well as regions of modestly increased cellularity.

By contrast, higher-grade lesions tend to harbor regions of densely packed hyperchromatic malignant looking cells. Histologic features to distinguish benign from malignant cartilaginous tumors were advocated in the past although the diagnostic value of individual morphologic criteria or how they are handled in clinical practice is controversial.

In that study there was considerable interobserver variability, even among expert bone tumor pathologists, in the histologic diagnosis of enchondroma and low-grade chondrosarcoma. In an attempt to distinguish between low-grade chondrosarcoma and enchondroma the authors identified four most important histologic parameters, as following: host bone entrapment, high cellularity, marked nuclear pleomorphism, and irregular distribution of cells.

The management of low grade chondrosarcoma can be a challenge. Grade I chondrosarcomas may not all behave in the same way clinically or radiographically. In some cases a painful cartilaginous lesion in a long bone has the radiologic appearance of a low-grade chondrosarcoma e.

This borderline type of lesion has been referred as grade 0. The key for long term successful treatment of these lesions is to adequately identify those patients who would benefit from less aggressive surgical resection without the risks of local recurrence and distant metastasis.

The local recurrence rate and potential for metastasis in low-grade chondrosarcoma are low, so limited surgery intralesional resection with adjuvant therapy has been advocated for less aggressive-appearing lesions. In their series, tumors that had no associated cortical perforation or soft tissue mass were successfully treated with intralesional curettage.

Patients with more aggressive lesions eg, cortical disruption, Stage IB were selected for en bloc resection and had excellent local control. They excluded lesions of the central skeleton because these historically behave differently from long bone lesions.

Marco et al described a subset of patients with low-grade chondrosarcoma that could be treated with intralesional excision with adjuvant therapy without compromise of the oncologic outcome: painful, intramedullary low-grade chondrosarcoma stage IA of the appendicular skeleton, which can demonstrate a high degree of endosteal scalloping without adaptive or aggressive radiologic signs.

The only local recurrence in their series was in a patient with cortical disruption and expansion, as well as a soft tissue mass.

Bauer 5 reported on patients with low-grade intramedullary chondrosarcoma of a long bone treated by intralesional excision and followed for years. The authors concluded that a central grade I chondrosarcoma of long bones can be treated with curettage and filling with either bone graft or bone cement methylmethacrylate but distal more radiographic aggressive lesions requires en bloc resection.

Lesions of the pelvis and shoulder girdle should also be treated aggressively since they have a high risk of recurrence. In another recent study Van Der Geest et al 29 reported excellent oncological and functional results the use of cryosurgery as an adjuvant in the surgical treatment of active or aggressive enchondromas and chondrosarcomas grade I. Post-operative fracture was seen as the most common complication in their series. Most authors agree that adequate surgical margins lower the risk of local recurrence in patients with chondrosarcoma.

Wide resection is recommended for virtually all low grade chondrosarcomas of the pelvis and sacrum because in these locations there is a higher chance of local recurrence and metastasis. Adjuvant radiation and chemotherapy have been reserved for patients who have a mesenchymal chondrosarcoma or a dedifferentiated chondrosarcoma or for those who have had inadequate operative treatment.

There is no indication for the use of chemotherapy or radiation in the management of low grade chondrosarcoma as adequate initial surgical resection can virtually be successful in all patients.

Earlier this decade, a national clinical trial was opened in the United States. Investigators hope that the trial can be reinitiated soon. During the past several years, substantial new insights have been gained about molecular cell biology, molecular cytogenetics, and immunopathology. Examples include agents targeting estrogen receptors, 35 new chemotherapeutic agents, such as ET, 36 and agents effecting cytogenetic pathways.

Patients with chondrosarcoma are best treated at major Sarcoma centers with specialized diagnostic and treatment facilities and the availability of Musculoskeletal Tumor Specialists or Orthopedic Oncologists.

Because this, like many other bone cancers, are not common, it is often a good idea to seek an opinion from a major cancer center that has a wide experience in treating bone cancers. A major sarcoma center will offer an organized group of doctors and other health care professionals who work together to provide the best treatment options and recovery. In general, the prognosis for chondrosarcoma depends on the grade of the tumor and the attainment of complete excision of the tumor and other conditions the patient has such as diabetes, lupus, and clotting and coagulation problems.

Table 2 below shows a comparison between the prognosis based on the tumor grade. Pathological fracture, metastasis, local recurrence, and death are usually more common in patients with a high grade chondrosarcoma. For low grade chondrosarcomas, prognosis is excellent after adequate excision, with very low rates of recurrence or spread when treated at an established sarcoma center.

