Douglas D Taylor1, Safinur Atay, Daniel S Metzinger, Cicek Gercel-Taylor. 1. Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Women's Health, University of Louisville School of Medicine, Louisville, KY 40292, USA. ddtaylor@louisville.edu
Abstract
OBJECTIVES: Current antigen-based diagnostic assays for ovarian cancers rely on intravasation of specific aberrantly expressed proteins and their achieving detectable steady-state concentrations, resulting in their inability to truly detect small early lesions. In contrast, tumor antigen immunorecognition is observed following initial transformation events. Our objective was to characterize humoral antitumor responses in terms of IgG subclasses generated and tumor antigens recognized. METHODS: For patients with benign and malignant ovarian disease, tumor-reactive IgG subclasses were characterized by Western immunoblotting. Antigen recognition patterns were analyzed by 2-dimensional electrophoresis and proteins exhibiting shared or stage-specific recognition were defined by mass spectrometry (MS) sequencing. RESULTS: Sera from ovarian cancer patients exhibited significantly greater immunoreactivities than either controls or women with benign disease. While late-stage patients recognized more proteins at greater intensity, stage-specific differential recognition patterns were observed in the IgG subclasses, with the greatest recognition appearing in IgG2 subclasses. Immunoreactivity in IgG2 and IgG3 from stage I and II patients appears to be most intense with nuclear antigens >40 kDa, while, in stage III patients, additional immunoreactivity was present in the <40 kDa components. Stage III patients also exhibited similar reaction with membrane antigens <40 kDa. Two-dimensional electrophoresis revealed 32 stage-linked antigenic differences with 11 in early-stage and 21 in late-stage ovarian cancer. CONCLUSIONS: Owing to the timing and stability of humoral responses, quantitation of IgG subclasses recognizing specific tumor antigens provides superior biomarkers for early cancer identification and allows for differentiation of benign versus malignant ovarian masses and early- and late-stage cancers. Copyright 2009 Elsevier Inc. All rights reserved.
OBJECTIVES: Current antigen-based diagnostic assays for ovarian cancers rely on intravasation of specific aberrantly expressed proteins and their achieving detectable steady-state concentrations, resulting in their inability to truly detect small early lesions. In contrast, tumor antigen immunorecognition is observed following initial transformation events. Our objective was to characterize humoral antitumor responses in terms of IgG subclasses generated and tumor antigens recognized. METHODS: For patients with benign and malignant ovarian disease, tumor-reactive IgG subclasses were characterized by Western immunoblotting. Antigen recognition patterns were analyzed by 2-dimensional electrophoresis and proteins exhibiting shared or stage-specific recognition were defined by mass spectrometry (MS) sequencing. RESULTS: Sera from ovarian cancerpatients exhibited significantly greater immunoreactivities than either controls or women with benign disease. While late-stage patients recognized more proteins at greater intensity, stage-specific differential recognition patterns were observed in the IgG subclasses, with the greatest recognition appearing in IgG2 subclasses. Immunoreactivity in IgG2 and IgG3 from stage I and II patients appears to be most intense with nuclear antigens >40 kDa, while, in stage III patients, additional immunoreactivity was present in the <40 kDa components. Stage III patients also exhibited similar reaction with membrane antigens <40 kDa. Two-dimensional electrophoresis revealed 32 stage-linked antigenic differences with 11 in early-stage and 21 in late-stage ovarian cancer. CONCLUSIONS: Owing to the timing and stability of humoral responses, quantitation of IgG subclasses recognizing specific tumor antigens provides superior biomarkers for early cancer identification and allows for differentiation of benign versus malignant ovarian masses and early- and late-stage cancers. Copyright 2009 Elsevier Inc. All rights reserved.
Authors: Dan Lu; Elisabetta Kuhn; Robert E Bristow; Robert L Giuntoli; Susanne Krüger Kjær; Ie-Ming Shih; Richard B S Roden Journal: Gynecol Oncol Date: 2011-06-24 Impact factor: 5.482
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