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p53 unterdrückt die Bildung von Typ-II-Endometriumkarzinomen im Mausmodell und ist ein unabhängiger negativer Prognosefaktor bei Patientinnen mit Endometriumkarzinom


Wild, P J (2013). p53 unterdrückt die Bildung von Typ-II-Endometriumkarzinomen im Mausmodell und ist ein unabhängiger negativer Prognosefaktor bei Patientinnen mit Endometriumkarzinom. In: 97. Jahrestagung der Deutschen Gesellschaft für Pathologie, Heidelberg, 23 May 2013 - 26 May 2013, 180-188.

Abstract

Type II endometrial carcinomas are a highly aggressive group of tumor subtypes that are frequently associated with inactivation of the TP53 tumor suppressor gene. We show that mice with endometrium-specific deletion of the Trp53 gene initially exhibited histological changes that are identical to known precursor lesions of type II endometrial carcinomas in humans and later developed carcinomas representing all type II subtypes. The mTORC1 signalling pathway was frequently activated in these precursor lesions and tumors, suggesting a genetic cooperation between this pathway and Trp53 deficiency in tumor initiation. Consistent with this idea, analyses of 521 human endometrial carcinomas identified frequent mTORC1 pathway activation in type I as well as type II endometrial carcinoma subtypes. The mTORC1 pathway activation and p53 expression or mutation status each independently predicted poor patient survival. We suggest that molecular alterations in p53 and the mTORC1 pathway play different roles in the initiation of the different endometrial cancer subtypes but combined p53 inactivation and mTORC1 pathway activation are unifying pathogenic features among histologically diverse subtypes of late stage aggressive endometrial tumors.

Abstract

Type II endometrial carcinomas are a highly aggressive group of tumor subtypes that are frequently associated with inactivation of the TP53 tumor suppressor gene. We show that mice with endometrium-specific deletion of the Trp53 gene initially exhibited histological changes that are identical to known precursor lesions of type II endometrial carcinomas in humans and later developed carcinomas representing all type II subtypes. The mTORC1 signalling pathway was frequently activated in these precursor lesions and tumors, suggesting a genetic cooperation between this pathway and Trp53 deficiency in tumor initiation. Consistent with this idea, analyses of 521 human endometrial carcinomas identified frequent mTORC1 pathway activation in type I as well as type II endometrial carcinoma subtypes. The mTORC1 pathway activation and p53 expression or mutation status each independently predicted poor patient survival. We suggest that molecular alterations in p53 and the mTORC1 pathway play different roles in the initiation of the different endometrial cancer subtypes but combined p53 inactivation and mTORC1 pathway activation are unifying pathogenic features among histologically diverse subtypes of late stage aggressive endometrial tumors.

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Additional indexing

Other titles:p53 suppresses type II endometrial carcinomas in mice and governs endometrial tumor aggressiveness in humans
Item Type:Conference or Workshop Item (Speech), refereed, further contribution
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
Dewey Decimal Classification:610 Medicine & health
Language:German
Event End Date:26 May 2013
Deposited On:07 Jan 2014 15:35
Last Modified:07 Aug 2017 07:04
Publisher:Springer
Series Name:Der Pathologe
Number:34/2
ISSN:0172-8113
Publisher DOI:https://doi.org/10.1007/s00292-013-1859-x
PubMed ID:24196610

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