In a review of 70 patients with low grade chondrosarcoma of the appendicular skeleton only three presented with metastasis. Cartilaginous lesions of the human skeleton exist on a continuum, spanning from the completely benign embryonic inclusion, to the far less common but dangerously aggressive neoplastic process. Differentiating a benign enchondroma lesion from a low grade grade I chondrosarcoma is a challenging task even for the more experienced team of Sarcoma specialists.

Based upon imaging characteristics, for less aggressive lesions, a wait and watch approach is the best initial management. At follow-up, if there appears to be progression, intervention should be considered. The majority of patients with less radiographically aggressive low grade chondrosarcoma may be safely treated with a limited surgical interventional intralesional resection. Patients with any signs of a radiographically aggressive lesion should be treated with a staged biopsy and a more extensive wide resection surgery to keep the local recurrence rate and potential for metastases low.

In order to determine the appropriate treatment for each individual lesion, musculoskeletal oncologists must take into account the clinical, radiographic, histologic and soon the molecular biologic characteristics of the tumor. It is important for patients to seek treatment for these tumors at a recognized sarcoma center with availability of specialists possessing a sound understanding of these lesions and a firm grasp of the evolving treatment options.

In April , after finishing up an 8th month yoga teacher training program, I saw an orthopedic doctor about a lump on my outer left thigh that had started to cause pain above my knee. The doctor told me I had a tumor and needed to see a specialist in orthopedic oncology. A few weeks later I had scans and an open biopsy at Memorial Sloan Kettering. The tumor had also bowed my femur.

She reported that there were as many opinions on the best course of treatment as there were doctors in the room. Eventually I was given a list of seven options for surgery, and the choice felt impossible. Read more. My family and I are from British Columbia, Canada. Craft AW Controversies in the management of bone tumours. Cancer Surveys 3: — Google Scholar.

J Clin Oncol 2: — Google Scholar. In: Van Unnik ed The management of bone and soft tissue sarcomas. Raven, New York in press Google Scholar. A review of one hundred and forty-five operative cases. Cancer Treat Rep — Google Scholar. A model for adjuvant chemotherapy and the rationale for the time of thoracic surgery.

Cancer — Google Scholar. Kotz R Possibilities and limitations of limb- preserving therapy for bone tumors today. Neoplastic bone disease includes metastatic lesions and primary bone neoplasms. We divide primary bone neoplasms into two groups: benign and malignant bone neoplasms. Primary malignant bone neoplasms are quite rare and account for 0. According to the SEER registry, from to , on average, the diagnosis of cancer is made around 41 years. Approximately, Annually, the incidence rate was 0.

In the US, the median age at death for bone cancer is 58 years. The mortality for year is 0. The etiology of malignant bone cancers is largely unknown. Some precancerous conditions, e.

The clinical presentation of bone tumors is non-specific. Pain, swelling and general discomfort are the most common symptoms. Pathologic fractures are often tardive manifestations of the disease. Other clinical features include: limitation of movement, hyperthermia of the skin, loss of weight and alteration of anatomic profile with a visible mass Singer and David, ; Jawad and Scully, ; Szuhai et al.

The diagnosis of bone neoplasms is histological, through a biopsy. Clinical and radiological features are important to integrate diagnostic algorithms and to complete the staging of bone cancer.

Tumor staging, for prognostic purposes, includes the degree of differentiation and the local and distant diffusion. The biological classification allows to evaluate the behavior of the malignant lesion. There are different grading systems with two TNM two grade system , three or four grades. The higher the grade, the more aggressive is the cancer.

The classification of sarcomas is based on criteria of Broders for grading squamous cell carcinoma Fletcher et al. In order to stage a neoplasm, we consider the grading together with other parameters such as local extension, and lymphonodal and distant metastasis. There are different staging systems based on clinical, radiological and histological features. The TNM staging system is also valid for bone neoplasm, but is not commonly used because sarcomas do not usually metastasize to lymph nodes.

The Enneking surgical staging system for malignant mesenchymal tumors takes into account the surgical grade G, G1, G2 , local extent T, T1, T2 , and presence or absence of metastasis M0, M1. The staging system for malignant musculoskeletal sarcomas consists of three stages.

