Tissue Microarray Immunohistochemical Detection of Brachyury Is Not a Prognostic Indicator in Chordoma

Zhang, Linlin; Guo, Shang; Schwab, Joseph H.; Nielsen, G. Petur; Choy, Edwin; Ye, Shunan; Zhang, Zhan; Mankin, Henry J.; Hornicek, Francis J.; Duan, Zhenfeng

doi:10.1371/journal.pone.0075851

Cited by 35 publications

(37 citation statements)

References 23 publications

(34 reference statements)

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“…Zhang and associates used a tissue microarray to evaluate the effects of the brachyury expression level on the overall survival rate. Their study found no correlation between the brachyury expression level and clinical situations that indicate a poor prognosis [111].…”

Section: Brachyurymentioning

confidence: 93%

The molecular aspects of chordoma

et al. 2015

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Chordomas are one of the rarest bone tumors, and they originate from remnants of embryonic notochord along the spine, more frequently at the skull base and sacrum. Although they are relatively slow growing and low grade, chordomas are highly recurrent, aggressive, locally invasive, and prone to metastasize to the lungs, bone, and the liver. Chordomas highly and generally show a dual epithelial-mesenchymal differentiation. These tumors resist chemotherapy and radiotherapy; therefore, radical surgery and high-dose radiation are the most used treatments, although there is no standard way to treat the disease. The molecular biology process behind the initiation and progression of a chordoma needs to be revealed for a better understanding of the disease and to develop more effective therapies. Efforts to discover the mysteries of these molecular aspects have delineated several molecular and genetic alterations in this tumor. Here, we review and describe the emerging insights into the molecular landscape of chordomas.

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Section: Brachyurymentioning

confidence: 93%

The molecular aspects of chordoma

et al. 2015

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“…Representative areas of 100 paraffin-embedded osteosarcoma tumor specimens for each case were selected and prepared as previously described (32). Briefly, three areas of tumor parts per case were selected for assembling the recipient master block to ensure accurate representation of the selected cores.…”

Section: Methodsmentioning

confidence: 99%

Programmed Cell Death Ligand 1 Expression in Osteosarcoma

Shen¹,

Coté²,

Choy³

et al. 2014

Cancer Immunology Research

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162

137

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Programmed cell death 1 ligand 1 (PD-L1, B7H1) is a cell-surface protein that suppresses the cytotoxic CD8+ T cell-mediated immune response. PD-L1 expression and its clinical relevance in sarcomas are not well understood. Therefore, we sought to measure RNA expression levels for PD-L1 in 38 clinically annotated osteosarcoma tumor samples, and aimed to determine if PD-L1 expression correlates with clinical features and tumor-infiltrating T-lymphocytes (TILs). Quantitative real-time RT-PCR for PD-L1 was optimized in 18 cell lines, of which 5 were osteosarcoma-derived. qRT-PCR results were validated via flow cytometry and immunohistochemistry (IHC) in select cell lines. Total RNA was isolated from 38 human osteosarcoma samples for qRT-PCR analysis. Clinical data were sorted and significance was determined by Student t-test. TILs were examined in patient samples by tissue microarray (TMA) hematoxylin-eosin (HE) staining. We confirmed the constitutive PD-L1 mRNA expression in cell lines by qRT-PCR, flow cytometry, and IHC. Across human osteosarcoma samples, PD-L1 mRNA gene expression ranged over four-log (>5000-fold difference). Relative expression levels were evaluated against clinical factors such as age/gender, metastasis, recurrence, chemotherapy, percent necrosis, and survival; no significant associations were identified. The presence of TILs was associated with high PD-L1 expression (R2=0.37, P=0.01). In summary, we developed an RNA-based assay to determine PD-L1 expression levels, and we show for the first time that high levels of PD-L1 are expressed in a subset of osteosarcoma, and PD-L1 expression is positively correlated with TILs. There are multiple agents targeting PD-1/PD-L1 in clinical development, and this may be a novel immunotherapeutic strategy for osteosarcoma clinical trials.

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“…The material and methods of placenta TMA were provided in our previous study [13]. In this study, placenta TMA was used to detect the expression of HMGB1 and RAGE in patients with severe PE and normal controls.…”

Section: Immunohistochemistry In Placental Tissue Microarraymentioning

confidence: 99%