Preoperative Locoregional Therapy May Relate with Stemness and Distinct Transitions Between Epithelial and...

Locoregional therapy (LRT) might impel hepatocellular carcinoma (HCC) to exhibit different phenotypes by modulating tumoral cell adaptation. HCCs presurgically treated with LRT were studied, focusing on stemness and mesenchymal features.

Clinicopathological and immunohistochemical data (Ki67, p53, EpCAM, CK19, CK7, ASMA and vimentin expression) were considered in 89 HCC nodules (30 treated with LRT; 59 non-treated), comprising 46 liver transplanted/surgically resected patients.

In LRT group, well and poorly differentiated tumors without fibrous encapsulation were predominant (P < 0.05) and peritumoral necroinflammation severity tended to be greater. Peritumoral Ki67 expression was higher (P < 0.05) and p53, EpCAM, CK19 and CK7 peritumoral expression was relevant after LRT, where ablated carcinomas displayed higher peritumoral CK19 expression (P < 0.05). Tumoral ASMA and vimentin expression was higher in non-LRT group (P < 0.05). In LRT group, an exclusive association between progenitor/cholangiocytic cell and mesenchymal markers expressed by tumoral cells was observed (P < 0.05): EpCAM tumoral expression associated with vimentin stromal expression; tumoral CK19 expression associated with stromal ASMA expression; tumoral CK7 expression associated with tumoral vimentin expression.

Peritumoral cellular proliferation and expression of progenitor/cholangiocytic cell markers seem to be more frequent after LRT, with a distinctive epithelial-mesenchymal interplay and plasticity in peritumoral and tumoral compartments.