Significance of Histone H3.3 (G34W)-Mutant Protein in Pathological Diagnosis of Giant Cell Tumor of Bone.

OBJECTIVE: This study aimed to examine the expression of Histone H3.3 glycine 34 to tryptophan (G34W) mutant protein in Giant Cell Tumor of Bone (GCTB). METHODS: This analytic observation research used a cross-sectional study design on 71 bone tumors. The cases involved 54 tissue samples diagnosed as GCBT. It was divided into GCTB primer (n=37), recurrent GCTB (n=5), GCTB with metastasis (n=9), and malignant GCTB (n=3). There were 17 samples mimics of GCTB also tested, including chondroblastoma (n=1), giant cell reparative granuloma (n=2), giant cell of tendon sheath (n=7), chondromyxoid fibroma (n=2), aneurysmal bone cyst (n=2), and giant cell-rich osteosarcoma (n=3). The Immunohistochemistry was used to evaluate the expression of G34W-mutated protein in these bone tumors. RESULT: The representation H3.3 (G34W) was expressed in the nuclei of mononuclear stromal cells but not stained on osteoclast-like giant cells. This study was analyzed by the Chi-square test, Fisher's test, specificity test, and sensitivity test. We obtained p = 0.001 for Histone H3.3 (G34W) mutant expression in GCTB vs Non-GCTB. Statistically, there was no significant difference in the expression level of Histone H3.3 (G34W) in the GCTB and its variants p-value = 0.183. We also obtained that the specificity of Histone H3.3 expression on GCTB was 100% and the sensitivity of Histone H3.3 on GCTB was 77.8%. CONCLUSION: Histon H3.3 mutant as a mutated driver gene in an Indonesian GCTB can assist to diagnose GCTB and compare it from other bone tumors.

A meta-analysis supports core needle biopsy by radiologists for better histological diagnosis in soft tissue and bone sarcomas.

BACKGROUND: Although surgical biopsy has historically been considered to be the standard diagnostic biopsy for soft tissue and bone sarcomas, recent literature suggests that percutaneous core needle biopsy yields similar results. Therefore, an evaluation of the exact diagnostic accuracy and associated influential variables of core needle biopsy that is based on a large data set would be useful. METHODS: We searched MEDLINE, Web of Science, and EMBASE to identify core needle biopsy studies for predicting final histological subtypes of musculoskeletal lesions. The diagnostic accuracies of core needle biopsy and of surgical biopsy were assessed and compared by using random-effect meta-analyses. The factors relevant to diagnostic accuracy were evaluated by meta-regression and subgroup analyses. RESULTS: We selected 32 studies comprising 7209 musculoskeletal lesions. The pooled proportion estimate for the diagnostic accuracy of core needle biopsy was 0.84 (95% confidential interval, CI: 0.81-0.87), which indicated an approximate 84% concordance between core needle biopsy results and final histological diagnoses. The findings of meta-regression and subgroup analyses suggested that radiologists were better core needle biopsy operators than surgeons. An additional meta-analysis for direct comparison between core needle biopsy and surgical biopsy demonstrated that diagnostic accuracy was significantly lower for core needle biopsy than for surgical (pooled odds ratio: 0.39, 95% CI: 0.20-0.76). CONCLUSION: Our results suggested that core needle biopsy should be performed by expert radiologists and that surgical biopsy should be performed if diagnosis following core needle biopsy does not match the clinical presentation and radiographic findings.

Metastatic tumor cells detection and anti-metastatic potential with vesicular stomatitis virus in immunocompetent murine model of osteosarcoma.

Sarcomas are associated with a high incidence of lung metastasis, which leads to a high-risk of cancer death. This study was performed to explore the pre-clinical theranostic potential of a novel fully functional recombinant vesicular stomatitis virus carrying imaging gene Katushka (rVSV-K), as virotherapy and circulating tumor cells (CTCs) detection in the syngeneic mouse model of osteosarcoma with spontaneous pulmonary metastases. Recombinant VSV-K was generated and evaluated in vitro on human and murine osteosarcoma cells. Spontaneous osteosarcoma metastases were established in immune-competent mice by implanting subcutaneously syngeneic osteosarcoma LM8 cells. The vector was injected into the tumor-bearing mice via jugular vein either once or repeatedly. To assess effectiveness, primary tumor growth and development of lung metastasis as well as survival were evaluated. We found that rVSV-K efficiently replicated in and killed all osteosarcoma cell lines in time-dependent manners. Both single or repeated systemic injections of the virus did not inhibit the growth of the primary tumor, but the repeated administration could effectively suppress the development of lung metastases and was likely responsible for the observed increase in survival. Furthermore, we demonstrated, for the first time, that CTCs in blood samples from syngeneic osteosarcoma-bearing mice were successfully detected by utilizing rVSV-K ex vivo. Our results show that repeated systemic injections of rVSV-K are an effective anti-metastatic agent against osteosarcoma in immune-competent mice and this virus to be a useful tool for detection of osteosarcoma CTCs, suggesting that further development of future viral-based theranostic approach in patients with osteosarcoma is warranted. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2562-2569, 2018.

Value of diffusion-weighted imaging for evaluating chemotherapy response in osteosarcoma: A meta-analysis.

