Keratin 20 - A diagnostic and prognostic marker in colorectal cancer?
Lars Harbaum1, Marion J. Pollheimer1, Peter Kornprat2, Richard A. Lindtner1, Andrea Schlemmer3, Peter Rehak4 and Cord Langner1
1Institute of Pathology, 2Department of Surgery, Division of General Surgery, 3Institute for Medical Informatics, Statistics and Documentation and 4Department of Surgery, Research Unit for Biomedical Engineering & Computing, Medical University of Graz, Graz, Austria.
Offprint requests to: Cord Langner, MD, Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, A-8036 Graz, Austria. e-mail: cord.langner@medunigraz.at
Summary. Colorectal cancer cells characteristically show strong expression of keratin 20 (K20) and lack expression of keratin 7 (K7). The biological significance of reduced K20 expression, however, is unclear. 381 colorectal cancers with 148 corresponding metastases were evaluated for K20 and K7 expression by immunohistochemistry using a tissue microarray technique. K20 immunoreactivity was assessed semiquantitatively as either negative, low (<50% of cancer cells) or high (≥50% of cancer cells). Progression-free and cancer-specific survivals were determined using the Kaplan-Meier method. Expression of K20 was observed in 348 out of 372 (94%) evaluable primary tumors, with 135 (36%) cases showing low K20 and 213 (57%) cases high K20 expression, while 24 (6%) tumors completely lacked K20 immunoreactivity. Reduced K20 expression (lack of staining or low expression) was significantly associated with poor differentiation, large tumor size and mismatch repair deficiency, but did not significantly affect patients’ outcome. Immunoreactivity of K20 and K7 in metastatic tissues matched well with that of corresponding primary tumors, with high concordance for lymph node (p<0.001) and distant metastases (p<0.001), respectively. In conclusion, our data illustrate the value of keratin subtyping in carcinoma of unknown primary (CUP) syndrome: K20 expression is common in colorectal cancer and the K20 high / K7 negative immunoprofile represents the predominant phenotype. Reduced K20 expression may, however, lead to false-negative assessment of metastatic deposits if only small amounts of tissue are obtained (e.g. in needle biopsies), particularly in poorly differentiated cancers. Reduced expression of K20 may be used to select tumors for microsatellite instability testing. Histol Histopathol 27, 347-356 (2012)
Key words: Colorectal carcinoma, Keratin 20, Keratin 7, Carcinoma of unknown primary, Prognosis
DOI: 10.14670/HH-27.347