Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04155 (pS2)
 1,234 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

On the basis of morphological features, we subclassified 189 intrahepatic cholangiocarcinomas into two subtypes: bile duct and cholangiolar. The cholangiolar type is composed of cuboidal to low columnar tumor cells that contain scanty cytoplasm. The bile duct type is composed of tall columnar tumor cells arranged in a large glandular pattern. In this study, 77 (41%) tumors were classified as the cholangiolar type and 112 (59%) tumors were classified as the bile duct type. The cholangiolar-type intrahepatic cholangiocarcinoma was more frequently associated with viral hepatitis, whereas all but one intrahepatic cholangiocarcinoma associated with intrahepatic lithiasis were classified as the bile duct type. Biliary intraepithelial neoplasm or intraductal papillary neoplasm of the bile duct could be identified in 50 bile duct-type intrahepatic cholangiocarcinomas (45%), but in only 3 cholangiolar-type intrahepatic cholangiocarcinomas (4%). Cholangiolar-type intrahepatic cholangiocarcinomas frequently expressed N-cadherin, whereas bile duct intrahepatic cholangiocarcinomas were more likely to express S100P, Trefoil factor 1, and anterior gradient 2. KRAS is mutated in 23 of 98 (23%) bile duct-type intrahepatic cholangiocarcinomas and in only 1 of 76 (1%) cholangiolar-type intrahepatic cholangiocarcinomas. Cholangiolar-type intrahepatic cholangiocarcinomas had a higher frequency of IDH1 or 2 mutations than did the bile duct-type intrahepatic cholangiocarcinomas. The molecular features of the bile duct-type intrahepatic cholangiocarcinoma were similar to those of hilar cholangiocarcinoma. Patients with the cholangiolar-type intrahepatic cholangiocarcinoma had higher 5-year survival rates than those of patients with the bile duct-type intrahepatic cholangiocarcinoma. Our results indicated that intrahepatic cholangiocarcinoma was a heterogeneous tumor. Subclassification of intrahepatic cholangiocarcinomas based on cholangiocytic differentiation divides them into two groups with different etiologies, clinical manifestations, and molecular pathogeneses.
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PMID:Morphological subclassification of intrahepatic cholangiocarcinoma: etiological, clinicopathological, and molecular features. 2440 66

Metastatic breast cancer is one of the leading causes of cancer related death in women. Limited studies have been done on the genomic evolution between primary and metastatic breast cancer. We reconstructed the genomic evolution through the sixteen year history of an ER+ HER2- breast cancer patient to investigate molecular mechanisms of disease relapse and treatment resistance after long term exposure to hormonal therapy. Genomic and transcriptome profiling was performed on primary breast tumor (2002), initial recurrence (2012) and liver metastasis (2015) samples. Cell free DNA analysis was performed at eleven timepoints (2015-2017). Mutational analysis revealed a low mutational burden in the primary tumor which doubled at the time of progression, with driver mutations in PI3K-Akt and RAS-RAF signaling pathways. Phylogenetic analysis showed an early branching off between primary tumor and metastasis. Liquid biopsies, while initially negative, started to detect an ESR1 E380Q mutation in 2016 with increasing allele frequency till end of 2017. Transcriptome analysis revealed 721 (193 up, 528 down) genes to be differentially expressed between primary tumor and first relapse. Most significantly down-regulated genes were TFF1 and PGR, indicating resistance to AI therapy. Most up-regulated genes included PTHLH, S100P, and SOX2 promoting tumor growth and metastasis. This phylogenetic reconstruction of the life history of a single patient's cancer as well as monitoring tumor progression through liquid biopsies allowed for uncovering the molecular mechanisms leading to initial relapse, metastatic spread and treatment resistance.
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PMID:Case Report - 16 Year Life History and Genomic Evolution of an ER+ HER2- Breast Cancer. 3300 33