Showing papers by "Eng M. Tan published in 2003"

Recursive Partitioning as an Approach to Selection of Immune Markers for Tumor Diagnosis

Abstract: Purpose and Experimental Design: Cancer sera contain antibodies which react with a unique group of autologous cellular antigens called tumor-associated antigens (TAAs), but the low frequency of positive reactions against any individual antigen has precluded use of autoantibodies as useful diagnostic markers. With enzyme immunoassay, we examined antibody frequencies to a panel of seven TAAs, c-myc, cyclin B1, IMP1, Koc, p53, p62, and survivin, in 527 cancer patients (64 breast cancer patients, 45 colorectal cancers, 91 gastric cancers, 65 hepatocellular carcinomas, 56 lung cancers, and 206 prostate cancers), and 346 normals. We used recursive partitioning to assess whether we could accurately classify individuals as either cancer patients or normals on the basis of the profile of antibody reactivity to the seven TAAs for each individual. Results: Recursive partitioning resulted in the selection of subsets of the seven-panel TAA, which differentiated between tumors and controls, and these subsets were unique to each cancer cohort. The classification trees had sensitivities ranging from 0.77 to 0.92 and specificities ranging from 0.85 to 0.91 in the cancer cohorts when normal means +2 SDs were used as standard cutoffs for immunoassay positivity. Antibody to cyclin B1 was the initial discriminating node for gastric and lung cancers, and for hepatocellular carcinoma, and was a subsequent discriminating node in all of the other cancer cohorts. c-myc was the initial discriminating node in breast cancer, p62 in prostate cancer, and IMP1 in colon cancer. Recursive partitioning demonstrated that no more than three of the seven TAAs were needed for any cancer cohort to arrive at these levels of sensitivity and specificity. Conclusions: This initial study shows that multiple antigen miniarrays can provide accurate and valuable tools for cancer detection and diagnosis. Performance of the miniarrays might be enhanced by other combinations of TAAs appropriately selected for different cancer cohorts.

Relative paradigms between autoantibodies in lupus and autoantibodies in cancer.

Abstract: Autoantibodies which are reactive with intracellular antigens have been studied extensively in autoimmune rheumatic diseases such as systemic lupus erythematosus (lupus), Sjogren's syndrome, scleroderma, dermatomyositis/polymyositis, and other related diseases [1]. Autoantibodies are being recognized with increasing frequency in other illnesses including type I diabetes [2], the paraneoplastic neurological disease syndromes [3,4], liver diseases [5], bullous skin diseases, inflammatory bowel diseases, thyroid and other endocrinopathies, haematopoietic disorders and many others [6]. Autoantibody to p53 was detected in breast cancer [7] but for a time the main interest was in T cell-mediated autoimmunity [8], until it became evident that humoral immunity was also a prominent response in many different types of cancer [9–11]. In this paper, we will review and discuss the special features of spontaneously occurring autoantibodies and in the case of cancer, how some patients’ immune systems appear to be sensing aberrant cellular mechanisms related to tumorigenesis and reporting these events in the form of the contemporaneous appearance of neo-antibodies. There are some similarities between autoantibodies in lupus (and other autoimmune diseases) and autoantibodies in cancer and there are some differences, but important insights into aetiology, pathogenesis and therapeutic strategies could be gained by careful analysis of the deeper implications of autoimmune responses in both lupus and cancer.