Diagnostic and prognostic impact of cytokeratin 19 expression analysis in human tumors: a tissue microarray study of 13,172 tumors

Anne Menz MD a, Rifka Bauer cand. med. a, Martina Kluth PhD
Clara Marie von Bargen MD a, Natalia Gorbokon MD
Florian Viehweger MD a, Maximilian Lennartz MD a, Cosima Völkl MD
Christoph Fraune MD a, Ria Uhlig MD a, Claudia Hube-Magg PhD
Noémi De Wispelaere MD b, Sarah Minner MD a, Guido Sauter MD
Simon Kind MD a, Ronald Simon PhD a,*, Eike Burandt MD
Till Clauditz MD a, Patrick Lebok MD a, Frank Jacobsen MD
Stefan Steurer MD a, Waldemar Wilczak MD a, Till Krech MD
Andreas H. Marx MD d, Christian Bernreuther MD

Received 3 May 2021; accepted 27 May 2021
Available online 6 June 2021

Keywords

Cytokeratin 19 (CK19); Tissue microarray; Immunohistochemistry; Non-neoplastic tissue; Neoplastic tissue

Summary

To evaluate cytokeratin 19 (CK19) 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
(IHC). In normal tissues, CK19 expression occurred in epithelial cells of most glandular
organs but was strictly limited to the basal cell layer of nonkeratinizing 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%e100%), high-grade serous (99.1%) or endometrioid
(97.8%) ovarian cancer, and urothelial carcinoma (92.6%e100%). A low CK19 positivity rate (0.1
e10%) was seen in 5 of 122 tumor entities including hepatocellular carcinoma and seminoma. A comparison
of tumor versus normal tissue findings demonstrated that upregulation and downregulation of
CK19 can occur in cancer and that both alterations can be linked to unfavorable phenotypes. CK19
downregulation was linked to high grade (p Z 0.0017) and loss of estrogen receptore and
progesterone receptoreexpression (p < 0.0001 each) in invasive breast carcinoma of no special type.
CK19 upregulation 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 upregulation
was particularly common in squamous cell carcinomas. We concluded that CK19 IHC 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.
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