Stage III represents any tumor with distant metastasis. Stages I and II are based on surgical grade of the tumor. Each stage is further divided into two subcategories A, B based on the local extent of the tumor. This last parameter, i. While the role of radiology and histology in the diagnosis, prognosis and treatment of bone neoplasm has been well-defined for several years, the role of biochemical markers serum, genetic or histological markers is still unclear. The purpose of this review is to focus on these markers and, based on the literature of the last 5 years, to discuss their real function in the diagnosis and prognosis of the three most frequent malignant bone neoplasms: osteosarcoma, chondrosarcoma, and Ewing sarcoma.

There are several biomarkers and these can be specific or aspecific; diagnostic, prognostic, or therapeutic; serological, genetic, or histological. This group includes a series of serological markers which reflect the osteoblastic and osteoclastic activity of the bone. They can have diagnostic and prognostic value and can be useful in monitoring therapies, although there are no guidelines recommending their use in clinical practice.

Their levels can alter under different conditions, physiological or pathological, and thus they are not specific. In cancer, Biochemical markers are useful to evaluate the dissemination a distance, the response to therapy and survival. Metastases can be classified, based on radiological features, as osteolytic, osteoblastic, or mixed.

The osteoblastic lesions are manifested by high levels of bone turnover markers. High levels of these markers again predict poor prognosis Singer and David, The use of bone markers in malignant tumors allows an early diagnosis, fast start of therapy, limited complications and predict the risk of relapse in patients with early-stage malignant tumors Joerger and Huober, In patients with osteolytic lesions, Elevated levels of urinary NTx causes a greater risk of complications and progression of cancer Singer and David, There is limited evidence that bone turnover markers can be used to predict bone metastases in patients with early-stage malignant tumors, with PINP N-terminal propeptide of type 1 procollagen , ICTP carboxyterminal cross-linked telopeptide of type I collagen and bone sialoprotein BSP , with tumor immunoexpression of BSP being the most studied and discussed.

However, the sensitivity of these markers is very low, suggesting that they cannot be preferred over conventional bone scans in the diagnosis of bone metastases. In bone tumors, molecular diagnostics can increase the accuracy of the diagnosis and assist in subtyping bone tumors.

In their review, Szuhai et al. Different techniques can be used to detect cytogenetic changes, such as banding and multicolor fluorescence in situ hybridization, array comparative genomic hybridization array CGH , targeted detection techniques FISH, RT-PCR and mutation detection techniques.

Recently, Robin et al. The reduction of EYA3 protein has negative effects on the survival of Ewing sarcoma. Yang et al. The authors have shown that all-trans retinoic acid ATRA inhibits the differentiation and growth of human OS through the activation of SMAD, suggesting a possible role for retinoic acid, in addition to classic chemotherapy, in the therapy of OS Yang et al. Saini et al. The peak incidence is at age 10—30 years Bielack and Bernstein, Osteosarcomas predominantly target the long cylindrical bones, including the knee joint approximately half of observations and the humerus Mankin et al.

Among the most affected are the femur, tibia, humerus and, less frequently, shoulder blade, and bones of the pelvis and skull Enneking et al. Eighty percent of all metastases arise in the lungs, most commonly in the periphery of the lungs, and exhibit resistance to conventional chemotherapy Kager et al. Survival of patients has improved with the discovery of new chemotherapies Chou and Gorlick, ; Longhi et al.

The new biotechnological and pharmacological research is directed on the use of markers serum tumor for treatment of osteosarcoma. Several international study groups started a multicenter study on the tumor markers Fuchs et al. Kaseta et al. They performed an immunohistochemical analysis of 35 surgically treated patients with primary OS and 18 tissue specimens from non-malignant osseous lesions.

The authors suggest that none of the genes has a predictive role on survival, but the decrease of 4-year disease-free survival in the group compared with the control group, confirmed that more intensive adjuvant treatment could reduce the recurrence rates of the disease Kaseta et al. Zhao et al.

Luo et al. Their results suggest that alterations in osteoprogenitors may disrupt the osteogenic differentiation pathway. Thus, identifying potential differentiation defects in OS tumors would make it possible to reconstruct the tumorigenic events in osteoprogenitors and to develop rational differentiation therapies for clinical OS management Luo et al.

Based on the concept that glycoproteins and glycosaminoglycans are an integral part of bone and prolonged exposure to fluoride for long duration has been shown to cause degradation of collagen and ground substance in bones, Sandhu et al.

