Malignancy of Keratin 19 positive hepatocellular carcinomas in dogs and cats.

Abstract

A study by van Sprundel et al. has shown that 12% of canine hepatocellular carcinomas (HCCs) expressed Keratin 19 (K19). These K19 positive tumors are more invasive and metastasize faster compared to K19 negative tumors. In this study we looked at the malignancy of K19 positive HCCs compared to K19 negative HCCs by staging and grading and looking at the difference in expression of metastasis markers. Immunohistochemistry was performed for K19 on 145 liver tumor samples. Of these samples a selection of six K19 negative and five K19 positive tumors were stained for metastasis markers: BMI-1, EZH2, NF2, NF2-P, Laminin1, CD29, Glypican3, PDGFRα, MTSS1, S100A6 and MAC387. Results: In our study, 20% of all hepatocellular carcinomas expressed Keratin 19. These positive tumors are poorly differentiated, show pleiomorfism, multinucleated cells, and mitosis and often metastasize. While K19 negative tumors still resemble healthy liver, are well encapsulated and do not metastasize. Metastasis markers BMI-1, Laminin1, PDGRFα, S100A6 and MAC387 are higher expressed in K19 positive HCCs compared to K19 negative HCCs. There was a lower expression in K19 positive HCCs, compared to K19 negative HCCs, of NF2 and NF2-P. Conclusion: Keratin 19 positive hepatocellular carcinomas are more malignant compared to keratin 19 negative carcinomas and keratin 19 positive hepatocellular carcinomas express many metastasis markers.