Expression of Molecular Differentiation Markers Does Not Correlate with Histological Differentiation Grade in Intrahepatic Cholangiocarcinoma.
The differentiation status of tumor cells, defined by histomorphological criteria, is a prognostic factor for survival of patients affected with intrahepatic cholangiocarcinoma (ICC). To strengthen the value of morphological differentiation criteria, we wished to correlate histopathological differentiation grade with expression of molecular biliary differentiation markers and of microRNAs previously shown to be dysregulated in ICC. We analysed a series of tumors that were histologically classified as well, moderately or poorly differentiated, and investigated the expression of cytokeratin 7, 19 and 903 (CK7, CK19, CK903), SRY-related HMG box transcription factors 4 and 9 (SOX4, SOX9), osteopontin (OPN), Hepatocyte Nuclear Factor-1 beta (HNF1β), Yes-associated protein (YAP), Epithelial cell adhesion molecule (EPCAM), Mucin 1 (MUC1) and N-cadherin (NCAD) by qRT-PCR and immunostaining, and of miR-31, miR-135b, miR-132, miR-200c, miR-221 and miR-222. Unexpectedly, except for subcellular location of SOX9 and OPN, no correlation was found between the expression levels of these molecular markers and histopathological differentiation grade. Therefore, our data point toward necessary caution when investigating the evolution and prognosis of ICC on the basis of cell differentiation criteria.
de Duve Institute, Université catholique de Louvain, Avenue Hippocrate 75, B-1200 Brussels, Belgium.
Céline
C
Demarez
Division of Hepato-Biliary and Pancreatic Surgery, Department of Abdominal Surgery and Transplantation, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Avenue Hippocrate 10, B-1200 Brussels, Belgium.
Catherine
C
Hubert
Service de Pathologie Clinique, Centre Hospitalier Universitaire Vaudois, Université de Lausanne, CH-1011 Lausanne, Switzerland.
Christine
C
Sempoux
de Duve Institute, Université catholique de Louvain, Avenue Hippocrate 75, B-1200 Brussels, Belgium.
Frédéric P
FP
Lemaigre
D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D018281:Cholangiocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis
D014408:Biomarkers, Tumor