Somma, Anna (2017) Craniopharyngiomas: immunohistochemical evaluation of prognostic factors. [Tesi di dottorato]

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Item Type: Tesi di dottorato
Lingua: English
Title: Craniopharyngiomas: immunohistochemical evaluation of prognostic factors
Creators:
CreatorsEmail
Somma, Annasommaanna79@gmail.com
Date: 2017
Number of Pages: 44
Institution: Università degli Studi di Napoli Federico II
Department: Scienze Biomediche Avanzate
Dottorato: Scienze biomorfologiche e chirurgiche
Ciclo di dottorato: 29
Coordinatore del Corso di dottorato:
nomeemail
cuocolo, albertocuocolo@unina.it
Tutor:
nomeemail
De Rosa, GaetanoUNSPECIFIED
Date: 2017
Number of Pages: 44
Uncontrolled Keywords: CP, B-catenin
Settori scientifico-disciplinari del MIUR: Area 06 - Scienze mediche > MED/08 - Anatomia patologica
Date Deposited: 18 Apr 2017 11:50
Last Modified: 14 Mar 2018 09:50
URI: http://www.fedoa.unina.it/id/eprint/11778
DOI: 10.6093/UNINA/FEDOA/11778

Abstract

Craniopharyngiomas (CPs) are a heterogeneous group of benign but locally aggressive epithelial tumors arising within the sellar region, along the path of craniopharyngeal duct. The CPs are benign neoplasms, histologically grade I sec WHO (2007), of which there are two subtypes: the adamantinomatous (adaCP), which is the most frequent and the papillary (papCP), rarer. The two subtypes differ in terms of frequency, age distribution, morphological and biological aspects and also show a different prognosis and clinical outcome. The exact etiopathogenesis of these tumors is still unclear and highly controversial, however, several genetic and molecular aspects seem to indicate a distinct pathogenesis in two subtypes: the papCP originates from the metaplastic transformation of mature epithelial cells of the anterior pituitary, the adaCP derives from less differentiated cells of Rathke's pouch, left over along the course of craniopharyngeal duct. In this process plays a fundamental role the Wnt pathway / beta-catenin (canonical WNT pathway). CTNNB1 mutations of the gene encoding the beta-catenin in exon 3 involve deletions or substitutions of amino acid residues critical for its degradation by the destruction of the complex causing, therefore, an increase in cytoplasmic levels of the protein, its expression aberrant nuclear and, consequently, a constitutive activation of the Wnt pathway. Mutations of the gene CTNNB1 therefore constitute the molecular hallmark of adaCP, however, the nuclear expression of β-catenin is observed only in small clusters of neoplastic cells; these clusters often show a "whirl-like" morphology and are exclusively observed in adaCP, never in papCP or other tumors of the sellar region. Recent studies, both mouse models and in human tumors, have investigated the presence of cancer stem cells in pituitary tumors, especially in adaCP. The results of these studies suggest that the adaCP presented a minority population of cells with stem cell phenotype. These clusters are characterized by the expression of aberrant nuclear beta-catenin. ATM (ataxia-telangiectasia-mutated) is a known tumour suppressor which is frequently mutated in a broad range of human cancers including lung, colorectal, breast and haematopoietic cancers. .ATM was first described in 1995 as the gene defective in the autosomal recessive human hereditary disorder ataxia–telangiectasia (A–T). This disease, caused by a loss of ATM function, is characterized by progressive cerebellar degeneration, telangiectasia, immunodeficiency, genomic instability cancer susceptibility and profound sensitivity to ionising radiation (IR); this hypersensitivity of ATM-defective cells to IR represents the main interest for ATM as therapeutic target for cancer therapy. We analyzed a collection of 45 samples of craniopharyngiomas, comprising 38 cases of adaCP and 7 cases of papCP. Therefore 13 cases were considered recurrent and 32 not recurrent. For each case we obtained sections for immunohistochemical evaluation of beta-catenin, CD166, CD133, Ki67 e pATM. The results obtained were correlated with the clinical aspects of CPs, or the presence or absence of tumor recurrence. The purpose of this study was to obtain a marker panel to identify tumors with more aggressive biological behavior, therefore defining a more appropriate treatment strategy, with post-operative additional treatments.

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