Prognostic Factor For Osteosarcoma Patients Research Articles

Downregulation of long non-coding RNA DBH-AS1 inhibits osteosarcoma progression by PI3K-AKT signaling pathways and indicates good prognosis.

Long non-coding RNA DBH-AS1 (DBH-AS1) has emerged as a novel regulator in cancer initiation and progression of several tumors. However, the expression of DBH-AS1 in osteosarcoma and its effect on the tumorigenesis of osteosarcoma are unclear. The purpose of this study was to determine the role of DBH-AS1 in osteosarcoma progression. The expression level of DBH-AS1 in 119 pairs of osteosarcoma tissues and five cell lines was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The association of DBH-AS1 expression with clinicopathological factors and prognosis was also analyzed. Cell proliferation was measured by Cell Counting Kit-8 (CCK-8), EdU and cell colony formation assays and apoptosis in MG63 and U2OS cells was examined by flow cytometry. Following that, transwell invasion and wound-healing assays were used to explore cell migration and invasion, respectively. The expression of the PI3K/Akt pathway-related proteins was examined by Western blot analysis. We observed that DBH-AS1 was distinctly overexpressed in osteosarcoma tissue and cells, and associated with lymph node status and metastasis status. Osteosarcoma patients with a higher DBH-AS1 expression showed significantly poorer overall survival than those with lower DBH-AS1 expression. Multivariate analysis demonstrated that high DBH-AS1 expression was an independent poor prognostic factor for osteosarcoma patients. Functional assays revealed that knockdown of DBH-AS1 inhibited cell proliferation, migration and invasion, while promoted apoptosis in osteosarcoma. Moreover, suppression of DBH-AS1 could inhibit the activation of the PI3K/Akt pathway, which was demonstrated by examining the expression levels of p-PI3K and p-Akt. Our data first reported that DBH-AS1 may act as an oncogenic lncRNA by modulating the PI3K/Akt pathway in osteosarcoma, which may serve as a candidate prognostic biomarker and target for new therapies in osteosarcoma.

A Retrospective Clinicopathological Study of Osteosarcoma Patients with Metachronous Metastatic Relapse.

Purpose: Although osteosarcoma patients receive a standardized treatment, metachronous metastatic relapse still impairs the overall survival (OS). This study aimed to explore the clinicopathological features and prognostic factors of osteosarcoma patients with metachronous metastatic relapse.Patients and methods: We retrospectively analyzed 59 patients, between January 1st, 2004 and December 31st, 2013. Employed Chi-square test to recognize the differences in clinicopathological characteristics between early and late metastatic patients, and the differences between shorter and longer survival patients. Used the Kaplan-Meier method to evaluate the survival data, cox step proportional hazard test to analyze the prognostic factors associated with OS.Results: We found that early metastatic patients were prominently correlated with the male, tumor size ≥8 cm, histological grade G2, Enneking stages II, anatomic location of the distal femur, pathological of conventional types, and elevated alkaline phosphatase (ALP) level at diagnosis, (p<0.05). In parallel, the shorter survival patients were primarily linked to tumor size ≥8 cm, histological grade G2, Enneking stages II, early metastasis, multiple pulmonary metastases, lack of curative treatment after metastasis, increased level of ALP at diagnosis and LDH after metastasis, (p<0.05). The univariate analyses of the prognostic factors showed that patients who had these clinicopathological characteristics, such as male, tumor size ≥8 cm, Enneking stage IIB, multiple pulmonary metastases, lack of curative treatment after metastasis, the elevated ALP at diagnosis, elevated ALP and LDH after metastasis, had a worse OS in osteosarcoma patient with metachronous metastatic relapse, (p<0.05). The multivariate analyses showed that tumor size, type of metastasis and ALP level at diagnosis were independent factors for OS in osteosarcoma patient with metachronous metastatic relapse (p<0.05).Conclusion: These results indicated that osteosarcoma patients with metachronous metastatic relapse have special features which might be utilized to effectively predict the likelihood of early metastatic relapse and the prognosis.

LncRNA TP73-AS1 predicts poor prognosis and functions as oncogenic lncRNA in osteosarcoma.

