Intra-Abdominal Epithelioid Neoplasm With EWSR1::CREB Fusions Involving the Kidney: A Clinicopathologic and Molecular Characterization With an Emphasis on Differential Diagnosis.

Soft tissue neoplasms, harboring fusions between EWSR1 and FUS with genes encoding CREB transcription factors family (ATF1, CREB1, and CREM), are an emerging heterogeneous group of mesenchymal tumors that differ significantly in morphology, immunophenotypes, and behavior. Recently, EWSR1/FUS::CREB fusions have been recognized to define a group of aggressive neoplasms of epithelioid morphology with multiple growth patterns and a striking predilection for mesothelial-lined cavities. These neoplasms presenting as a primary neoplasm of intra-abdominal visceral organs are rare, which could elicit a wide range of differential diagnoses because of their diverse morphologies and immunohistochemical profiles. We report 3 cases of intra-abdominal epithelioid neoplasms with EWSR1::CREB fusions involving the kidney. This study included 2 female patients and 1 male patient, with age at presentation ranging from 17 to 61 years (mean: 32 years). All the patients underwent radical nephrectomy without adjunctive therapies. Grossly, the tumors were large, and all were solitary masses with sizes ranging from 5.6 to 30.0 cm (mean: 14.5 cm). Histologically, the neoplasms showed infiltrating and indistinct borders and were composed predominantly of monomorphic round-to-epithelioid cells with variable amounts of pale-to-clear cytoplasm, arranged in cords, nests, and sheets and embedded in a sclerotic hyalinized stroma with variable lymphoid cuffing either intermixed or at the periphery. Notably, a hemangiopericytomatous growth pattern was commonly seen. Nuclear atypia was mild, and mitotic activity was scarce. Immunohistochemically, all 3 cases were at least focally positive for epithelial membrane antigen and keratin AE1/AE3, with 2 tumors showing focal MUC4 expression and 1 case displaying diffuse CD34 and focal CAIX positivity. Targeted RNA sequencing identified EWSR1::CREM fusion in 2 cases and EWSR1::ATF1 fusion in 1 case. Subsequent fluorescence in situ hybridization analysis confirmed the RNA sequencing results. On follow-up, 1 patient developed multiple spinal bone metastases 5 months after the surgery while the other 2 patients were free of disease 9 and 120 months after diagnosis, respectively. Our findings demonstrate that intra-abdominal epithelioid neoplasms with EWSR1::CREB fusions may rarely occur primarily in the kidney and should be included in the differential diagnosis of primary renal epithelioid mesenchymal neoplasms.

Temporal trends and barriers for inpatient palliative care referral in metastatic gynecologic cancer patients receiving specific critical care therapies.

Objective: Existing evidence suggests that palliative care (PC) is highly underutilized in metastatic gynecologic cancer (mGCa). This study aims to explore temporal trends and predictors for inpatient PC referral in mGCa patients who received specific critical care therapies (CCT). Methods: The National Inpatient Sample from 2003 to 2015 was used to identify mGCa patients receiving CCT. Basic characteristics were compared between patients with and without PC. Annual percentage change (APC) was estimated to reflect the temporal trend in the entire cohort and subgroups. Multivariable logistic regression was employed to explore potential predictors of inpatient PC referral. Results: In total, 122,981 mGCa patients were identified, of whom 10,380 received CCT. Among these, 1,208 (11.64%) received inpatient PC. Overall, the rate of PC referral increased from 1.81% in 2003 to 26.30% in 2015 (APC: 29.08%). A higher increase in PC usage was found in white patients (APC: 30.81%), medium-sized hospitals (APC: 31.43%), the Midwest region (APC: 33.84%), and among patients with ovarian cancer (APC: 31.35%). Multivariable analysis suggested that medium bedsize, large bedsize, Midwest region, West region, uterine cancer and cervical cancer were related to increased PC use, while metastatic sites from lymph nodes and genital organs were related to lower PC referral. Conclusion: Further studies are warranted to better illustrate the barriers for PC and finally improve the delivery of optimal end-of-life care for mGCa patients who receive inpatient CCT, especially for those diagnosed with ovarian cancer or admitted to small scale and Northeast hospitals.

Extracellular vesicle-derived circHIPK3: Novel diagnostic biomarker for lung cancer.

PURPOSE: Lung cancer (LC) is a common malignancy worldwide. A great number of circular RNAs (circRNAs) have been identified that serve crucial roles in cancer development. Extracellular vesicles (EVs) and their contents have been shown to be biomarkers for the diagnosis and prognosis of LC. Thus, we intended to clarify the functional role of EVs-derived circRNA homology domain interacting protein kinase 3 (EVs-circHIPK3) and its underlying mechanism of action. MATERIAL AND METHODS: Bioinformatics analysis was performed to validate the potential of partially circulating HIPK3 in LC diagnosis. EVs were isolated by polyethylene glycol (PEG) precipitation from plasma of 52 LC patients and 30 healthy controls. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was employed to evaluate the expressions of candidate circRNAs (circHIPK3) and microRNA-637 (miR-637, a target of circHIPK3). RESULTS: CircHIPK3 is significantly up-regulated in LC, while miR-637 expression is significantly reduced (p â€‹< â€‹0.05). Receiver operating characteristic (ROC) curve analysis, based on the expression of EVs-circHIPK3, allowed us to distinguish LC from healthy controls (area under the curve, AUC 0.897). CONCLUSIONS: Taken together, our study shows that EV-derived circHIPK3 can serve as a promising biomarker for LC patient diagnosis. However, the downstream mRNA of the circHIPK3/miR-637 axis requires further exploration to enrich our understanding of circHIPK3's mechanism in LC.

Elevated epiregulin expression predicts poor prognosis in gastric cancer.

Epiregulin (EREG) is a novel family member of EGF-like ligands and have elevated expression in a variety of human cancers. EREG expression promotes tumor progression and metastasis and reduces patient survival. However, the expression of EREG and its prognostic value are not clear in gastric cancer (GC). We assessed EREG mRNA and protein expression in GC tissues from Chinese patients using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical staining of tissue microarray, and analyzed the correlation between the level of EREG expression and patient clinical characteristics and prognosis. We found that EREG expression was significantly higher in GC tissues than in matched adjacent noncancerous tissues. High EREG protein expression in GC was significantly associated with TNM stage including tumor size, lymph node metastases and distant metastases as well as poor overall survival. These finding demonstrate that EREG is an independent prognostic biomarker for GC.