They found that, compared to control groups, serum sialic acid concentration was significantly increased in patients with osteosarcoma and, in a second study, in patients with other bone tumors Sandhu et al. Guo et al. HSPgp96, was mainly expressed in the cytoplasm of osteoblastic sarcoma with less differentiation.

The authors affirm that the HSPgp96 has a role in the pathogenesis of bone tumor, but the marker cannot be used in determining the degree of malignancy and as a target for tumor immunity Guo et al. Babkina et al. Yu et al. Zhang et al. The expression and clinical significance of cysteine-rich protein with Kazal motifs RECK was immunohistochemically examined in 49 osteosarcoma patients by Xu et al.

RECK status is a useful prognostic factor in osteosarcoma and an independent prognostic factor contributing to the determination of more adequate therapy strategies for individual patients Xu et al. Observing that cysteine-rich intestinal protein 1 CRIP1 has a significant prognostic impact in gastric cancer, Baumhoer et al.

They analyzed pre-therapeutic and well-characterized osteosarcoma samples for the immunohistochemical expression of CRIP1 and correlated their findings with clinic-pathological parameters including follow-up, systemic spread and response to chemotherapy. The expression of this factor is predominant in patients with longer survival without metastases Baumhoer et al. Shimizu et al. These factors may reduce the osteogenic differentiation of osteosarcoma cells.

Also Fgf2 helps the proliferation and migration of neoplastic cells, and alters the response of cells to drug therapy.

The block of Fgf2 factor could modulate the progression of osteosarcoma Shimizu et al. Lu et al. The authors, by immunohistochemistry, observed the expression of these two markers in patients with osteosarcoma and osteochondroma.

The authors say that contemporary expression of both proteins is present in advanced stages and promotes the diffusion of the tumor; moreover, gender, age and the morphological variation do not have a significant role Lu et al. Nunez et al. Jin et al. They characterized the differential expression of protein biomarkers in osteosarcoma serum, finding 58 significant protein spot features in osteosarcoma sera.

Further, Western blotting and enzyme linked immunosorbent assay ELISA confirmed decreased levels of gelsolin in the osteosarcoma serum samples Jin et al. Nestin protein has been detected in various malignancies and its expression correlates with advanced grade in some neoplasms. Zambo et al. Using immunohistochemistry and immunofluorescence, they evaluated nestin expression in tumor tissue samples from 45 patients with high-grade osteosarcomas.

Nestin-positive tumor cells were detected in all of the examined osteosarcomas. Using immunofluorescence, high levels of nestin expression were associated with poorer clinical outcomes. Despite the significantly shorter survival rates observed in patients with elevated levels of nestin expression, nestin does not appear to represent a powerful prognostic marker that would be superior to conventional methods Zambo et al.

A study by Tan et al. In addition, the author affirm that this marker is associated with a poor prognosis and spread in the lungs Tan et al. The chemokine, molecules involved in tumor genesis, have been studied by Li et al. The author observed an increase in serum levels in patients with osteosarcoma, particularly CXCL4 and CXCL, and affirmed that the marker play a role in clinical results and new studies are needed for the treatment Li et al.

Sharili et al. The author observed that the expression of this marker is correlated with the severity of the tumor and the risk of metastases. In addition, the biomarker Snail2 is useful in the prognosis of bone tumors Sharili et al.

Interestingly, Funovics et al. The author asserts that CRP is an marker for survival in patients with high-grade tumor, and invites further large-scale studies to confirm these results Funovics et al. Perbal et al. In contrast, assessment for CCN3 expression levels at diagnosis may represent a useful molecular tool for early identification of patients with different prognoses Perbal et al. Gillette et al. However, this cell line provides a useful tool for investigating the molecular mechanisms contributing to osteosarcoma and may have the potential to serve as a culture system for studies involving bone physiology Gillette et al.

De Nigris et al. Zuffa et al. The author notes that the protein protects the DNA of cells, although are not known the mechanisms of protection exactly Zuffa et al. Wei et al. Nathan et al. The author asserts that this cell line allows to identify possible molecular abnormalities that transform the osteoblast into cancer cells Nathan et al.

The role of transcriptional regulators Oct-4 in osteosarcoma has been studied by Levings et al. According to the author this genetic marker plays a biological role in the proliferation and spread of cancer Levings et al. The expression of Mirs was reviewed by He et al. The author states that the action of miRs is pdependent, and causes alteration of proliferation and apoptotic process. He et al. Yang J. Analyzing blood samples of osteosarcoma patients, Hu et al. Mirabello et al.

