747 IS 99MTC BONE SCINTIGRAPHY NECESSARY IN THE PREOPERATIVE WORKUP FOR PATIENTS WITH POTENTIALLY RESECTABLE ESOPHAGEAL SQUAMOUS CELL CANCER?

99mTc bone scintigraphy(BS) is still the most widely used method to evaluate bone metastasis in China. The aim of this study was to investigate the necessity of the 99mTc bone scintigraphy in the preoperative workup for patients with potentially resectable esophageal squamous cell cancer (ESCC,cT1-4aN0–3). Methods This was a prospective cross-section clinical trial (ChiCTR1800020304). There were a total of 471 patients who were diagnosed ESCC in Thoracic Surgery Clinic from October 2018 to September 2020. Of these 471 patients, 385 patients with cT1-4aN0–3 who were potentially candidates for surgical resection were consecutively enrolled into the study. BS was performed preoperatively. The treatment strategy could be changed if the bone metastasis was confirmed. The primary endpoint was the incidence rate of the treatment regimen being changed because of bone metastasis. The secondary endpoint was the rate of positive BS findings. Results In all 385 patients, there are only 2(0.5%) patients changed their treatment regimen because of bone metastasis proved by BS. The rate of positive BS findings is 1%. The number of patients with false positive and false negative was 2(0.5%) and 2 (0.5%), respectively. The BS diagnostic performance for bone metastasis was as follows: sensitivity, 50%; specificity, 99.5%; positive predictive value, 50%; negative predictive value, 99.5% and accuracy, 99.0%. There were no significant difference of bone metastasis among the Age, Sex, Tumor location and Clinical stage. Conclusion 99mTc bone scintigraphy is unnecessary in the preoperative workup for patients with potentially resectable esophageal squamous cell cancer.

547 THE ROLE OF HEAT SHOCK PROTEIN 90 IN HYPOXIA INDUCED ANGIOGENESIS AND EPITHELIAL-MESENCHYMAL TRANSITION OF ESOPHAGEAL SQUAMOUS CELL CANCER

Hypoxia is known as an important trigger for the development of metastases in human cancers. Heat shock proteins (Hsps) are up-regulated by cellular stressors including hypoxia. To date, the functional role of Hsps within the hypoxic tumor microenvironment for esophageal squamous cell cancer (ESCC) remains poorly defined. Methods CoCl₂ was used to induce hypoxia in cultured ESCC cells which was confirmed by 2′,7′ –dichlorofluorescin diacetate (DCFDA) assay. 7-Dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), a selective Hsp90 inhibitor, was used to treat 2 ESCC cell lines, KYSE-170 and -510 cells pretreated with or without CoCl₂₂₂₂₂ in different concentrations, followed by cytotoxicity (MTT) and migration assays. In parallel, expression of Hsp90, vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1α (HIF-1α), and markers related to epithelial-mesenchymal transition (EMT) such as snail/E-cadherin, by immunoblot or ELISA while analyzing cell proliferation and migration of treated ESCC cells. Results CoCl₂ induced hypoxia was supported by induction of reactive oxygen species (ROS). CoCl₂ (200 μM) significantly suppressed cell viability and proliferation with a concomitant up-regulation of VEGF and HIF-1α in a dose-dependent fashion. In contrast, cell migration was significantly increased in response to CoCl₂ while down-regulating E-cadherin with a concomitant increase in Snail expression. 17-DMAG decreased expression of VEGF and HIF-1α while inhibiting cell migration and invasion. Conclusion Our data demonstrate that CoCl2 induced hypoxia promotes EMT and angiogensis, which are inhibited by 17-DMAG. These results suggest that hypoxia induced EMT and angiogensis is Hsp90 dependent in ESCC.