Positive expression of Midkine predicts early recurrence and poor prognosis of initially resectable combined hepatocellular cholangiocarcinoma

Abstract

BackgroundPost-surgical prognosis is usually poor for combined hepatocellular cholangiocarcinoma (CHCC-CC), a rare primary liver cancer. Although midkine (MK) is a prognostic biomarker for several known cancers, it is not known whether it can be used as such in resectable CHCC-CC. This study examined whether MK expression can predict recurrence and survival in patients with resectable CHCC-CC.MethodsWe retrospectively enrolled 52 patients with resectable CHCC-CC who had received curative hepatic resections. MK expression was assessed in post-surgical immunohistochemical studies of specimens in paraffin blocks. Clinical outcomes were analyzed from medical records.ResultsTwo-year disease-free and three-year overall survival rates were 42.1% and 44.6%. MK was expressed in 30 patients. Univariate analysis showed patients positively expressing MK had a significantly poorer 2-year disease free and three-year overall survival. Multivariate analysis found positive MK expression independently predicted recurrence.ConclusionsPositive expression of MK predicts poor prognosis in patients with resectable CHCC-CC.

Competing risk analyses of overall survival and cancer-specific survival in patients with combined hepatocellular cholangiocarcinoma after surgery

“…In addition, there was no a TNM stage system which is specially designed for CHCC. It was reported that the differences of clinical features among CHCC, HCC and ICC could lead to the variations of prognostic factors [12, 13]. There were also many factors, such as age, gender and tumor grade, which were shown to have great impact on survival.…”

Update on the Genetics of and Systemic Therapy Options for Combined Hepatocellular Cholangiocarcinoma

“…Even following treatment for localized disease it is common for the disease to recur, often with unresectable regional or distant/metastatic disease; ( 4 , 40 , 76 , 78 ) tumor recurrence rates at 1, 3, and 5 years were 60.8, 71.8, and 80.7%, respectively in one study, and median disease-free survival of 10 months has been reported ( 4 , 5 , 69 , 78 ). Recurrence rates seem to be non-significantly different in comparison to HCC and ICC, but mOS after recurrence tends to be worse than HCC and possibly worse than ICC ( 4 , 5 , 78 ).…”

“…In patients with localized cHCC-ICC and good performance status, surgical resection may provide the chance of long-term benefit, for example, 5 year survival rate of 30% has been reported ( 12 , 68 , 69 ). These tumors show locoregional spread in similar patterns to HCC (hepatic and portal venous invasion) and to ICC (lymph node dissemination).…”

Development and Validation of Nomogram to Predict Very Early Recurrence of Combined Hepatocellular-Cholangiocarcinoma After Hepatic Resection: A Multi-Institutional Study

“…Previous studies reported early recurrence (ER) (ie, recurrence within 2 years after surgery) rate of 57-75% and 6-months recurrence rate of about 40% or so. 6,7,[9][10][11] Therefore, the research on VER of cHCC is of vital importance.…”