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Hypoxia after transarterial chemoembolization may trigger a progenitor cell phenotype in hepatocellular carcinoma
Author(s) -
Lai JinPing,
Conley Andrew,
Knudsen Beatrice S,
Guindi Maha
Publication year - 2015
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.12623
Subject(s) - hepatocellular carcinoma , cytokeratin , immunohistochemistry , pathology , progenitor cell , hypoxia (environmental) , medicine , carcinoma , cancer research , biology , stem cell , chemistry , organic chemistry , oxygen , genetics
Aims To test the hypothesis that the hypoxia marker carbonic anhydrase IX ( CAIX ), and the cholangiocytic/progenitor markers cytokeratin ( CK ) 19 and epithelial cell adhesion molecule (Ep CAM ), may be expressed in areas of hypoxia in hepatocellular carcinoma ( HCC ) after transarterial chemoembolization ( TACE ). Methods and results Immunohistochemistry for CAIX , CK 19 and Ep CAM (Ber EP 4) was performed in 57 HCC s, including 40 residual/recurrent tumours adjacent to the TACE treatment site and 17 untreated tumours from the same 40 patients. CAIX was exxpressed in 19 of 40 residual/recurrent HCC s and in two of 17 untreated HCC s. The rate of CAIX immunoreactivity in the treated tumours was significantly higher than that in the non‐treated tumours (47.5% versus 11.8%, P = 0.015). CK 19 and Ep CAM were expressed in six of 19 and in seven of 19 CAIX ‐positive TACE ‐treated HCC s, respectively, but were not expressed in CAIX ‐negative tumours or untreated tumours. There were significant associations between CK 19 and CAIX immunoreactivity, and between Ep CAM and CAIX immunoreactivity ( P = 0.007 and P = 0.003, respectively). Double staining of CAIX and CK 19 showed co‐localization of both proteins in five of six cases. Three of seven Ep CAM ‐positive tumours were also positive for CK 19. Conclusions Hypoxia may trigger the expression of proteins that are normally associated with cholangiocytic/progenitor cell differentiation, suggesting that TACE paradoxically causes an aggressive tumour phenotype.