Aim: To investigate whether expressing biliary phenotype predicted poor outcome after the surgical treatment in primary liver cancers.
Methods: Out of 204 patients that underwent liver resection due to hepatocellular carcinoma (HCC), liver specimens of 70 patients with HCC were evaluated for biliary components by cytokeratin (CK) 19 immunostain (CK19⁻ HCC and CK19⁺ HCC). CK19 positivity was defined as membranous and/or cytoplasmic expression in ≥ 5% of tumor cells with moderate or strong intensity. Patients with other primary liver cancers, such as combined HCC and cholangiocarcinoma (cHCC-CC), intrahepatic cholangiocarcinoma (ICC) who received curative liver resection, were also included in the study. Clinical characteristics of CK19⁻ HCC and CK19⁺ HCC patients, including survival outcome after curative liver resection, were compared with that of cHCC-CC and ICC patients.
Results: The overall survival (OS) rate of CK19⁻ HCC (n = 49) after the curative surgical treatment was 90.7%, and 80.4% at 1 and 5 years after the resection. OS rate of CK19⁺ HCC (n = 21) was 74.3%, 28.9% and OS rate of cHCC-CC (n = 22) was 66.7%, 32.2% at 1 and 5 years after the surgery. For ICC (n = 19), 1 and 5-year-OS rate was 50.2% and 14.3% after the curative resection. The OS rates of CK19⁺ HCC and cHCC-CC were significantly lower than that of CK19⁻ HCC, but higher than the OS rate of ICC (P = 0.000). There was no statistically significant difference in OS rate between CK19⁺ HCC and cHCC-CC. The disease free survival (DFS) rate of CK19⁻ HCC was 72.0% and 54.5% at 1 and 3 years after the surgical treatment. DFS rate of CK19⁺ HCC was 53.3%, 34.3% and DFS rate of cHCC-CC was 51.5%, 39.2% at 1 and 3 years after the resection. For ICC, 1 and 3-year-DFS rate was 28.0% and 14.0% after the curative resection. DFS rate of CK19⁻ HCC was significantly higher than that of ICC (P = 0.017), but marginally higher than DFS rate of either CK19⁺ HCC or cHCC-CC (P = 0.097, P = 0.089, respectively). Predictors of outcome after the surgery of primary liver cancer were pathology of the resected mass, existence of microvascular invasion and accompanying satellite nodule.
Conclusion: Primary liver cancers with biliary components tended to show poorer surgical outcome. This suggested that immuno-phenotype of liver cancers was as important as their morphological classification.
Keywords: Cytokeratin 19; Hepatectomy; Hepatocellular carcinoma; Intrahepatic cholangiocarcinoma; Liver cancers.