The histological examination of the tumor necrosis upon surgery remains the most reliable prognostic factor for osteosarcoma. However, the detection of more early prognostic factors is desirable in order to increase the survival rates and decrease the risk rates for iatrogenic toxicity. The purpose of the current systematic review and meta-analysis was to provide an up-to-date summary of the role of diffusion-weighted imaging (DWI) for the preoperative assessment of the chemotherapy response in osteosarcoma. Articles evaluating DWI for the preoperative assessment of the chemotherapy response of osteosarcoma were systematically searched for in four electronic literature databases. The mean difference in apparent diffusion coefficient (ADC) following neoadjuvant chemotherapy between good and poor histological responders was assessed in 5 studies. The mean difference in the ADC ratio (the percentage change in ADC between post-neoadjuvant and pre-neoadjuvant chemotherapy) reported in 3 studies was also assessed. Five articles with 106 patients fulfilled all of the inclusion criteria for the meta-analysis. Significant mean differences were found between good and poor responders in the ADC in the 5 studies (P=0.03) and the ADC ratio in the 3 studies (P<0.00001). The good responders demonstrated a higher ADC and a higher ADC ratio than the poor responders. DWI performed with ADC values was useful for predicting the chemotherapeutic response of osteosarcoma. This method may have promising potential as a preoperative non-invasive modality.

Long-term survival after sporadic and delayed metastases of conventional osteosarcoma: A case report.

Histologically conventional osteosarcoma, once metastasized to the lung, generally causes a rapid and fatal outcome. Osteosarcoma metastasis to the gastrointestinal tract is extremely rare.We report herein a case of osteoblastic osteosarcoma with exceptionally unique features: sporadic lung metastases and delayed metastases to the stomach and the jejunum with long-term survival. She received multiple operations and chemotherapies, but consequently died of peritoneal dissemination. A review of the literature on osteosarcoma metastasis to the gastrointestinal tract is presented.This patient was very unusual in terms of a long-term survival and metastatic sites, suggesting the importance of vigilance and thorough follow-up for patients with conventional osteosarcoma.

Percent slope analysis of dynamic magnetic resonance imaging for assessment of chemotherapy response of osteosarcoma or Ewing sarcoma: systematic review and meta-analysis.

OBJECTIVE: The objective of this systematic review is to provide an up-to-date and unprecedented summary of percent slope analysis of dynamic magnetic resonance imaging (MRI) for the preoperative evaluation of the chemotherapy response of osteosarcoma or Ewing sarcoma. MATERIALS AND METHOD: Studies evaluating dynamic MRI for the preoperative evaluation of the chemotherapy response of osteosarcoma or Ewing sarcoma were systematically searched for in MEDLINE, EMBASE, and Web of Science. More than 60 % reduction of the slope of the time intensity curve derived from dynamic MRI was defined as a positive response. Pooled sensitivity and specificity for each study were calculated into 2 × 2 contingency tables. The DerSimonian-Laird random-effects method was used for determining the pooled diagnostic odds ratio and the area under curve (AUC) of the summary receiver operating characteristic (SROC) curve. RESULTS: A total of six studies with 66 patients who fulfilled all of the inclusion criteria were considered for the meta-analysis. The pooled sensitivity and specificity were 0.73 (95 % CI, 0.54-0.88) and 0.83 (95 % CI, 0.67-0.94), respectively. A significant difference was found between the good and poor responders in the diagnostic odds ratio. The SROC curve showed that the AUC was 0.839, indicating diagnostic accuracy in estimating good therapy response. CONCLUSION: The slope of the time intensity curve derived from dynamic MRI was useful for evaluating the histological response of patients to neoadjuvant chemotherapy in osteosarcoma or Ewing sarcoma.

Prognostic significance of (18)F-FDG PET at diagnosis in patients with soft tissue sarcoma and bone sarcoma; systematic review and meta-analysis.

PURPOSE: The usefulness of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) for the survival prognosis in soft tissue sarcoma (STS) and bone sarcoma (BS) is controversial. The objective of this systematic review was to provide an up-to-date and unprecedented summary of the prognostic value of (18)F-FDG PET at diagnosis in STS and BS. METHODS: Studies evaluating pre-treatment (18)F-FDG PET for overall survival of STS and BS were systematically searched for in MEDLINE, EMBASE, and Web of Science. Comparative analyses of the pooled hazard ratios (HR) of overall survival were performed between patients with high and low maximum standardised uptake value (SUVmax). The quality of study designs was evaluated using the Newcastle-Ottawa scale (NOS) for quality assessment of cohort studies. P < 0.05 was defined as statistically significant. RESULTS: A total of six studies comprising 514 patients with STS and BS were considered for the meta-analysis. The pooled HR for overall survival was 1.22 (95% confidence interval: 1.03-1.46), suggesting that high SUVmax predicts a significantly shorter overall survival period than low SUVmax (P = 0.03). Additional subgroup analyses using patients with STS alone showed that high SUVmax might predict poorer overall survival than low SUVmax (P = 0.004), although only two studies consisting of 96 patients were included. The overall quality of the included studies evaluated by the NOS assessment was adequate. CONCLUSION: (18)F-FDG PET at diagnosis provides a very useful predictive tool for patients with STS and BS.