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Cytokeratin 7/19 expression in N ‐diethylnitrosamine‐induced mouse hepatocellular lesions: implications for histogenesis
Author(s) -
Santos Nuno P.,
Oliveira Paula A.,
ArantesRodrigues Regina,
FaustinoRocha Ana I.,
Colaço Aura,
Lopes Carlos,
Gil da Costa Rui M.
Publication year - 2014
Publication title -
international journal of experimental pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.671
H-Index - 72
eISSN - 1365-2613
pISSN - 0959-9673
DOI - 10.1111/iep.12082
Subject(s) - histogenesis , cytokeratin , hepatocellular carcinoma , pathology , malignancy , phenotype , biology , progenitor cell , hepatocellular adenoma , immunohistochemistry , carcinogenesis , cancer research , medicine , stem cell , cancer , genetics , gene
Summary Hepatocellular carcinoma ( HCC ) is a common malignancy with poor clinical outcome, whose histogenesis is the subject of intense debate. Specifically, expression of cytokeratins ( CK s) 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 CK s 7 and 19 expression in N ‐diethylnitrosamine ( DEN )‐induced mouse HCC s. 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). HCC s (4 lesions) were observed 40 weeks after the first DEN administration (group 12). CK s 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 HCC s were positive. These results support the hypothesis that CK s 7 and 19 expression in hepatocellular malignancies results from a dedifferentiation process rather than from a possible progenitor cell origin.