Cancer Biomarkers - Volume 5, issue 3

Authors: Li, Jin-Hua | Man, Yan-Gao

Article Type: Research Article

Abstract: Our previous studies revealed that Wilms' tumor 1 (WT-1) protein was highly expressed in breast myoepithelial (ME) and endothelial cells. As the human breast tissue is rich in ME cells and blood vessels, our current study intended to assess whether WT-1 immunohistochemistry may have dual usages in evaluation of the ME cells and micro-vessel density. Consecutive sections were prepared from breast tumors with co-existing normal, hyperplastic, and neoplastic components. Consecutive sections were immunostained for WT-1 and a panel of ME and endothelial cell markers. From each case, 4–5 randomly selected duct clusters were photographed, and the percentages of positive cells …for these molecules were compared. Similar to ME cell marker CD10 and smooth muscle actin (SMA), WT-1 expression was preferentially seen in ME cells, and over 90% of WT-1 positive ME cells were immunoreactive to CD10 and SMA. Distinct WT-1 expression was also seen in endothelial cells, and over 90% of WT-1 positive endothelial cells were positive for blood vessel specific markers. With tumor progression, the percentage and intensity of WT-1 positivity decreased in ME cells, whereas increased in endothelial cells. These finding suggest that WT-1 immunohistochemistry may be used to assess both the ME cells and micro-vessel density. Show more

Keywords: Cancer biomarkers, WT-1 protein, myoepithelial cells, vascular density, tumor invasion

DOI: 10.3233/CBM-2009-0595

Citation: Cancer Biomarkers, vol. 5, no. 3, pp. 109-116, 2009

Authors: Olofsson, M. Hägg | Cummings, J. | Fayad, W. | Brnjic, S. | Herrmann, R. | Berndtsson, M. | Hodgkinson, C. | Dean, E. | Odedra, R. | Wilkinson, R.W. | Mundt, K.E. | Busk, M. | Dive, C. | Linder, S.

Article Type: Research Article

Abstract: Pharmacodynamic (PD) assays should be used before advancing new drugs to clinical trials. Most PD assays measure the response to drugs in tissue, a procedure which requires tissue biopsies. The M30-Apoptosense® ELISA is a PD biomarker assay for the quantitative determination of caspase-cleaved cytokeratin 18 (CK18) released from apoptotic carcinoma cells into blood. We here demonstrate that whereas the M30-Apoptosense® ELISA assay detects human caspase-cleaved CK18, the mouse and rat CK18 caspase cleavage products are detected with low affinity. The M30-Apoptosense® ELISA therefore facilitates the determination of drug-induced apoptosis in human tumour xenografts in rodents using plasma samples, largely independently …from host toxicity. Increases of caspase-cleaved CK18 were observed in plasma from different carcinoma xenograft models in response to anticancer drugs. The appearance caspase-cleaved CK18 in plasma was found to reflect formation of the caspase-cleaved epitope in FaDu head-neck carcinomas and in cultured cells. The M30-Apoptosense® assay allows determination of tumour response in blood from xenograft models and from patients, providing a powerful tool for translational studies of anticancer drugs. Show more

Keywords: Cancer therapy, biomarkers, apoptosis

DOI: 10.3233/CBM-2009-0597

Citation: Cancer Biomarkers, vol. 5, no. 3, pp. 117-125, 2009

Authors: Shukla, Sanjeev | Pranay, Atul | D'Cruz, Anil K. | Chaturvedi, Pankaj | Kane, Shubhada V. | Zingde, Surekha M.

