Anti-CTNNB1 (mutation S45Y) Monoclonal Antibody, clone XH031

The diagnosis of primary adenocarcinoma of the urinary bladder may be challenging in routine practice. These tumors may morphologically and immunohistochemically overlap with urachal adenocarcinoma and colorectal adenocarcinoma. Further, their genetic background is poorly understood. We systematically searched the PubMed database for results of complex genetic evaluation of primary bladder adenocarcinoma subtypes. Subsequently, we designed our own series of bladder lesions. We evaluated 36 cases: 16 primary enteric-type adenocarcinomas, 7 urachal enteric adenocarcinomas, 3 primary mucinous/colloid adenocarcinomas, and 10 intestinal-type metaplasia/villous adenoma. Detailed clinical data were collected, and all cases were examined using targeted next-generation sequencing. On the basis of the literature, the first mutated gene in these tumors was reported to beKRASin 11.3% of cases, followed byTERTpromoter mutations in 28.5%. In addition toKRASandTERT, other genes were also found to be frequently mutated in primary bladder adenocarcinoma, includingTP53,PIK3CA,CTNNB1,APC,FBXW7,IDH2, andRB1. In our series, the most frequent gene mutations in primary enteric-type adenocarcinomas were as follows:TP53(56%);BRCA2,KMT2B(both 33%);NOTCH2,KDR,ARID1B,POLE,PTEN,KRAS(all 28%); in urachal enteric adenocarcinoma they were as follows:TP53(86%);PTEN,NOTCH(both 43%); in primary mucinous/colloid adenocarcinomas they were as follows:KRAS,GRIN2A,AURKB(all 67%); and, in intestinal-type metaplasia/villous adenoma, they were as follows:APC,PRKDC(both 60%);ROS1,ATM,KMT2D(all 50%). No specific mutational pattern was identified using cluster analysis for any of the groups. Herein, we describe the pathologic features and immunohistochemical staining patterns traditionally used in the differential diagnoses of glandular lesions of the bladder in routine surgical pathology. We outline the mutational landscape of these lesions as an aggregate of published data with additional data from our cohort. Although diagnostically not discriminatory, we document that the most common genetic alterations shared between these glandular neoplasms includeTP53,APC(in the Wnt pathway), andKRAS(in the MAPK pathway) mutations.

Background: Colon cancer is the second leading cancer worldwide. Recurrent disease and chemotherapeutic drug resistance are very common in the advanced stage of colon cancer. ATP-citrate lyase (ACLY), the first-step rate-controlling enzyme in lipid synthesis, is elevated in colon cancer. However, it remains unclear about the exact role of ACLY in the development of colon cancer metastasis. Methods: To evaluate the role of ACLY in colon cancer metastasis, we performed cell migration and invasion assays in two ACLY-deficient colon cancer cell lines. Colon cancer mouse model is used to examine ACLY's effects on colon metastasis potentials in vivo. We analyzed the correlation between ACLY and CTNNB1 protein in 78 colon cancer patients by Pearson correlation. To finally explore the relationship of ACLY and CTNNB1, we used western blots, migration and invasion assays to confirm that ACLY may regulate metastasis by CTNNB1. Results: Our data showed that the abilities of cell migration and invasion were attenuated in ACLY-deficient HCT116 and RKO cell lines. Furthermore, we describe the mechanism of ACLY in promoting colon cancer metastasis in vitro and in vivo. ACLY could stabilize CTNNB1 (beta-catenin 1) protein by interacting, and the complex might promote CTNNB1 translocation through cytoplasm to nucleus, subsequently promote the CTNNB1 transcriptional activity and migration and invasion abilities of colon cancer cells. Immunohistochemical analysis of 78 colon cancer patients showed that the high expression levels of ACLY and CTNNB1 protein was positively correlated with metastasis of colon cancer. Conclusions: These results shed new light on the molecular mechanism underlying colon cancer metastasis, which might help in improving therapeutic efficacy.