TP73 antisense RNA 1 (TP73-AS1), a novel long noncoding RNA (lncRNA), has been suggested to be deregulated in various human cancers and serve as a tumor suppressor or promoter, depending on tumor types. The role of TP73-AS1 in osteosarcoma is still unknown. In our results, TP73-AS1 was highly expressed in osteosarcoma tissue samples and cell lines compared with matching adjacent nontumor tissue specimens and a normal human osteoblast cell line, respectively. Moreover, high expression of TP73-AS1 was statistically associated with advanced Enneking stage, large tumor size, present distant metastasis, and poor histological grade, while exhibiting no statistical association with age, sex, and tumor site. The survival analyses showed that patients with osteosarcoma with high expression of TP73-AS1 obviously had lower overall survival than osteosarcoma patients with low expression of TP73-AS1, and high expression of TP73-AS1 was an independent poor prognostic factor for osteosarcoma patients. The experiments in vitro indicated that inhibition of TP73-AS1 expression depressed osteosarcoma cell viability, migration, and invasion, and arrested cell cycle. In conclusion, TP73-AS1 serves as oncogenic lncRNA participated in osteosarcoma progression.

LncRNA SNHG20 is associated with clinical progression and enhances cell migration and invasion in osteosarcoma.

SNHG20 is a novel lncRNA which has been showed to be overexpressed and functions as oncogenic lncRNA in several types of human cancer. The role of SNHG20 in osteosarcoma is still unknown. The purpose of our study was to identify the clinical value and biological function of SNHG20 in osteosarcoma. Our results indicated SNHG20 was overexpressed in osteosarcoma tissues and cell lines compared with paired non-tumor tissues and normal human osteoblast cell line, respectively. Moreover, we observed high-expression of SNHG20 was obviously associated with Enneking stage, distant metastasis, and histological grade. SNHG20 expression was negatively associated with overall survival, and high-expression of SNHG20 was an independent unfavorable prognostic factor in osteosarcoma patients. Furthermore, SNHG20 promoted osteosarcoma cell migration and invasion through modulating epithelial-mesenchymal transition -associated genes. In conclusion, SNHG20 is an independent unfavorable prognostic factor in osteosarcoma patients, and functions as an oncogenic lncRNA to modulate tumor cell migration and invasion. © 2018 IUBMB Life, 70(11):1115-1121, 2018.

The outcomes and prognostic factors in patients with osteosarcoma according to age: a Japanese nationwide study with focusing on the age differences

BackgroundFew reports have described clinical features, prognosis and prognostic factors of osteosarcoma patients according to age.MethodsUsing the Bone and Soft Tissue Tumor Registry in Japan, we identified 1043 osteosarcoma patients including 760 who were younger than 40 years, 173 aged between 41 and 64 years, and 110 patients older than 65 years. We extracted data on patient demographics and prognosis. Prognostic factors for patients older than 65 years or other age groups were analyzed.ResultsPatients older than 65 years showed a significantly higher proportion of tumors arising in the trunk and with metastasis at diagnosis, and their 5-year disease-specific survival (DSS) rate was 32.7%. Multivariate analysis showed that the presence of metastasis at diagnosis [hazard ratio (HR): 3.04; 95% confidence interval (CI), 1.63–5.69; P < 0.001] and tumors > 16 cm in size (HR: 2.84 compared with < 8 cm; 95% CI, 1.16–6.97; P = 0.023) were significantly associated with worse DSS. The 5-year DSS was 39.1% in 80 patients older than 65 years without metastasis at diagnosis. Methotrexate was used in only 5.0% of these patients. Adjuvant chemotherapy was not significantly associated with better DSS (P = 0.323) in this generation and aged between 41 and 64 years (P = 0.566), although adjuvant chemotherapy yielded significantly better survival in patients younger than 40 years (P < 0.001).ConclusionsAnalysis of this cohort of osteosarcoma patients revealed some unique clinical, therapeutic and prognostic features according to age groups in the largest cohort. Adjuvant chemotherapy was not associated with a better DSS in the group of patients aged between 41 and 64 years or older than 65 years.

