Cancer Biomarkers - Volume 7, issue 6

Authors: Kroeze, S.G.C. | Bijenhof, A.M. | Bosch, J.L.H.R. | Jans, J.J.M.

Article Type: Review Article

Abstract: Purpose: Approximately one-third of all Renal Cell Carcinoma (RCC) patients undergoing a nephrectomy face metastatic disease. The availability of novel therapeutics for metastatic patients underscores the importance of identifying patients at risk of recurrence or patients responding well to specific therapies. Unlike clear cell RCC (ccRCC), information on biomarkers for the papillary subtype (pRCC) remains limited. In this review, we identified tissue markers that are differentially expressed between subtypes and may be of diagnostic use. In addition, markers with promising prognostic power for ccRCC and/or pRCC are described and their clinical value is discussed. Materials and methods: To …identify diagnostic markers that differentiate between pRCC and ccRCC a Pubmed search was performed, limited to original articles published in the English language between 1990 and 2009, using the terms pRCC/papillary RCC/papillary renal cell carcinoma/papillary kidney cancer, biomarker/biomarkers, protein expression, mass spectrometry and immunohistochemistry. Prognostic markers for ccRCC and pRCC were identified using the search terms kidney cancer, renal cell carcinoma, prognostic marker, biomarker and prognosis. Only markers with independent prognostic value in multivariable analysis were included. Results: 25 proteins are differentially expressed between ccRCC and pRCC, reflecting the molecularly distinct nature of these subtypes. 5 of these proteins were externally validated, which shows their diagnostic potential. Whereas 48 biomarkers with independent prognostic power have been identified for ccRCC patients, only CD44, CA9, p53, Ki67 and PCNA have shown prognostic value in multiple studies. Expression of IMP-3 and VEGF-R2 are independent predictors of survival of pRCC patients, although this is shown in single studies. Conclusions: So far 5 validated diagnostic markers are able to differentiate between ccRCC and pRCC. Few independent prognostic markers have been identified for pRCC in single studies, compared to numerous biomarkers identified for the more common ccRCC. Despite the abundance of promising markers for ccRCC, their exact role in clinical decision making still needs to be established through validation studies. Show more

Keywords: Papillary renal cell carcinoma, clear cell renal cell carcinoma, biomarker

DOI: 10.3233/CBM-2010-0195

Citation: Cancer Biomarkers, vol. 7, no. 6, pp. 261-268, 2010

Authors: Hann, Hie-Won | Wang, Mengjun | Hafner, Julie | Long, Ronald E. | Kim, Su Hee | Ahn, Meejin | Park, Susan | Comunale, Mary Ann | Block, Timothy M. | Mehta, Anand

Article Type: Research Article

Abstract: In this study, we examined the level of Golgi protein 73 (GP73) in the serum of 9 patients as a function of anti-liver cancer treatment. Although the numbers are small, a clear trend was observed. Patients who remained tumor free (up to 6 years post-treatment) showed reductions in GP73 at the first time point available post-treatment. In contrast, patients who had high levels GP73 post treatment all had re-occurrence within a 5 year period. These data are preliminary but dramatically imply that this marker may have value in the monitoring of HCC patients and may be elevated even when small, …undetectable tumors are present. Show more

