BackgroundRenal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE3 gene fusion is a rare and new subtype of RCC and was classified by the WHO in 2004. Since then, multiple 5′ fusion partners for TFE3 have been reported; however, the impact of individual fusion variant on specific clinicopathologic features of Xp11.2 RCCs has not been well defined.MethodsFour Xp11.2 translocation RCCs were identified by morphological, immunostaining, and fluorescence in situ hybridization (FISH) assays from 200 patients who attended Guangdong General Hospital between January 2017 and January 2020. All these four cases were further analyzed by RNA sequencing to explore their TFE3 gene fusion partners. The clinicopathologic features, including clinical manifestations, pathological findings, treatment strategies, clinical outcomes, and follow-up information on Xp11.2 translocation RCCs, were recorded and evaluated.ResultsThese four cases affected one male and three females. The median age was 13 years at the time of diagnosis (range = 4–20 years). All the examined tumors were unilateral and unifocal. The largest diameter of these tumors ranged from 2.0 to 10.0 cm, and the average was 5.55 cm. Regional lymph node or distant metastasis developed in two patients. Three cases demonstrated known fusions: ASPCR1–TFE3 (two cases) and PRCC–TFE3 (one case). However, one case showed an unreported VCP–TFE3 fusion gene in Xp11.2 translocation RCCs. Immunohistochemistry results revealed tumor cells diffusely positive for TFE3, but have no consistency in other markers. Moreover, there were different clinical prognoses among the different variant TFE3 rearrangements; RCC patients with VCP–TFE3 translocation had worse prognosis compared to those with other fusion types. Follow-up were available for all the patients and ranged from 3 to 36 months. Three patients were without evidence of disease progression, while that with VCP–TFE3 fusion died of the disease 3 months after the diagnosis.ConclusionIn conclusion, our data expand the list of TFE3 gene fusion partners and the clinicopathologic features of Xp11.2 RCCs with specific TFE3 gene fusions. We identified a novel VCP–TFE3 fusion in Xp11.2 translocation RCCs for the first time, which has unique morphology and worse prognosis than those with other variant TFE3 rearrangements. Integration of morphological, immunohistochemical, and molecular methods is often necessary for the precise diagnosis and optimal clinical management of malignant tumors.
MicroRNAs (miRNAs) have been confirmed to play pivotal roles in hepatocellular carcinoma (HCC) carcinogenesis. However, the underlying function of microRNA-33b (miR-33b) in HCC remains unclear. Here, we found that miR-33b level was significantly reduced in both HCC tissues and tumor cell lines. Further, luciferase reporter assay and western blot analysis confirmed that Friend leukemia virus integration 1 (Fli-1) was a direct target of miR-33b. Overexpression of miR-33b dramatically suppressed HCC tumor cell proliferation and cell mobility, but facilitated tumor cell apoptosis in vitro.Besides, restoration of Fli-1 partially attenuated miR-33b-mediated inhibition of cell growth and metastasis via activating Notch1 signaling and its downstream effectors.Our findings demonstrate the important role of miR-33b/Fli-1 axis in HCC progression and provide novel therapeutic candidates for HCC clinical treatment.
Background: Programmed death-ligand 1 (PD-L1) expression in non-small cell lung cancer (NSCLC) is considered as a predictive biomarker of anti-PD-1/PD-L1 cancer therapies. However, the correlation of PD-L1 expression status between the primary and paired metastatic NSCLC is still not clear. The current study aims to address this specific issue. Materials and Methods: The PD-L1 expression of the primary and paired metastatic lesions from 110 patients with NSCLC was retrospectively evaluated by immunohistochemical assay using Anti-PD-L1 antibody, Clone 22C3. The results were assessed by the Tumor Proportion Score (TPS) using cutoff values of <1%, 1%-49% and ≥50%. Meanwhile, the Cohen's kappa coefficient (k) of agreement was calculated. Results: An overall concordance rate of the PD-L1 expression between the primary and metastatic lesions was 61% (63/103) (k = 0.39, and P < 0.001). If using TPS considering 1% and 50% as a threshold, the inconsistent rate was 28/103 (27.2%) paired specimens (k = 0.46, and P < 0.001) and 14/103 (13.6%) paired specimens (k = 0.53, and P < 0.001), respectively. Moreover, the concordance of the PD-L1 expression between primary and metastatic tumor was also analyzed according to the clinical stages within the untreated group of patients. We observed that for patients with stage I-III NSCLC, the concordance rate of the PD-L1 expression between primary and metastatic lesions was 81.3% and 100% when using 1% and 50% as threshold, respectively. While in stage IV patients, the concordance rate of the PD-L1 expression between the primary and metastatic lesions drops to 71.4% and 85.7%, respectively. Conclusion: The PD-L1 expression was dynamic as tumor developed, which was valuable in selecting the proper type of sample for accurately evaluating the prognosis of using pembrolizumab as first or second line treatment.
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