LncRNA CBR3-AS1 predicts unfavorable prognosis and promotes tumorigenesis in osteosarcoma

LncRNA CBR3-AS1 has been suggested to promote malignancy in several types of human cancers, but the clinical significance and biological function of lncRNA CBR3-AS1 in osteosarcoma is still unknown. The purpose of our study is to explore the clinical significance of lncRNA CBR3-AS1 in osteosarcoma patients and the biological function in osteosarcoma cells. In our results, we found lncRNA CBR3-AS1 was highly-expressed in osteosarcoma tissues and cell lines, and associated with Enneking stage, distant metastasis and histological grade. Survival analysis indicated that the high-expression of lncRNA CBR3-AS1 was an independent poor prognostic factor for osteosarcoma patients. Loss-of-function studies showed knockdown of lncRNA CBR3-AS1 suppressed osteosarcoma cells proliferation, migration and invasion, and promotes cells apoptosis, but had no effect on cell-cycle distribution. There was no association between lncRNA CBR3-AS1 and CBR3 expression in osteosarcoma tissues, and knockdown of lncRNA CBR3-AS1 had no effect on CBR3 mRNA and protein expression osteosarcoma cells. In conclusion, lncRNA CBR3-AS1 serves an oncogenic role to regulate osteosarcoma cells proliferation, migration, invasion and apoptosis, and is an independent poor prognostic factor for osteosarcoma patients.

A novel circulating hsa_circ_0081001 act as a potential biomarker for diagnosis and prognosis of osteosarcoma.

Chemo-resistance and lung metastasis have been the two obstacles in the osteosarcoma (OS) treatment, which is still lack of effective biomarkers for prediction, diagnosis and treatment. Circular RNA (circRNA) is a new type of endogenous noncoding RNA that could serve as ideal biomarkers in cancer because of its stable loop structure. However, little is known about the diagnostic value of circRNAs in OS as well as their associations with clinicopathologic characteristics of OS patients. In the current study, we identified a novel circRNA, hsa_circ_0081001, screened by the RNA sequencing in the three paired chemo-resistant and chemo-sensitive OS cell lines (MG63/DXR vs MG63, KHOS/DXR vs KHOS, U2OS/DXR vs U2OS), and found that hsa_circ_0081001 was significantly up-regulated in the OS cell lines, tissues and serums, associated with poor overall survival and cox multivariate analysis showed that hsa_circ_0081001 was a novel independent prognostic factor for OS patients. Then, receiver operating characteristic (ROC) curve analysis revealed that hsa_circ_0081001 could act as a biomarker for the OS diagnosis and prognosis prediction, better than alkaline phosphatase (ALP) and lactate dehydrogenase (LDH). In addition, we preliminarily found that hsa_circ_0081001 expression level may dynamically monitor and reflect the condition changes of OS patients in a small-scale prospective clinical pretest. In conclusion, our study suggested that circulating hsa_circ_0081001 could serve as a potential biomarker and therapeutic target for OS patients.

Abstract 2125: Flavokawain A, a kava chalcone, inhibits growth and invasion of human osteosarcoma cells by targeting Skp2

Abstract Purpose: Osteosarcoma (OS) is the most common primary bone malignancy with a high propensity for local invasion and distant metastasis. Flavokawain A (FKA), a major chalcone from kava extract, has been reported to have antitumor effects on multiple cancer cell lines. The consumption of kava-containing beverage has been associated with a low cancer incidence. In a previous report, mice treated with high-dose FKA did not demonstrate any significant major organ toxicity. However, the efficacy and anticancer mechanisms of FKA in OS is still to be elucidated. Experimental Design: OS cell lines were treated with increasing dosage of FKA and tested for cell motility, proliferation, and invasion by MTT assay and Matrigel invasion assay. Cell cycle analysis was performed using flow cytometry. We examined Skp2 expression in several OS cell lines using western blot and in patient tissue array by immunostaining. Kaplan-meier analysis and log rank test were used to compare overall survival. Both Skp2-dependent cell cycle progression and Skp2-related RhoA expression were also examined after FKA treatment. The effects of FKA on lung metastasis were evaluated after orthotopic injection of OS cells into the tibia. Results: We show that FKA inhibits the growth and motility of multiple OS cell lines in vitro. Flow cytometry analysis confirms cellular apoptosis and arrest in G2/M phase after FKA treatment, whereas cellular invasion is also inhibited in a dose-dependent manner. Skp2 is expressed in several OS cell lines and is associated with a poor prognosis in OS patients. Skp2 levels in OS cell lines decreased after FKA treatment. The expression of cell cycle regulators including p21 and p27, which are downstream of Skp2, was upregulated. Moreover, Skp2-related RhoA expression is inhibited by FKA and confirmed at protein level. Conclusions: Taken together, the evidence suggests FKA exerts anti-invasive effects in association with Skp2-dependent cell cycle progression and Skp2-related RhoA expression. Since Skp2 is a negative prognostic factor for OS patients, FKA should be investigated further as an anti-Skp2 therapeutic strategy for OS. Citation Format: Yidan Zhang, Wendong Zhang, Nikolas Zaphiros, Xiuquan Du, Pratistha Koirala, Michael Roth, Jonathan Gill, Sajida Piperdi, David Geller, Rui Yang, Jinghang Zhang, Richard Gorlick, Xiaolin Zi, Tao Ji, Bang H. Hoang. Flavokawain A, a kava chalcone, inhibits growth and invasion of human osteosarcoma cells by targeting Skp2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2125. doi:10.1158/1538-7445.AM2017-2125

