Expression of keratin 20 and its clinicopathological significance in intrahepatic cholangiocarcinoma

Abstract

Although the expression of keratin 7 (K7) and K20 is considered to be a useful factor in the differential diagnosis of intrahepatic cholangiocarcinoma (ICC) and metastatic colorectal carcinoma (CRC) of the liver, a proportion of typical ICC retains K20 expression. The frequency and biological significance of K20 expression in ICC remains unclear. We analyzed the expression of K7, K19 and K20 in 66 surgically resected liver tumors consisting of 46 ICCs and 20 metastatic CRCs of the liver and 20 corresponding primary CRCs. In the 46 ICCs, K7, K19 and K20 were expressed in 40 (87%), 45 (98%) and 16 (35%) cases, respectively. K7, K19 and K20 were expressed in 1 (5%), 20 (100%) and 16 (80%) of the 20 primary CRCs and 2 (10%), 20 (100%) and 16 (80%) of the 20 metastatic CRCs, respectively. A combined K7/K20 profile was identified as a good predictor for differentiating ICC and metastatic CRC. K20 expression in ICC was significantly associated with male gender (P=0.034), hilar location (P=0.026), intraductal papillary type (P=0.006), intestinal phenotype (P<0.001) and MUC2 expression (P=0.008). Univariate analysis identified that poor patient survival was significantly associated with histological grade (P=0.020), invasion depth (P=0.005), lymph node metastasis (P=0.012), tumor stage (P=0.004) and vessel invasion (P=0.023). The tumor stage (P=0.002) was a poor independent prognostic indicator, while MUC6 expression (P=0.036) was a good independent prognostic indicator. The survival rate in patients with K20-positive ICC was lower compared to that of patients with K20-negative ICC, but was not statistically significant. Furthermore, the combined K7/K20 immunophenotype was identified to be useful for differentiating ICC and metastatic CRC. K20-positive ICC displays specific characteristics with regards to tumor location and histological subtype. Additionally, MUC6 expression in ICC is a good independent prognostic factor, while K20 expression is more often associated with aggressive biological behavior.

Figure 1

Pancreatobiliary type CC (A) H&E staining, (B) immunostaining for K7 and (C) immunostaining for K20. Almost all cancer cells are positive for K7 and K20. K7⁻/K19⁺/K20⁺ intestinal type CC (D) H&E staining, (E) positive immunostaining for K19 and (F) positive immunostaining for K20. Gastric type CC (G) H&E staining, (H) positive immunostaining for K7 and (I) negative immunostaining for K20. CC, cholangiocarcinoma; H&E, hematoxylin and eosin; K, keratin.