Cancer Biomarkers - Volume 6, issue 1

Authors: Trojani, Alessandra | Montillo, Marco | Nichelatti, Michele | Tedeschi, Alessandra | Colombo, Chiara | Veronese, Silvio | Mura, Maria Angela | Ricci, Francesca | Scarpati, Barbara | Colosimo, Anna | Lodola, Milena | Morra, Enrica

Article Type: Research Article

Abstract: Background: New prognostic factors such as IgVh mutational status, ZAP-70 protein expression and cytogenetic abnormalities have shown to offer important prognostic information for patients with chronic lymphocytic leukemia (CLL). Our aim was to evaluate the optimal cut-off for IgVh mutational status, ZAP-70 expression and cytogenetic abnormalities in association with disease progression defined as the need for treatment within 3 years from diagnosis in 170 patients with B-CLL. Design and methods: Receiver operating characteristics (ROC) analysis and multivariate general linear models (GLMs) were used to investigate the most significant cut-off values of these biomarkers and their prognostic impact. …Results: Our findings estimated that the optimal cut-off for IgVh mutation status and for ZAP-70 protein expression was 97% and 16.5% respectively and a high concordance between the two was demonstrated. We identified 30% as being the best-cut-off for 17p-, 11q- and 6q-. In univariate analysis 17p- was found to be a significant predictor of the event only for the whole population. Multivariate analysis including all biological parameters, identified 11q deletion as the only significant regressor. Conclusions: We assessed that IgVh mutational status, ZAP-70 protein and 6q- are powerful prognostic markers. Analyses of all these factors revealed that 11q deletion was the strongest predictor of disease progression in B-CLL. Show more

Keywords: CLL, biomarkers, ZAP-70, IgVh, cytogenetics

DOI: 10.3233/CBM-2009-0114

Citation: Cancer Biomarkers, vol. 6, no. 1, pp. 1-9, 2010

Authors: Srivastava, Shatakshi | Roy, Raja | Singh, Sudhir | Kumar, Praveen | Dalela, Diwakar | Sankhwar, Satya N. | Goel, Apul | Sonkar, Abhinav A.

Article Type: Research Article

Abstract: Urinary bladder cancer is a major epidemiological problem that continues to grow each year. It opens avenues for investigative research for the identification of new disease markers and diagnostic techniques. In this pilot study, utility of non-invasive 1 H NMR spectroscopy has been evaluated for probing the metabolic perturbations occurring in non-muscle invasive urinary bladder cancer. 1 H NMR spectra of urine of bladder cancer patients and controls (healthy and urinary tract infection/bladder stone) (n=103) were acquired at 400MHz. The non-overlapping resonances of citrate, dimethylamine, phenylalanine, taurine and hippurate were first identified and then quantitated by 1 H NMR spectra, …with respect to an external reference sodium-3-trimethylsilylpropionate (TSP). The concentrations of these metabolites were then statistically analyzed. The cancer patients showed significant (p< 0.05) variations in concentration of hippurate and citrate as compared with healthy controls and benign controls. The significant elevation in concentration of taurine was observed in urine of bladder cancer patients, which was below the sensitivity limit of 400MHz in control cases. However, stages Ta, T1 and carcinoma in situ (CIS) cannot be differentiated on the basis of altered metabolite indices but their composition may reflect the biochemical alterations in metabolism of cancer cells. Show more

DOI: 10.3233/CBM-2009-0115

Citation: Cancer Biomarkers, vol. 6, no. 1, pp. 11-20, 2010

Authors: Messiou, C. | deSouza, N.M.

Article Type: Research Article

Abstract: Diffusion Weighted Magnetic Resonance Imaging (DW-MRI) combined with conventional MRI can provide a whole body assessment of metastatic bone disease, improved lesion detection compared to other imaging techniques and a direct quantitative assessment of treatment response. In bone marrow, the presence of fat and bone trabeculae and their changing contributions with disease progression and response to treatment present unique challenges for data acquisition and image interpretation. This article discusses these challenges and reviews the potential of DW-MRI to provide a biomarker of response in metastatic bone disease.