Increased Six1 expression is associated with poor prognosis in patients with osteosarcoma.

Sine oculis homeobox homolog 1 (Six1) is an evolutionarily conserved transcription factor that acts as master regulator of development and is frequently dysregulated in various types of cancer. Six1 has been demonstrated to be upregulated in human osteosarcoma cell lines compared with osteoblastic cell lines. However, the association of Six1 expression with the progression and prognosis of osteosarcoma patients remains unclear. The purpose of the present study was to investigate the association between Six1 expression and the clinicopathological characteristics and prognosis of osteosarcoma. Six1 protein was detected by immunohistochemistry in a series of 100 osteosarcoma patients, and Kaplan-Meier survival analysis was performed to assess prognosis. The results revealed that increased Six1 protein expression was prevalent in osteosarcoma and was significantly associated with Enneking stage (P=0.002) and tumor size (P=0.010). Additionally, according to the log-rank test and Cox regression model, expression of Six1 is indicated to be an independent prognostic factor in osteosarcoma patients. In summary, positive expression of Six1 protein is closely associated with the tumor progression and poor survival of osteosarcoma patients. The results suggest that Six1 is a overexpressed in individuals with poor prognosis, and may thus be used as a prognostic biomarker in patients with osteosarcoma.

Prognostic significance of chemotherapy-induced necrosis in osteosarcoma patients receiving pasteurized autografts.

BackgroundAmong various reconstruction methods after wide excision for osteosarcoma, pasteurized autograft is often preferred. While the whole area of the tumor can be assessed for chemotherapy-induced necrosis, one of the important prognostic factors, in other reconstructive techniques, only a portion removed from a wide-resection specimen is available when using pasteurized autograft method. The assessment, therefore, may be unreliable. We analyzed the prognostic significance of the chemotherapy-induced necrosis in osteosarcoma patients who underwent reconstruction with pasteurized autografts.Patients and methodsWe reviewed the records of osteosarcoma patients who underwent treatment in our institution from 1998 to 2013. Cases of reconstruction with pasteurized autografts were defined as the patient group, and the same number of patients who underwent other reconstruction methods served as controls. Chemotherapy-induced necrosis was evaluated for removed extra-osseous and curetted intramedullary tumor tissues.ResultsA total of 22 patients were identified; the median age was 15.5 years, and there were 12 males. The most common tumor location was the distal femur. The most common histological subtype was osteoblastic. Median size was 8.1 cm. Disease status was stage IIB in 13 patients and IIA in 9. Median follow-up was 76 months. No differences between the patient and control groups were observed in potential prognostic factors, overall survival, metastasis-free survival, or recurrence-free survival. Univariate analyses demonstrated that histological response was a significant prognostic factor for metastasis-free survival and also significant for recurrence-free survival.ConclusionChemotherapy-induced necrosis grading, using only available tumor tissues, could be a prognostic factor for osteosarcoma patients receiving pasteurized autografts for reconstructive surgery.