The 8q24 chromosomal region contains several loci that are associated with the risk of many different cancers. The study suggested that several SNPs in 8q24 may be associated with osteosarcoma, but the susceptibility observed was modest Mirabello et al. Bcl-xL, a member of Bcl-2 protein family functioning as dominant regulators of apoptotic cell death, has been reported to play important roles in malignant transformation and tumor development.

Wang et al. The author, through many genetic techniques, compare the expression of this gene in tumor and non-tumor cells. An increase of Bcl-xL mRNA was observed in cancer cells with metastases compared to non-metastatic cells; also the expression of gene was significantly higher in tissues with tumor compared to healthy ones.

Therefore, the author believes that the increase of the expression of Bcl-xL mRNA has a role in the diffusion of osteosarcoma and can be a useful molecular target for the treatment Wang et al.

Based on many papers reporting that the reduction of expression of Fas protein is correlated to a higher risk of lung metastases and arsenic trioxide ATO may promote cell apoptosis in cancers. Yang G. Lockwood et al. The overexpression of cyclin E1 was linked to potential prognostic and therapeutic implications Lockwood et al. A study performed by the Massachusetts General Hospital group asserts that miRa-3p is involved in proliferative process of osteosarcoma.

The restoration of this marker may provide therapeutic benefits in osteosarcoma. However, the potential roles of miRNAs in osteosarcoma remain largely uncharacterized. By applying a miRNA microarray platform and unsupervised hierarchical clustering analysis, they found that several miRNAs have altered expression levels in osteosarcoma cell lines and tumor tissues when compared with normal human osteoblasts.

Three miRNAs, miRa-3p, miRp and miRc, were significantly decreased in osteosarcoma cell lines compared to osteoblasts, whereas miRp and miR were increased in osteosarcoma cell lines Duan et al. MiRNA genes that play a role in the development and progression of Osteosarcoma. A preliminary study by Folio et al. The potential of cortactin overexpression as a biomarker for osteosarcoma is, in fact, consolidated and transcriptomic profiling has shown cortactin to be overexpressed in pediatric osteosarcoma.

Shen et al. The protein was identified and isolated using GFP antibody Shen et al. Chen et al. Western blot analysis showed that expression of CRM1 an intermediary involved in the transport of essential molecules of the cell, such as proteins and messenger RNA was significantly increased in osteosarcoma compared with normal tissues Yao et al.

Won et al. Salinas-Souza et al. They concluded that GST polymorphisms may have a role in treatment response and osteosarcoma progression Salinas-Souza et al. They also represent ideal targets for the development of tumor specific therapies. This study allowed us to confirm the involvement of known genes and the identification of new genes. The comparison of the data from this study and those published on mesenchymal stem cells has allowed to affirm that these cells are potential precursors of tumor Hancock and Lessnick, Potikyan et al.

Through a genome-wide high-resolution analysis, Savola et al. In most cases, the changes affect the chromosomes 1q, 2, 8,9p, 12, end 16q. The authors conclude that this method could be an effective way of identifying chromosome regions and new genes affected by cancer Savola et al. Bachmaier et al. Guillon et al. Moreover, in reporter gene experiments, the transcription activation is highly dependent on the number of repeats that are included in the construct.

Together, these results indicate the likely contribution of microsatellite elements to long-distance transcription regulation and to oncogenesis Guillon et al. Szuhai et al. The involvement of NFATc2, a transcription factor, determines an abnormal immune response, secondary to altered function of T-cell Szuhai et al.

The author affirms that the hypoxia allows to control EWS-FLI1 expression, resulting in variability of clinical and prognostic features in tumor Aryee et al. Vural et al. The Rizzoli Experience, conducting a molecular diagnosis of EFT over 4 years — , was reported in Erkizan et al.

The minimal interaction region of ESAP1 was characterized and the lysine residues were found to be critical for cellular cytotoxicity. Douglas et al.

Their data showed that BMI-1 is highly expressed by ESFT cells and that, although it does not significantly affect proliferation or survival, BMI-1 actively promotes anchorage independent growth in vitro and tumorigenicity in vivo.

A recent statistical methodology, called ICAN, allows to select genes that play a role in the prognosis and progression of tumors in studies with small samples, was reported by Bennani-Baiti et al. Through this methodology the author affirms that CXCR4 expression increases the risk of tumor metastases, while CXCR7 expression is associated with shorter survival. Consequently, in an integrative genomic study of ES tumors, Mackintosh et al.