Keywords: Tumour therapy, cancer, diffusion, bone, magnetic resonance imaging

DOI: 10.3233/CBM-2009-0116

Citation: Cancer Biomarkers, vol. 6, no. 1, pp. 21-32, 2010

Authors: Ali-Fehmi, Rouba | Chatterjee, Madhumita | Ionan, Alexei | Levin, Nancy K. | Arabi, Haitham | Bandyopadhyay, Sudeshna | Shah, Jay P. | Bryant, Christopher S. | Hewitt, Stephen M. | O'Rand, Michael G. | Alekseev, Oleg M. | Morris, Robert | Munkarah, Adnan | Abrams, Judith | Tainsky, Michael A.

Article Type: Research Article

Abstract: Biomarkers for early detection of cancer have great clinical diagnostic potential. Numerous reports have documented the generation of humoral immune responses that are triggered in response to changes in protein expression patterns in tumor tissues and these biomarkers are referred to as tumor associated antigens (TAAs). Using a high-throughput technology, we previously identified 65 proteins as diagnostically useful TAAs by profiling the humoral immune responses in ovarian cancer (OVCA) patients. Here we determined the expression status of some of those TAAs in tissues from OVCA patients. The protein expression patterns of 4 of those 65 antigens, namely NASP, RCAS1, Nijmegen …breakage syndrome1 (NBS1) and eIF5A, along with p53 and Her2 (known molecular prognosticators) and two proteins that interact with NBS1, MRE11 and RAD50, were assessed by immunohistochemistry (IHC). NASP and RCAS1 proteins were more frequently expressed in ovarian cancer tissues than with normal ovarian tissue and serous cystadenomas and MRE11 was less frequently expressed. When evaluated simultaneously, only NASP and MRE11 remained statistically significant with sensitivity of 66% and specificity of 89%. None of these proteins' expression levels were prognostic for survival. Together, our results indicate that occurrence of humoral immune responses against some of these TAAs in OVCA patients is triggered by antigen protein overexpression. Show more

Keywords: Ovarian cancer, phage display, tissue biomarker, humoral immune response, tissue microarray

DOI: 10.3233/CBM-2009-0117

Citation: Cancer Biomarkers, vol. 6, no. 1, pp. 33-48, 2010

Authors: Agostini, Marco | Enzo, Maria Vittoria | Morandi, Luca | Bedin, Chiara | Pizzini, Silvia | Mason, Silvia | Bertorelle, Roberta | Urso, Emanuele | Mescoli, Claudia | Lise, Mario | Pucciarelli, Salvatore | Nitti, Donato

Article Type: Research Article

Abstract: Tumour microsatellite instability (MSI) is useful in identifying patients with hereditary non-polyposis colorectal cancer (HNPCC) with defective DNA mismatch repair (MMR} genes. A reference Bethesda panel has limitations resulting from the inclusion of dinucleotide markers, which are less sensitive and specific for detection of tumours with MMR deficiencies. We developed a multiplex PCR assay with additional four mononucleotide markers and one dinucleotide marker (NR-21, NR-24, BAT-40, TGF-BetaR and D18S58) for a rapid and proper classification of MSI-H, MSI-L and MSS colorectal cancers. Two tetranucleotide markers were added to identify sample mix-ups and/or contamination. Results: all the 44 cases test cases …were in agreement with previous classification except for three cases: one case MSI-H-Bethesda unstable only for dinucleotides markers shifted to MSI-L category and two cases MSI-L-Bethesda unstable for mononucleotide markers shifted to MSI-H category. Immunohistochemistry analysis revealed that these two MSI-H cases did not expressed hMLH1 and they were found to be methylated at the MLH1 promoter, while the first one that shifted to MSI-L showed MMR protein expression. Conclusion: a complete panel of ten markers including four dinucleotide and six mononucleotide microsatellites allows accurate evaluation of tumor MSI status. Show more

Keywords: Microsatellite instability, colorectal cancer, mononuclotide repeats

DOI: 10.3233/CBM-2009-0118

Citation: Cancer Biomarkers, vol. 6, no. 1, pp. 49-61, 2010