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Journal Thoracic Oncology

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Abstracts <strong>Journal</strong> of <strong>Thoracic</strong> <strong>Oncology</strong> • Volume 12 Issue S1 January 2017<br />

MAPK pathways resulted in the opposite regulation of these genes. Inhibition<br />

of MMP1 via siRNAs or pharmacological inhibitors prevented FGF2-induced<br />

scattering and invasiveness. In unsupervised clustering, the gene expression<br />

profiles of solvent- or cytokine-treated cells were associated with those of<br />

epithelioid and sarcomatoid MPM, respectively. Immunohistochemistry<br />

showed an association of MMP1 as well as phospho-ERK with the sarcomatoid<br />

part of tissue specimens from biphasic tumors. Pathway enrichment analysis<br />

of differentially expressed genes as well as the targets of altered microRNAs<br />

after FGF2 treatment showed that the regulated genes are assigned to<br />

categories important for cell growth and aggressive behavior. Conclusion:<br />

Our data characterize FGFR-mediated signals as important players in<br />

MPM aggressiveness and the morphological and behavioral plasticity of<br />

mesothelioma cells, leading to a better understanding of the link between the<br />

MPM histological subtypes and their influence on patient outcome.<br />

Keywords: Epidermal Mesenchymal Transition, Mesothelioma, Fibroblast<br />

Growth Factors<br />

POSTER SESSION 3 – P3.03: MESOTHELIOMA/THYMIC MALIGNANCIES/ESOPHAGEAL<br />

CANCER/OTHER THORACIC<br />

MESOTHELIOMA TRANSITIONAL –<br />

WEDNESDAY, DECEMBER 7, 2016<br />

P3.03-003 MESOTHELIUM COVERING PLEURAL PLAQUE IS NOT<br />

PRIMARILY INVOLVED IN ASBESTOS-INDUCED MESOTHELIAL<br />

CARCINOGENESIS IN HUMAN<br />

Yuichi Koda, Kozo Kuribayashi, Shingo Kanemura, Eisuke Shibata, Taiichiro<br />

Otsuki, Koji Mikami, Takashi Nakano<br />

Respiratory, Nishinomiya/Japan<br />

Background: Malignant pleural mesothelioma (MPM) initially arises not<br />

from the visceral pleura but parietal pleural mesothelial cells in the thoracic<br />

cavity. MPM has a close relationship to asbestos exposure in etiology. The<br />

carcinogenic potential of asbestos fibers has been linked to their geometry,<br />

size, and chemical composition. Long respirable fibers(length>5μm,<br />

diameter5% membranous staining regardless of intensity and<br />

high positive as >50%. Genomic DNA was obtained from tumour cores of a<br />

representative subset (100 patients) and used for genome-wide copy number<br />

analysis. Percent genome aberrated (PGA) was computed for each sample<br />

as the total number of base pairs within altered regions, divided by the total<br />

number of base pairs in each region included in the array. Correlations of PGA,<br />

CNA profile and individual aberration (loss/gain) frequency with parameters<br />

including PD-L1 expression and survival were explored. Results: Amongst<br />

329 patients evaluated, the median age was 67 years and most were male<br />

274(83.2%). Epithelioid histology (N=203; 62.9%) was the commonest. PD-L1<br />

positivity was seen in 41.7% with high positivity in 9.6%. PD-L1+ correlated<br />

with non–epitheloid histology (P=

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