Cytokeratin 7/19 expression inN-diethylnitrosamine-induced mouse hepatocellular lesions: implications for histogenesis International

• Type: Article in International Scientific Journal
• Date: 2014

Authors

Nuno P. Santos (Author) Other; Paula A. Oliveira (Author) Other; Regina Arantes Rodrigues (Author) Other; Ana I. Faustino Rocha (Author) Other; Aura Colaço (Author) Other; Carlos Lopes (Author) Other; Rui M. Gil da Costa (Author) FEUP

Journal

Title: International Journal of Experimental Pathology

Vol. 95 No. 3

Pages: 191-198

ISSN: 0959-9673

Publisher: Wiley-Blackwell

Indexing

ISI Web of Science

Scopus

Associated Projects

UI0511 - PROJECTO ESTRATÉGICO - UI 511 - 2013-2014

Other information

DOI: 10.1111/iep.12082

Abstract (EN): Hepatocellular carcinoma (HCC) is a common malignancy with poor clinical outcome, whose histogenesis is the subject of intense debate. Specifically, expression of cytokeratins (CKs) 7 and 19, associated with aggressive biological behaviour, is proposed to reflect a possible progenitor cell origin or tumour dedifferentiation towards a primitive phenotype. This work addresses that problem by studying CKs 7 and 19 expression in N-diethylnitrosamine (DEN)-induced mouse HCCs. ICR mice were divided into six DEN-exposed and six matched control groups. Samples were taken from each group at consecutive time points. Hyperplastic foci (13 lesions) occurred at 29–40 weeks (groups 8, 10 and 12) with diffuse dysplastic areas (19 lesions) and with one hepatocellular adenoma (HCA) (at 29 weeks). HCCs (4 lesions) were observed 40 weeks after the first DEN administration (group 12). CKs 7 and 19 showed identical expression patterns and located to large, mature hepatocytes, isolated or in small clusters. Hyperplastic foci and the single HCA were consistently negative for both markers, while dysplastic areas and HCCs were positive. These results support the hypothesis that CKs 7 and 19 expression in hepatocellular malignancies results from a dedifferentiation process rather than from a possible progenitor cell origin.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8