DOI: 10.3233/CBM-2010-0190

Citation: Cancer Biomarkers, vol. 7, no. 6, pp. 269-273, 2010

Authors: George, Antony | Ranganathan, Kannan | Rao, Ummadevi Krishna

Article Type: Research Article

Abstract: Introduction: Oral Cancer (OC) is the sixth most common cancer worldwide, while being the most common cancer among Indian males and the third most common cause of their deaths. 70–94% of all the malignancies arising within the oral cavity are oral squamous cell carcinomas (OSCC). Researches show that altered expression of matrix metalloproteinases (MMPs) may have a vital role in regulating the tumor microenvironment of head and neck carcinomas. Aim: To evaluate the expression of MMP-1 in histopathologically different grades of OSCC, to evaluate its expression in normal buccal mucosa (NBM), and to compare the expressions between these …two groups, using the streptavidin horseradish peroxidase biotin labeled immuno-histochemistry (IHC) technique. Result: 100% of OSCC showed cytoplasmic immune reactivity for MMP-1 in the epithelial and connective tissue cells. Their expression was elevated as the histopathological grade differed from well to poorly differentiated. 100% of epithelial cells and 80% of connective tissue of NBM expressed MMP-1.The immune reactivity was significantly over-expressed in OSCC in comparison to NBM. Conclusion: Evidence indicates that the elevated MMP-1 protein expression is associated with higher histopathological grade of OSCC. NBM express MMP-1 diffusely and weakly. MMP-1 immune reactivity increases as OC progresses from NBM to well to poorly differentiated OSCC. Show more

Keywords: Oral cancer, squamous cell carcinoma, matrix metalloproteinase, interstitial collagenase, MMP-1, OSCC

DOI: 10.3233/CBM-2010-0191

Citation: Cancer Biomarkers, vol. 7, no. 6, pp. 275-283, 2010

Authors: von Rahden, Burkhard H.A. | Kircher, S. | Kafka, M. | Stuermer, L. | Reiber, C. | Gattenlöhner, S. | Germer, C.T. | Grimm, M.

Article Type: Research Article

Abstract: Background: Esophageal adenocarcinomas (EACs) arise due to gastroesophageal reflux, with Barrett’s esophagus (BE) regarded as precancerous lesion. Glucocorticoid-induced TNFR family-related Receptor (GITR)-mediated inflammation of tumor infiltrating leucocytes (TILs) in the tumor microenvironment might play a role during the multistep carcinogenetic process as either tumor promoting factor according to an inflammatory microenvironment or as a feature of anti-tumor activity. Methods: Immunohistochemical analysis of GITR expression was analyzed in esophageal cancer (n=70: 41 EAC with BE, 19 EAC without BE, and n=10 esophageal squamous-cell carcinomas, ESCC), the adenocarcinoma cell line OE-33, and peripheral blood leucocytes (PBLs) of EAC patients, furthermore …in biopsies of BE without intraepithelial neoplasia (IN) (n=18). Results were correlated with clinicopathological parameters and five-year survival rates. Immunohistochemical GITR expression results were confirmed on mRNA level (RT-PCR). Results: Quantification showed a significant increase of 25% GITR positive TILs in EAC with BE (p< 0.05) compared to 13% in adjacent BE, 24% in EAC without BE, 14% in ESCC, and 1% in BE without IN. High GITR levels were not significantly associated with clinicopathologic features which may predict worse clinical outcome and had no impact on survival (p= 0.7878). Increased GITR expression of peripheral blood leucocytes (PBLs) in EAC patients was shown on protein level (32%) and confirmed by RT-PCR (3.7-fold difference compared to normal tissue). Conclusions: This study provides for the first time evidence that GITR expression of TILs is associated in the pathogenesis of Barrett’s esophagus. Our findings suggest that GITR-expression of TILs is associated with cancer progression. Its role as either tumor promoting factor %according to an in the inflammatory microenvironment or as a feature of anti-tumor activity and promising target for molecular therapies needs to be substantiated in further investigations. Show more

