Browsing by Subject "Molecular pathology"

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    From Barrett metaplasia to esophageal adenocarcinoma: the molecular background
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Saraggi, Deborah; Fassan, Matteo; Bornschein, Jan; Farinati, Fabio; Realdon, Stefano; Valeri, Nicola; Rugge, Massimo
    The molecular landscape of Barrett’s esophagus and Barrett-related neoplastic lesions is still far from being completely elucidated. Both in vitro and in vivo studies pinpointed the pathogenetic role of different morphogenic pathways (the para-homeobox, the Notch and the Sonic Hedgehog families in particular) implicated in the acquisition of the metaplastic phenotype of the esophageal mucosa. On the other hand, the most common genetic alterations observed during Barrett's carcinogenesis include disorders of major regulators of the cell cycle, as well as deregulation of the TGF-β/Smad and receptor tyrosine kinases signalling pathways. Recent comprehensive mutational profiling studies identified that the inactivation of the TP53 and of the SMAD4 tumour suppressor genes occurred in a stage-specific manner, confined to (high grade) dysplastic and neoplastic lesions, respectively. The next step will be the correlation of these findings into multidisciplinary diagnostic approaches integrating endoscopy, histology, molecular profiling and liquid biopsies. This will allow the introduction of innovative strategies for secondary prevention of esophageal adenocarcinoma based on biological rationales, and the implementation of potential novel therapeutic targets.
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    Molecular pathology of endometrial carcinoma, Transcriptional signature in endometrioid tumors
    (Murcia : F. Hernández, 2006) Abal, M.; Planaguma, J.; Gil-Moreno, A.; Monge, M.; Gonzalez, M.; Baró, Teresa; Garcia, A.; Castellvi, J.; Ramón y Cajal, S.; Xercavins, J.; Alameda, F.; Reventos, J.
    A dualistic model, which has been established on a morphological basis and that differentiates type I endometrioid from type II nonendometrioid endometrial cancer, is widely accepted. Molecular genetics have provided us with data supporting the dualistic model of endometrial tumorigenesis and with some clues to speculate about the sequence of the molecular alterations defining the tumorigenesis pathways. In type I endometrioid endometrial cancer, PTEN gene silencing, microsatellite instability associated with defects in DNA mismatch repair genes, or mutations in the K-ras gene are the known major alterations defining the progression from normal endometrium to hyperplasia and then on to carcinoma. Recently, cDNA microarray technology for identifying the differences in gene expression patterns between the histological types of endometrial cancer have permitted the identification of differentially expressed genes that could help us to understand differences in the biology and the clinical outcome between histiotypes. Genes involved in the mitotic checkpoint as a major mechanism of carcinogenesis in non-endometrioid endometrial cancer, or altered genes associated with the initial steps of myometrial infiltration in endometrioid endometrial cancer, represent examples of how useful large genetic screenings can be for understanding the tumorigenesis process and the future directions in the molecular pathogenesis of endometrial cancer.