MicroRNA-125a Regulates Cell Proliferation Via Directly Targeting E2F2 in Osteosarcoma

Background/Aims: Increasing evidence has shown that miR-125a plays important role in human cancer progression. However, little is known about the function of miR-125a in osteosarcoma. Methods: The expression of miR-125a in osteosarcoma tissues and cell lines were examined by qRT-PCR. The biological role of miR-125a in osteosarcoma cell proliferation was examined in vitro. The targets of miR-125a were identified by a dual-luciferase reporter assay. Results: The results showed that the expression of miR-125a expression is significantly lower in osteosarcoma tissues and cell lines. Survival curves showed that the survival of patients in high miR-125a expression was significantly longer than that of patients with low miR-125a expression, and multivariate analysis suggested that miR-125a is an independent prognostic factor for osteosarcoma patients. In addition, it was found in this study that miR-125a can inhibit the growth of osteosarcoma cells. The dual-luciferase reporter assay demonstrated that E2F2 is a novel target gene for miR-125a. In addition, in a recovery experiment, it was shown that miR-125a inhibits the biological function of osteosarcoma cells by inhibiting the expression of E2F2. Conclusion: Our results suggest that miR-125a acts as a tumor suppressor via regulation of E2F2 expression in osteosarcoma progression, and miR-125a may represent a novel therapeutic target for the treatment of osteosarcoma.

Up-regulation of long noncoding RNA CCAL predicts poor patient prognosis and promotes tumor metastasis in osteosarcoma.

Long noncoding RNAs (lncRNAs) play essential roles in tumor progression. Aberrant colorectal cancer-associated lncRNA (CCAL) has been found in colorectal cancer. However, the function of lncRNA CCAL in osteosarcoma (OS) remains unclear. Quantitative real-time PCR (qRT-PCR) was performed to measure CCAL expression in OS tissues and adjacent nontumor tissues. The correlation betweent CCAL expression and clinicopathological features and prognosis was also analyzed. In addition, the function of CCAL was further evaluated by cell proliferation, migration and invasion assays. We showed that CCAL was significantly up-regulated in OS tissues compared with adjacent nontumor tissues. Increased expression of CCAL was correlated with advanced TNM stage and metastasis. Kaplan-Meier analysis demonstrated that patients with high CCAL expression had lower overall survival than those with low CCAL expression. Multivariate Cox regression analysis indicated that CCAL expression might be an independent prognostic factor for OS patients. In addition, functional assays showed that decreased CCAL expression could inhibit OS cell proliferation, migration and invasion ability. Our findings suggested that CCAL plays critical roles in OS progression and could act as a therapeutic target in the treatment of OS.

Overexpression of pyruvate kinase M2 predicts a poor prognosis for patients with osteosarcoma.

It is stated that high expression of pyruvate kinase (PKM2) emerges as a significant player in the metabolism and progression of various human malignancies. However, the expression of PKM2 and its association with the prognosis of osteosarcoma had not yet been studied. In the present study, the expression and biological significance of PKM2 in osteosarcoma were investigated. We found that PKM2 expression was elevated in the cancerous tissues and it was more abundant than the adjacent normal tissues (60.2 vs 26.1%, p<0.001). Moreover, we showed that high PKM2 expression was positively correlated with Enneking stage (p=0.006) and distant metastasis (p=0.007) but not with the age, gender, tumor site, tumor size, histologic grade, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and local pain of the patients. Furthermore, Kaplan-Meier analysis revealed that the overall survival (OS) for patients with high PKM2 expression was significantly lower than those with low PKM2 expression (p<0.001). Finally, multivariate analysis revealed that high PKM2 expression was an independent prognostic factor for osteosarcoma patients (p=0.004). Collectively, these data indicated that elevated PKM2 might serve as a novel target for the treatment of osteosarcoma.

Clinical and biological significance of PIM1 kinase in osteosarcoma.

Osteosarcoma is the most prevalent histological form of primary malignant bone tumor. The majority of osteosarcoma patients have limited alternative therapeutic options and metastatic patients generally have a poor prognosis. Proto-oncogene serine/threonine-protein kinase PIM1 is associated with growth and survival of many kinds of tumor cells. However, the role of PIM1 in osteosarcoma remains largely unknown. In this study, we investigated the functional and therapeutic relevance of PIM1 as a putative target in osteosarcoma. We found PIM1 was highly expressed in various osteosarcoma cell lines and in tumor tissues from osteosarcoma patients. Tissue microarray and immunohistochemistry analysis showed that the overall and disease-free survival rate of patients with high levels of PIM1 protein expression were significantly shorter than patients with low levels. High levels of PIM1 were also associated with present metastasis and can be considered as an independent prognostic factor in osteosarcoma patients. Knockdown of PIM1 expression by synthetic siRNA or shRNA greatly inhibited cell growth, migration, and invasion. Moreover, these changes accompanied with down-regulation of anti-apoptotic protein Bcl-2. The similar results were obtained in osteosarcoma cells treated with PIM1 specific inhibitor (SMI-4a). These results suggest that PIM1 kinase is critical for the growth and metastasis of osteosarcoma cells and can be a potential therapeutic target for osteosarcoma treatment. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1185-1194, 2016.