Article Type: Research Article

Abstract: Autoantibody response to tumor antigens has been widely used to identify novel tumor markers for different cancers, including that of the head and neck. The oral cavity, which is in the head and neck region, comprises of many sub sites with distinct biologies and incidence of cancer of each sub site of the oral cavity is different. It is anticipated therefore that each sub site of the oral cavity may elicit a differential autoantibody response. This report evaluates the autoantibody response in 15 patients with cancer of gingivo-buccal complex and in 15 patients with cancer of tongue using Immunoproteomics, and …shows that the autoantibody response to alpha-enolase, HSP 70, peroxiredoxin-VI, annexin II, pyruvate kinase, alpha-tubulin, beta-tubulin, ATP synthase, triose phosphate isomerase and aldose reductase seen in patients with cancer of gingivo-buccal complex is absent in patients with cancer of tongue. This suggests that cancer of these sub sites should be studied separately because of their different biology and emerging site specific molecular signatures including autoantibody responses to ensure unambiguous clinical interpretations. Show more

Keywords: Autoantibodies, tongue, gingivo-buccal complex, tumor antigen, immunoproteomics

DOI: 10.3233/CBM-2009-0604

Citation: Cancer Biomarkers, vol. 5, no. 3, pp. 127-135, 2009

Authors: Lee, Gregory

Article Type: Research Article

Abstract: Background: RP215 was the first generated monoclonal antibody which recognizes specifically carbohydrate-associated epitope(s) localized in the variable region of the cancer cell-expressed immunoglobulin heavy chains, designated in general as CA215. Clinical evaluations were performed to assess if RP215 can be utilized in immunoassays to determine serum levels of CA215 among ovarian or cervical cancer patients for monitoring purposes. Methods: By using immunoassays, serum CA215 levels were determined from cervical or ovarian cancer patients and evaluated based on their respective clinical stages as well as the conditions of clinical treatments. Results: Multi-center clinical trials were performed with …frozen serum specimens of patients with ovarian or clinical cancers to determine the efficacy of RP215-based immunoassays. In the case of ovarian cancer, CA215 immunoassay kit has a sensitivity of 46–68% as compared to 46–70% for that of the corresponding CA125 kit. When both markers were combined for simultaneous monitoring of cancer patients, the sensitivity could be as high as 72–87%. Further analysis revealed that serum CA215 levels among cancer patients are well correlated with stages of tumor progression as well as surgical or radio/chemo treatments. Conclusions: The results of these multi-center clinical studies suggest that CA215 is a suitable pan cancer marker for the monitoring of ovarian/cervical cancers and maybe of several others which express CA215 and can be detected in human circulations. Show more

Keywords: CA215, pan cancer marker, cancer cell-expressed immunoglobulins, carbohydrate-associated epitope, RP215 monoclonal antibody, monitoring of human cancers, in vitro diagnostics

DOI: 10.3233/CBM-2009-0610

Citation: Cancer Biomarkers, vol. 5, no. 3, pp. 137-142, 2009

Authors: Kissel, Heather D. | Galipeau, Patricia C. | Li, Xiaohong | Reid, Brian J.

Article Type: Research Article

Abstract: Loss of heterozygosity (LOH) has been shown to be a promising biomarker of cancer risk in patients with premalignant conditions. In this study we describe analytical validation in clinical biopsy samples of a SNP-based pyrosequencing panel targeting regions of LOH on chromosomes 17p and 9p including TP53 and CDKN2A tumor suppressor genes. Assays were tested for analytic specificity, sensitivity, efficiency, and reproducibility. Accuracy was evaluated by comparing SNP-based LOH results to those obtained by previously well-studied short tandem repeat polymorphisms (STRs) in DNA derived from different tissue sources including fresh-frozen endoscopic biopsies, samples from surgical resections, and formalin-fixed paraffin-embedded sections. …A 17p/9p LOH panel comprised of 43 SNPs was designed to amplify with universal assay conditions in a two-step PCR and sequence-by-synthesis reaction that can be completed in two hours and 10 minutes. The methods presented can be a model for developing a SNP-based LOH approach targeted to any chromosomal region of interest for other premalignant conditions and this panel could be incorporated as part of a biomarker for cancer risk prediction, early detection, or as entry criteria for randomized trials. Show more

Keywords: Pyrosequencing, CDKN2A, TP53, LOH, biomarkers, translational research, Barrett's esophagus, esophageal cancer, esophageal adenocarcinoma, cancer risk prediction

DOI: 10.3233/CBM-2009-0618

Citation: Cancer Biomarkers, vol. 5, no. 3, pp. 143-158, 2009