Cancer stem cells in hepatocellular carcinoma - an immunohistochemical study with histopathological association

Abstract

Background & objectives:Cancer stem cells (CSCs) may be responsible for tumour recurrence and resistance to chemotherapy in hepatocellular carcinoma (HCC). This study was carried out to evaluate the association between histological parameters and liver CSCs (LCSC) in HCC, and to compare distribution of liver CSCs in HCC associated with and without hepatitis B virus (HBV) infection.Methods:Seventy nine tumours (49 surgical resections from 46 patients, and 30 from autopsy) were reviewed. Immunohistochemical staining for the LCSC marker EpCAM (epithelial cell adhesion molecule), liver progenitor cell (LPC) markers CK19 (cytokeratin 19) and neural cell adhesion molecule (NCAM) were performed and were associated with histological features of tumour behaviour.Results:Thirty three tumours (41.8%) showed positive staining for EpCAM. CK19 and NCAM expression were seen in 26 (32.9%) and four (5.1%) tumours, respectively. The expression of EpCAM and CK19 was significantly associated with each other (P<0.001). EpCAM expression was significantly associated with clinical and histological features indicating aggressive tumour behaviour, including younger age of onset, higher serum alpha foetoprotein (AFP) levels, tumour cell dedifferentiation, increased mitotic activity, and vascular invasiveness. There was no significant difference in expression of EpCAM, CK19 and NCAM between HBV positive and negative HCC.Interpretation & conclusions:The LCSC marker EpCAM was expressed in less than half of HCC, was independent of HBV aetiology, and was strongly associated with clinical and histological features of aggressive tumour behaviour. Positive staining for CK19 suggests a possible LPC origin of the EpCAM positive HCCs.

Cancer stem cells in hepatocellular carcinomas

“…The strategy would entail identification of CSCs through markers and their subsequent targeting by appropriate molecules. While the authors of the present study suggest that the expression of EpCAM in CSCs is possibly higher in Indian population than in the West 18 , high expression of EpCAM has also been reported from elsewhere 20 21 . Obviously the identification of these markers would depend on several factors including the sensitivity of the detection method and the expression of these markers in stem cells.…”

“…CK19 expression was associated with poor tumour differentiation, MVI and PVT. The authors hence concluded that EpCAM could be used in future as a therapeutic target in HCC 18 .…”

“…Matthai and Ramakrishnan 18 in this issue studied the immunohistochemical (IHC) expression of CSC markers, such as EpCAM, CK19 and neural cell adhesion molecule (NCAM, CD56) in 79 surgical specimens of hepatocellular carcinoma and associated their expression patterns with histological parameters, aetiological factors, clinical tumour behaviour and serum tumour markers, such as alfa-foetoprotein (AFP) levels. Around 41.8 per cent cases of HCC were positive for EpCAM and 32.9 per cent cases were positive for CK19.…”

Identification of Aging-Related Genes Associated With Clinical and Prognostic Features of Hepatocellular Carcinoma

“…CDK1 was reportedly amplified in HCC tissues and is significantly associated with poor OS (Wu et al, 2018 ). CDK1 expression is positively correlated with tumor stemness indices, and growing evidence suggests that the key biological processes of tumors, such as invasion, metastasis, and therapeutic resistance to chemotherapy and radiotherapy, are largely dependent on tumor stem cells (Matthai and Ramakrishna, 2015 ). In the current study, a significant increase in RNAss was observed in the high-risk group compared with the low-risk group, which also demonstrated the adverse effect of high RNAss on the prognosis of HCC patients.…”

EpCAM- and/or NCAM-Expressing Hepatocellular Carcinoma in Which Behavior of Hepatic Progenitor Cell Marker-Positive Cells Are Followed

“…Furthermore, we found that EpCAM expression, des-γ-carboxy prothrombin ≥300 mAU/mL, age ≥60 years, and Child-Pugh class B or C were independent prognostic factors of poor outcome and were used in a new scoring system for HCC prognosis after operation [12, 13]. Matthai and Ramakrishna [14] reported the frequency of EpCAM-expressing HCC. Thirty-three (41.8%) of the 79 HCCs, comprising 16 (32.7%) tumors in the surgical group and 17 (56.7%) in the autopsy group, showed positive staining for EpCAM.…”