LAUSR

To evaluate cytokeratin 19 expression in normal and cancerous tissues, 15,977 samples from 122 tumor types and 608 samples of 76 normal tissue types were analyzed by immunohistochemistry. In normal tissues, CK19 expression occurred in epithelial cells of most glandular organs but was strictly limited to the basal cell layer of non-keratinizing squamous epithelium and absent in the skin. CK19 expression in ≥90% of cases was seen in 34% of the tumor entities including the adenocarcinomas of the pancreas (99.4%), colorectum (99.8%), esophagus (98.7%), and stomach (97.7%) as well as breast cancer (90.0%-100%), high grade serous (99.1%) or endometroid (97.8%) ovarian cancer, and urothelial carcinoma (92.6%-100%). A low CK19 positivity rate (0.1-10%) was seen in 5 of 122 tumor entities including hepatocellular carcinoma and seminoma. A comparison of tumor versus normal tissue findings demonstrated that up-regulation and down-regulation of CK19 can occur in cancer and that both alterations can be linked to unfavorable phenotype. CK19 down regulation was linked to high grade (p=0.0017) and loss of ER- and PR-expression (p<0.0001 each) in invasive breast carcinoma of no special type. CK19 up regulation was linked to nodal metastases in neuroendocrine tumors and papillary thyroid carcinomas (p<0.05 each) and to poor grade in clear cell renal cell carcinoma (p<0.05). CK19 up regulation was particularly common in squamous cell carcinomas. We concluded that CK19 immunohistochemistry might separate primary liver cell carcinoma from liver metastases, seminoma from other testicular tumors, and helps in the detection of early neoplastic transformation in squamous epithelium.