Expression of Keratin 19 Is Related to High Recurrence of Hepatocellular Carcinoma after Radiofrequency Ablation

Abstract

Objective: Keratin (K) 19 positivity has been reported to be a useful predictive marker for recurrence in patients with hepatocellular carcinoma (HCC) who have undergone hepatic resection. We investigated the clinical usefulness of K19 positivity in patients who had received curative radiofrequency ablation (RFA). Methods: We retrospectively evaluated the clinicopathological features, including imaging and K19 expression, in 246 patients with HCC who were within the Milan criteria and had received curative RFA. Using a two-step insertion method, tumor biopsies were obtained just prior to RFA and were evaluated histologically. Results: Tumor seeding due to liver biopsy and RFA was not observed. Ten patients (4.1%) had K19-positive HCC. Imaging findings were similar between K19-positive and -negative HCC (p = 0.187). Nine out of 10 patients (90%) who had K19-positive HCC had recurrence of HCC after RFA, and intrahepatic recurrences were observed within 12 months in 6 out of 10 (60.0%). K19 positivity was a significant risk factor for recurrence (p < 0.0001) and early recurrence (<1 year after RFA; p =0.012). K19 expression (p = 0.016) was an independent risk factor for tumor status exceeding the Milan criteria after RFA. Conclusion: Expression of K19 is related to high recurrence of HCC after curative RFA.

1047 Keratin 19: A Key Role Player in the Invasion of Human Hepatocellular Carcinomas

“…Despite the possible overestimation or underestimation of protein expression, we confirmed the prognostic value of K19 expression in diagnostic needle biopsies. 4 In this study, EPCAM did not prove to have the same prognostic value as K19. This could be explained by the fact that in regenerating liver, EPCAM is a much broader marker than K19, as it also marks the progeny of the HPCs, the intermediate hepatocytes, similar to K7.…”

“…[2][3][4][5][6] In 2006, our group was the first to describe the clinicopathological and prognostic relevance of K19 in a Caucasian series of HCCs as it was linked with a high recurrence after transplantation. 7 Subsequently, we started a prospective study on a Caucasian series of 242 consecutive HCC samples with a different range of aetiologies and performed a detailed evaluation of the clinicopathological relevance of K19.…”

Expression of K19 and K7 in dysplastic nodules and hepatocellular carcinoma

“…As K19 and/or K7-positive HCC cells were not diffusely present in this study, the expression frequencies in the 3 mm TMA core may have been underestimated. This hypothesis was supported by a recent study which demonstrated that K19 expression in biopsy specimens for HCC taken prior to radiofrequency ablation is extremely low (4.1%) (8). Assessment of a biomarker in a small TMA tissue core may not accurately reflect the assessment that would be obtained from a whole section analysis due to intratumoral heterogeneity (30).…”

“…K19 expression in HCC is associated with recurrence, metastasis and poor prognosis (5)(6)(7)(8). Recent studies have postulated that K19-positive HCCs originates from hepatic progenitor cells (HPCs) (5,9,10).…”

Reduced Organic Anion Transporter Expression Is a Risk Factor for Hepatocellular Carcinoma in Chronic Hepatitis C Patients: A Propensity Score Matching Study

“…As for curatively treated HCC patients, tumor differentiation or progenitor-cell feature markers of cancerous tissue have been identified as predictors of recurrence [13,14]. In contrast, only several reports have mentioned the importance of background noncancerous liver tissue and the microenvironment; these are predictive of HCC recurrences [15,16].…”