Associations of polymorphisms in the bone morphogenetic protein-2 gene with risk and prognosis of osteosarcoma in a Chinese population.

Osteosarcoma is the most common type of bone cancer in adolescence. Bone morphogenetic protein-2 (BMP-2) plays important roles in the development of bone and cartilage and in inhibiting the tumorigenicity of cancer stem cells in human osteosarcoma cell line. The aim of this study was to examine whether polymorphisms in the BMP2 gene are associated with osteosarcoma risk and prognosis in Chinese population. Five single nucleotide polymorphisms (SNP) in the BMP2 gene were genotyped in a case-control study, including 203 osteosarcoma patients and 406 cancer-free controls. We found that rs3178250 TT genotype was associated with significant increased osteosarcoma risk (age-adjusted odds ratio (OR) = 2.06, 95% confidence intervals (CI) of 1.23-3.45) compared with CC genotype. Subjects carrying the AA genotype of rs1005464 had significant decreased cancer risk (age-adjusted OR = 0.44, 95% CI of 0.23-0.85) compared with those carrying the GG genotype. Haplotype analysis also showed that carriers of the G-T-T-G and A-T-T-G haplotypes (rs235764-rs3178250-rs235768-rs1005464) had significant increased risks of osteosarcoma (age-adjusted OR = 1.85, 95% CI of 1.28-2.66 and age-adjusted OR = 1.51, 95% CI of 1.06-2.16) compared with the G-C-T-A haplotype carriers. Besides, rs1005464 was an independent prognostic factor for osteosarcoma patients (GA vs. GG: age-adjusted hazard radio (HR) = 0.60, 95% CI of 0.36-0.99). Our data suggest that genetic mutations in the BMP2 gene are associated with osteosarcoma risk and prognosis in a Chinese population.

Factors predicting survival following complete surgical remission of pulmonary metastasis in osteosarcoma.

Pulmonary metastasectomy (PM) is associated with improved survival of patients with metastatic osteosarcoma; however, the factors affecting survival following achievement of complete surgical remission remain controversial. The main objective of this study was to report the outcomes and prognostic factors of osteosarcoma patients who achieved complete remission (CR) following PM. We analyzed the effect of demographic and disease-related characteristics on the overall survival (OS) of consecutive patients with metastatic osteosarcoma who were treated at a single institution and achieved CR following PM, through univariate and multivariate analyses. Between January, 2000 and August, 2013, 62 patients with metastatic osteosarcoma were treated and followed up at our institution. A total of 25 patients achieved CR following PM and were included in this analysis. The 5-year OS and disease-free survival following PM were 30 and 21%, respectively. The factors correlated with inferior OS in the univariate analysis included chondroblastic subtype, post-chemotherapy necrosis <90% in the primary tumor, metastasis detected during neoadjuvant or adjuvant chemotherapy and pathological identification of tumor cells reaching the visceral pleural surface of any of the resected nodules. In the multivariate analysis, the chondroblastic subtype was the sole independent adverse prognostic factor (HR=4.6, 95% CI: 1.0-21.3, P=0.044). Therefore, factors associated with tumor biology, including poor tumor necrosis in the primary tumor and detection of metastasis during primary chemotherapy, are associated with poor post-metastasectomy survival. In addition, chondroblastic subtype and visceral pleural involvement predicted poor prognosis in our series.

