Catenin-beta (Phospho-Tyr489) ELISA Kit

AimsPleomorphic adenoma gene 1 (PLAG1) rearrangement is well known in pleomorphic adenoma (PA), which is histologically characterised by admixed epithelial and mesenchymal components. Multiple fusion variants of PLAG1 and HMGA2 have been reported; currently, however, little is known regarding the clinicopathological impacts of these fusion types Methods and resultsWe examined the PLAG1- and HMGA2-related fusion status in 105 PAs and 11 cases of carcinoma ex PAs (CXPA) arising from salivary glands and lacrimal glands to elucidate their correlation to the clinicopathological factors. Forty cases harboured PLAG1 fusion genes: CTNNB1-PLAG1 in 22 cases, CHCHD7-PLAG1 in 14 cases and LIFR-PLAG1 in four cases. Only two cases possessed HMGA2 fusion genes. The mean age of LIFR-PLAG1-positive cases was significantly higher than that of CTNNB1-PLAG1- and CHCHD7-PLAG1-positive cases (P=0.0358). PAs located in the submandibular gland demonstrated CTNNB1-PLAG1 fusion at a significantly higher rate than other fusions (P=0.0109). Histologically, PLAG1 fusion-positive cases exhibited chondroid formation and plasmacytoid features more commonly (P=0.043, P=0.015, respectively) and myxoid abundant feature less frequently (P=0.031) than PLAG1 fusion-negative cases. For CXPAs, four CTNNB1-PLAG1 fusions were detected in two salivary duct carcinomas and two myoepithelial carcinomas. Ductal formation was observed frequently (90.9%) in residual PA. ConclusionsThe presence of PLAG1 fusion was associated with specific histological features in PA. Detecting the PLAG1 fusion gene and searching residual ductal formation in salivary gland malignant tumours with extensive hyalinisation could be useful for diagnosis.

Patients with prostate cancer with tumors harboring defects in DNA-repair genes (DRD) generally do not respond well to AR-directed therapy. Furthermore, canonical pathways evolve during disease progression and may affect treatment with existing therapies. Due to the limited treatment options after failure of hormonal and taxane therapy, and the tumor heterogeneity induced by DRD, we sought to characterize the alterations in primary and metastatic prostate cancer. Tumors from 1,027 patients with advanced prostate cancer that underwent comprehensive genomic profiling for routine clinical care were reviewed to assess DRD mutation rates (27-gene panel) and co-occurring mutations in select canonical prostate cancer pathways. DRD alterations were identified in 20 genes and in 17% of patients (BRCA2 and ATM most common) occurring with slightly higher frequency in specimens from metastatic biopsy sites and men older than 50 years of age. Microsatellite instability-high (MSI-H) and tumor mutational burden-high occurred with 3% frequency in the overall cohort but were not enriched in metastatic disease. Biomarkers previously associated with antitumor immunity are found at high frequencies in MSI-H patients, including JAK1 (68%) and PTEN (32%). Lastly, mutations in TP53, AR, PTEN, APC, CTNNB1, and PIK3CA were all significantly enriched in metastatic samples. We identified clinically significant subgroups of patients demonstrating (1) defects in DNA-repair pathways, (2) intrinsic prostate cancer signaling pathways that may prevent antitumor immunity, and (3) distinct genomic differences between localized and metastatic prostate cancer. These results lend support that genomic profiling for advanced prostate cancer may identify actionable targets not routinely used in the current metastatic paradigm.