Introduction We evaluated whether CK19, one of the main cytoskeleton proteins of epithelial cells, is released as full-length protein from viable tumor cells and whether this property is relevant for metastatic progression in breast cancer patients. Methods EPISPOT (EPithelial ImmunoSPOT) assays were performed to analyze the release of full-length CK19 by carcinoma cells of various origins, and the sequence of CK19 was analyzed with mass spectrometry. Additional functional experiments with cycloheximide, Brefeldin A, or vincristine were done to analyze the biology of the CK19-release. CK19EPISPOT was used to detect disseminated tumor cells in bone marrow (BM) of 45 breast cancer patients who were then followed up over a median of 6 years.

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Full-length cytokeratin-19 is released by human tumor cells: a potential role in metastatic progression of breast cancer

Pre-treatment serum squamous cell carcinoma antigen [SCC] levels are elevated in 28-88% of patients with squamous cell cervical cancer, and are related to tumour stage, tumour size, depth of stromal invasion, lymph-vascular space status, parametrial involvement and lymph node status. The clinical relevance of pre-treatment serum SCC assay is still debated. Some authors reported that it has no prognostic value, some others found that it is related to survival at univariate analysis, and some others detected that is an independent prognostic variable for survival. Serial SCC measurements reflect both the tumour response to treatment and the clinical outcome of patients. Increasing SCC levels can precede the clinical diagnosis of recurrent disease in 46-92% of the cases, with a mean lead time ranging from 2 to 8 months. According to some authors serum SCC assay during the follow-up does not improve the cure rate of patients who will ultimately develop a recurrence. However, it has been recently reported that the performance of a positron emission tomography [PET] in patients with asymptomatic SCC elevation can sometimes allow an earlier diagnosis of relapse with a survival benefit. SCC is a more sensitive serum tumour marker than CYFRA 21-1 for squamous cell cervical cancer in most series. Pre-treatment CA 125 levels are raised in 20-75% of patients with cervical adenocarcinoma, and reflect tumour stage, tumour size, histological grade, cervical stromal invasion, lymph-vascular space status and lymph node status. Elevated serum CA 125 has been also detected in patients with squamous cell cervical cancer, but with a positivity rate lower than that found in patients with cervical adenocarcinoma. Pre-treatment CA 125 levels appear to have a prognostic value, and rising serum CA 125 during follow-up may precede or be coincident with the clinical diagnosis of recurrent cervical adenocarcinoma. Serum levels of vascular endothelial growth factor [VEGF] are often elevated in patients with cervical cancer, and decrease significantly after successful treatment. However, the clinical relevance of serum VEGF assay is still investigational.

The serum assay of tumour markers in the prognostic evaluation, treatment monitoring and follow-up of patients with cervical cancer: a review of the literature.

Plasminogen binding to cell surfaces may be important for tumor invasion and other processes that involve cellular migration. In this investigation, the principal plasminogen-binding protein was identified in the plasma membrane fraction of rat hepatocytes. The protein had an apparent mass of 59 kDa, was insoluble in a spectrum of detergents, and was identical to cytokeratin 8 (CK 8) as determined by sequence analysis of nine amino acids at the N terminus of two cyanogen bromide fragments. The 59 kDa protein bound CK 8-specific antibody in western blot analyses. These studies demonstrate that CK 8 or a CK 8-like protein binds plasminogen. Given this newly determined and potentially important CK 8 function, immunofluorescence and immunoelectron microscopy studies were performed to determine whether CK 8 may be present on the external surfaces of unpermeabilized, viable hepatocytes. All of the cells in each preparation were immunopositive with two separate CK 8-specific antibodies. A punctate pattern of immunofluorescence was detected on the cell surface with approximately even intensity from cell to cell. By immunoelectron microscopy, CK 8 was preferentially associated with microvilli. In order to determine whether other epithelial cells express cell-surface CK 8, immunofluorescence and immunoelectron microscopy studies were performed with HepG2 hepatocellular carcinoma cells and with BT20 and MCF-7 breast carcinoma cells. The pattern of antigen expression was equivalent with each cell type and comparable to that observed with hepatocytes. These studies support the hypothesis that CK 8 is associated with the external cell surface where it may express important proteinase receptor function.

A cytokeratin 8-like protein with plasminogen-binding activity is present on the external surfaces of hepatocytes, HepG2 cells and breast carcinoma cell lines

The association of biological markers with cancer has been recognized for many decades. Current interest in markers for cancer arose in the mid 1960s, with the discoveries of alpha-fetoprotein and carcinoembryonic antigen. They were called oncofetal proteins, because of their presence in high concentrations during embryonic development, their virtual disappearance in the neonatal period, and their reappearance with cancers of specific cell types. Essentially, any molecular species may be produced in abnormal amounts or under abnormal circumstances by a tumour, and thereby become useful as a tumour marker. Several tumour markers have been studied in lung cancer. Unfortunately, none of these appear to be sufficiently sensitive and specific to be reliable for screening and diagnostic purposes. However, there is a body of evidence which proves that at least some of these substances may be useful in the evaluation of the course and prognosis of the disease. This review presents data concerning the most studied and interesting tumour markers in lung cancer.

https://erj.ersjournals.com/content/erj/7/1/186.full.pdf

Serum tumour markers in lung cancer: history, biology and clinical applications

Cytokeratins have been extensively used as serum tumour markers for monitoring of disease progression in cancer patients. The source of cytokeratins in the circulation as well as the mechanisms of rel

Björklund

Papers

Specificity and basis of the tissue polypeptide antigen.