Prognostic significance of HLA EMR8-5 immunohistochemically analyzed expression in osteosarcoma

BackgroundDefects in Human Leukocyte Antigen (HLA) class I antigen expression and/or function in tumor cells have been extensively investigated, because of their potential role in the escape of tumor cells from T cell recognition and destruction. The researchers evaluated HLA class I expression in tumor tissue as a prognostic factor in osteosarcoma patients and as a predictor of their survival. This retrospective cohort study was conducted at the pathology laboratory of Ain Shams University Hospital, and Ain Shams University Specialized Hospital during the period between January 2009 and January 2012.MethodsThe researchers investigated HLA class I expression in primary osteosarcoma by immunohistochemistry using EMR8-5 mAbs. Furthermore, researchers evaluated the correlation between HLA class I expression and the clinicopathological status and outcome in formalin fixed paraffin embedded tissues from thirty six (36) patients with osteosarcoma.ResultsA high expression of HLA class I was detected in 18 (50) % of tumor samples examined; while tumors with low or negative expression represented 9 (25%) cases each. Data indicate that the overall survival rate of patients with tumors highly expressing HLA class I was significantly higher than those with low or negative expression.ConclusionDown-regulation of class I antigen expression is associated with features of aggressive disease and a poorer prognosis. Therefore, it is imperative to identify HLA as a prognostic factor at the time of diagnosis to detect chemotherapy-resistant tumors and to generate a modified treatment regimen.Virtual slidesThe virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1159334857109547.

High expression of periostin is dramatically associated with metastatic potential and poor prognosis of patients with osteosarcoma.

BackgroundRecent studies have found that periostin (PN), as a kind of secreted glycoprotein, is closely related to the metastatic potential and prognosis of many kinds of tumors. This study aimed to examine the expression of PN in patients with osteosarcoma and explore the relationship of PN expression with clinicopathologic factors and prognosis.MethodsPN was detected by histopathological and immunohistochemical methods in 62 cases of osteosarcoma and 62 of osteochondroma. Detailed pathological and clinical data were collected by reviewing medical records.ResultsThe results showed that increased PN protein expression was prevalent in osteosarcoma and was significantly associated with pathologic subtype (P =0.000), tumor size (P =0.016) and Enneking stage (P =0.047). Additionally, expression of PN was found to be an independent prognostic factor in osteosarcoma patients. High expression of PN protein is closely correlated to the tumor progression and poor survival of osteosarcoma.ConclusionsOur data suggest that PN is a promising biomarker for identifying individuals with poor prognostic potential and suggests its possible use as a prognostic marker in patients with osteosarcoma.

Osteosarcoma in the elderly over 60 years: A multicenter study by the Japanese musculoskeletal oncology group

Few studies have described the characteristics and prognostic factors of osteosarcoma patients aged over 60 years. The Japanese Musculoskeletal Oncology Group (JMOG) carried out a retrospective review of patients over the age of 60 years with osteosarcoma. Only 12 patients had secondary osteosarcoma, with none associated with Paget's disease. The primary disease sites were the extremities in 63% and trunk in 33%. The overall survival was 42.8% and disease-free survival was 40.8% at 5 years in the high grade group. An univariate analysis indicated that significant poor prognostic factors for overall survival were axial location, lung metastasis at initial presentation, and absence of surgical treatment. Multivariate analysis revealed that a significant poor prognostic factor for overall survival was the absence of surgical treatment. Secondary osteosarcoma did not lower the overall or the disease-free survival in any group. The current study indicates that the number of osteosarcoma patients over 60 years is increasing. The number of cases with secondary osteosarcoma over 60 years is relatively small in Japan, with no patients having osteosarcomas related to Paget's disease. Although there is a predilection for axial localization, surgical treatment has a significant impact on patient's prognosis.

Survivin as a Prognostic Factor for Osteosarcoma Patients

Purpose: Survivin is one of the apoptosis inhibitor genes and is rarely expressed in adult ­tissues. However, survivin expression has been detected in various human cancers and ­correlations have been recognized between the level of expression of this gene in tumors and prognosis. In this study, we investigated the correlations between survivin mRNA expres­sion in osteosarcoma tissues and clinicopathological parameters.Methods: There were 22 osteosarcoma patients in our hospital with paraffin-embedded ­tissues which could be extracted from biopsy specimens. We used the RT-PCR method after extracting total RNA and conducted a densitometric analysis to determine the ratio of survivin relative to h-GAPDH as an internal marker.Results: Expression of survivin mRNA was detected in all osteosarcoma samples. Patients with metastasis had high survivin mRNA levels in initial biopsy specimens (p<0.01). Moreover, there was a statistically significant difference in survivin mRNA expression between ­patients with and without metastasis (p<0.01).Conclusion: We concluded that high levels of survivin mRNA expression suggest poor prognosis for osteosarcoma patients.