Keratins are popular diagnostic markers in cancer because of their typical signature for tumor cell type and differentiation, while maintaining the specific expression pattern associated with the cell type of origin. Commonly used markers in the immunohistochemical analysis of tumors are K5-K8 and K18-K20. Adenocarcinomas (epithelial cancers arising in glandular tissues) build up the largest group of human epithelial malignancies. As they can originate in various organs, the ability of differentiating a carcinoma according to the tissue of origin is crucial. By using epithelial keratins as diagnostic markers, the best treatment depending on the exact type of cancer can be determined. In general, most adenocarcinomas express K8, K18 and K19. K7 and K20 levels vary depending on cancer type. In unclear cases, keratin typing is often key to assess the correct tumor type. Beyond their role as diagnostic markers, keratins are also useful prognostic indicators in epithelial malignancies.
For instance, in colorectal cancer, reduced expression of K8 and K20 has been associated with epithelial to mesenchymal cancer cell transition – an indicator for higher tumor aggressiveness. Apart from being diagnostic and prognostic markers, several studies support an active role of keratins (e.g. K8 and K18) in cancer cell invasion and metastasis, pointing to a functional role of keratins in tumorgenesis. Further research will reveal whether pharmacological keratin modulation can be used as an adjunct to chemotherapy for improving therapeutic outcomes.