Keywords: BE, inflammation, carcinogenesis, clinicopathological parameters

DOI: 10.3233/CBM-2010-0192

Citation: Cancer Biomarkers, vol. 7, no. 6, pp. 285-294, 2010

Authors: Yeh, Chen-Hsiung | Abdool, Adam | Bruey, Jean-Marie

Article Type: Research Article

Abstract: In targeted therapy using tyrosine kinase inhibitors (TKIs), measurement of TK activities could be beneficial for diagnosis, identification of potential responders, and monitoring treatment efficacy. Here we evaluated the utility of measuring circulating TK (cTK) activity directly from plasma in leukemia patients positive for the BCR-ABL1. Plasma cTK activity was measured from 46 patients with newly diagnosed chronic myelogenous leukemia (CML), 24 with multidrug-resistant CML, 24 with BCR-ABL1-positive acute lymphocytic leukemia (ALL), and 38 healthy donors. Circulating TK activity was significantly higher in CML (median 801.93 U/mL, range 18.10–3932.30 U/mL) and BCR-ABL1-positive ALL patients (median 659.55 U/mL, range 0–1626.90 U/mL) …than in healthy donors (median 82.85 U/mL, range 0.63–852.80 U/mL) (P < 0.001). Plasma cTK activity was closely correlated with cellular BCR-ABL1 kinase activation as indicated by phosphorylation of the downstream signaling proteins CRKL (P < 0.001) and STAT-5 (P= 0.003). However, cTK activity was not associated with BCR-ABL1 transcript level and was independent of BCR-ABL1 mutation type. Ex vivo inhibition of imatinib and dasatinib on plasma cTK activity was severely diminished in patients harboring T315I mutation. Ex vivo testing measuring the effect of TKIs on plasma cTK activity thus hold promise as drug sensitivity tests for predicting and monitoring response to specific TKIs. Show more

Keywords: Circulating, tyrosine kinase activity, BCR-ABL1, biomarker, targeted therapy

DOI: 10.3233/CBM-2010-0193

Citation: Cancer Biomarkers, vol. 7, no. 6, pp. 295-303, 2010

Authors: Khangarot, Shyamveer Singh | Gupta, Nikhil | Goswami, Binita | Hadke, Niladhar Shankarrao | Lal, Pawanindra | Gupta, Naresh | Khurana, Nita

Article Type: Research Article

Abstract: Introduction: There is evidence that the components of the coagulation/fibrinolytic system play a role in cancer biology and angiogenesis. Studies reveal that at the time of diagnosis, majority of the cancer patients have laboratory evidence of systemic coagulation activation. Our purpose was to investigate the significance of D-Dimer (product of fibrin degradation) and factor VIII levels in breast cancer and to evaluate its relationship with other variables such as histological characteristics, lymph node status and immunohistochemistry markers (ER, PR and Her-2neu). Materials and methods: A prospective study was conducted in the Department of Surgery in collaboration with Departments …of Medicine, Pathology and Radiodiagnosis & Imaging, Maulana Azad Medical College & Lok Nayak Hospital, New Delhi. Fifty patients with diagnosed cancer breast who were treated in surgery department were evaluated for D Dimer and factor VIII levels. D-dimer and Factor VIII levels were measured three times i.e. at the time of commencement of treatment then after three cycles of Chemotherapy (CAF Regimen) and finally after six weeks of surgery. Results: Significantly higher levels of D Dimer and factor VIII were observed in tumors with significant lymphovascular and adipose tissue invasion in comparison to localized tumors. The reduction in D-dimer and Factor VIII values after Surgery was significant for both D-dimer (p value 0.000) and Factor VIII (p value 0.000). The reduction in D-dimer after 3 cycles of chemotherapy was significant for D-dimer (575.51 ± 572.47 ng/ml vs. 422.45 ± 363.58 ng/ml; p value 0.046) but not significant for Factor VIII (307.83 ± 184.47 ng/ml vs. 288.78 ± 163.02 ng/ml; p value 0.151). Conclusion: D-dimer and factor VIII may be used as yardstick for systemic adjuvant therapy in node negative < 1 cm breast cancer. D-dimer may prove to be a safe, convenient and easily available biomarker which can be combined with conventional sentinel node biopsy in clinically node negative breast cancer to assess metastatic disease in axilla and reduce false negative results. Show more

Keywords: D-dimer, breast cancer, Factor VIII, coagulation, chemotherapy

DOI: 10.3233/CBM-2010-0196

Citation: Cancer Biomarkers, vol. 7, no. 6, pp. 305-314, 2010