Quantitative evaluation of vimentin expression in tumour stroma of colorectal cancer

Recent studies have identified vimentin, a type III intermediate filament, among genes differentially expressed in tumours with more invasive features, suggesting an association between vimentin and tumour progression. The aim of this study, was to investigate whether vimentin expression in colon cancer tissue is of clinical relevance. We performed immunostaining in 142 colorectal cancer (CRC) samples and quantified the amount of vimentin expression using computer-assisted image analysis. Vimentin expression in the tumour stroma of CRC was associated with shorter survival. Overall survival in the high vimentin expression group was 71.2% compared with 90.4% in the low-expression group (P=0.002), whereas disease-free survival for the high-expression group was 62.7% compared with 86.7% for the low-expression group (P=0.001). Furthermore, the prognostic power of vimentin for disease recurrence was maintained in both stage II and III CRC. Multivariate analysis suggested that vimentin was a better prognostic indicator for disease recurrence (risk ratio=3.5) than the widely used lymph node status (risk ratio=2.2). Vimentin expression in the tumour stroma may reflect a higher malignant potential of the tumour and may be a useful predictive marker for disease recurrence in CRC patients

The human keratins: biology and pathology

The keratins are the typical intermediate filament proteins of epithelia, showing an outstanding degree of molecular diversity. Heteropolymeric filaments are formed by pairing of type I and type II molecules. In humans 54 functional keratin genes exist. They are expressed in highly specific patterns related to the epithelial type and stage of cellular differentiation. About half of all keratins—including numerous keratins characterized only recently—are restricted to the various compartments of hair follicles. As part of the epithelial cytoskeleton, keratins are important for the mechanical stability and integrity of epithelial cells and tissues. Moreover, some keratins also have regulatory functions and are involved in intracellular signaling pathways, e.g. protection from stress, wound healing, and apoptosis. Applying the new consensus nomenclature, this article summarizes, for all human keratins, their cell type and tissue distribution and their functional significance in relation to transgenic mouse models and human hereditary keratin diseases. Furthermore, since keratins also exhibit characteristic expression patterns in human tumors, several of them (notably K5, K7, K8/K18, K19, and K20) have great importance in immunohistochemical tumor diagnosis of carcinomas, in particular of unclear metastases and in precise classification and subtyping. Future research might open further fields of clinical application for this remarkable protein family

Keratin polypeptides in malignant epithelial liver tumors. Differential diagnostic and histogenetic aspects.

Five monoclonal antibodies recognizing different keratin polypeptides in immunoblotting or different epithelial cell types in complex tissues were studied for their suitability as reagents for the differential diagnosis of primary and secondary malignant epithelial liver tumors. The broad specificity keratin antibodies lu-5 and KL-1 stained all epithelial liver neoplasms. In contrast the antibodies CK-7 (Ker-7-specific), CK-2 (Ker-18-specific) and KA-4 (Ker-19-specific in liver) allow these neoplasms to be divided into three groups: Hepatocellular carcinomas were CK-2-positive and CK-7-negative. Cholangiocellular carcinomas, liver metastases of extrahepatic bile duct carcinomas, liver metastases of a ductal carcinoma of breast, and a follicular thyroid carcinoma were stained positively by CK-2, CK-7, and KA-4. In 1 of 6 hepatocellular carcinomas neoplastic hepatocytes were focally labeled by KA-4. In a focal nodular hyperplasia of the liver modified hepatocytes were decorated not only by CK-2 but also by CK-7 and KA-4. Liver metastases of colorectal adenocarcinomas and of a carcinoid tumor were stained positively by CK-2 and KA-4 but not by CK-7