Summary Tumor epithelial cells undergo a morphologic shift through the process of EMT with characteristic loss of cell polarity, conferring invasive and metastatic properties during cancer progression. Signaling by transforming growth factor-β mediates EMT programming and its phenotypic reversal to mesenchymal-epithelial transition. The role of EMT in bladder cancer progression to advanced disease is poorly understood. In this study, we conducted a retrospective analysis of the EMT landscape and actin cytoskeleton remodeling in a series of human bladder cancer specimens. Immunoreactivity for E-cadherin, N-cadherin, and vimentin protein expression was performed toward establishing an EMT signature in human bladder cancer. Serial sections were assessed for the primary regulator of the actin cytoskeleton remodeling and transforming growth factor-β signaling effector, cofilin. Our results demonstrate that EMT induction in clinical bladder cancer specimens is significantly associated with bladder cancer progression to high-grade, invasive disease. Evaluation of expression and cellular localization of the cytoskeleton regulator cofilin revealed a significant association between overexpression of nuclear cofilin with bladder cancer progression. This study is of translational significance in defining the value of EMT signature and cytoskeletal cofilin as potential tumor markers and targetable platforms for the treatment of invasive bladder cancer.

The acute complications of multiple myeloma can be varied and devastating, including electrolyte derangements, renal failure, and infections amongst others. The varying pathological mechanisms behind these complications make the management of patients presenting with multiple myeloma a complicated and sometimes tenuous process. The patient compliance can further exacerbate these difficulties. The patient discussed in this case initially presented with newly developed altered mental status, fatigue, epistaxis, and an ecchymotic rash. Laboratory testing and imaging would conclude a diagnosis of multiple myeloma, but unfortunately treatment was cut short. Admission at a later date would show rapidly deteriorating condition with new lung consolidations and worsening laboratory findings. Herein the authors discuss the clinical findings of patients with acute manifestations of multiple myeloma, their prognostic value, and the implications of patient compliance and early intervention in the setting of multiple myeloma.

e15087 Background: Venous thromboembolism (VTE) in patients with gastrointestinal (GI) and non‐small cell lung cancer (NSCLC) is common and increases morbidity and mortality. In advanced GI and NSCLC, molecular subtyping has increased use of next-generation sequencing (NGS). The association between tumor mutation profile and VTE risk remains undetermined. Methods: We conducted a retrospective cohort study of consecutive GI/NSCLC patients from 2014-2019 with NGS and follow‐up at Brown Cancer Center. The NGS platform detected substitutions, indels, copy number alterations and select rearrangements in 324 genes. Patients with thrombophilia, anticoagulation use or >1 malignancy were excluded. VTE was defined as deep vein thrombosis, pulmonary embolism or visceral vein thrombosis within 6 months prior to diagnosis or any time after. For statistical analysis SAS 9.5 was used with significance at alpha=0.05. Multinomial logistic regression was performed, in which the log odds of VTE was modeled as a linear combination of the genes. Odds ratios and 95% confidence intervals for VTE were generated. Results: A total of 364 patients were reviewed; after exclusions 326 patients were included comprising Stage III/IV NSCLC (58%), metastatic colorectal (33%) and other metastatic GI cancers - gastric, duodenal, esophageal, pancreatic and cholangiocarcinoma (9%). Approximately half (53%) were males with mean age of 59.1 yrs and 76.4% current/former smokers. There was a low level of microsatellite instability (0.9%). VTE occurred in 75 patients (23%) during a mean follow‐up of 24.5 months. Only 1 patient had surgery within 90 days prior to VTE. Of 248 genes mutated in the VTE group, 9 were more prevalent compared to those without VTE (Table). Statistical analysis showed PIK3CA, PTCH1, FGF6, and NRAS mutations significantly increased odds of VTE, with PIK3CA the most prevalent of these (Table). Conclusions: Patients with PIK3CA, PTCH1, FGF6 and NRAS mutations had significantly higher VTE risk. These tumor mutations and associated pathways may provide novel insight into risk stratification, prevention and targeted treatment of VTE in cancer. [Table: see text]