Serologic laboratory findings in malignancy.

Serologic findings such as antinuclear antibodies (ANA), usually found in systemic rheumatic diseases, have been known for decades to occur in patients with various cancers.1,2 These and other early reports on ANAs in cancer sera3–8 and the remarkable work responsible for the well-recognized value of autoantibodies for the diagnosis of autoimmune diseases (ADs) such as systemic lupus erythematosus (SLE), scleroderma, and dermatomyositis (DM)/polymyositis (PM)9–13 suggested that autoantibodies could also be potential diagnostic and prognostic biomarkers for cancer. Biomarker discovery using genomics14–21 and proteomics22,23 led to the identification of a multitude of autoantibodies in various types of cancer, some of which appeared to be potential biomarkers for the diagnosis and prognosis of cancer.16–21 Other approaches using antigens known to be involved in carcinogenesis showed that autoantibodies can also be used as potential diagnostic biomarkers.24–26 However, ANAs in cancer sera were for a long time regarded as epiphenomena without any clinical significance. The interpretation of the significance of autoantibodies in cancer sera remained controversial, because although there are examples of autoantibodies commonly found in the ADs such as anti-DNA, anti-Sm, anti-RNP, and other antibodies, 27–31 a large number of the autoantibodies found in cancer sera do not recognize the autoantigens classically associated with the ADs.15–17,22 These conflicting data were generally interpreted as an indication of the nonspecificity of autoantibodies in cancer sera. However, exceptions were known to occur, and a relatively small but steadily increasing group of autoantibodies recognizing the same antigens have been reported in both cancer and autoimmune sera. It is well known that patients with cancer may develop rheumatic, neurologic, and other symptoms generally thought to result from reactivity of autoantibodies with autoantigens located in tissues other than the primary tumor. The discussion of the clinical features as well as the serologic findings in cancer patients with paraneoplastic syndromes,32–34 as well as those in cancer developing in patients with rheumatic diseases,35–38 are outside of the scope of this review. Space limitations preclude the discussion of other important serologic findings in cancer sera, such as the cytokines, which have been covered in several publications.39–41 This review discusses serologic laboratory findings in malignancy of interest to rheumatologists as well as oncologists, from both the practical and basic viewpoints. Because of the potential significance of the use of autoantibodies for the screening and diagnosis of solid tumors, the article reviews primarily the work intending to identify diagnostic biomarkers for cancer and the number of autoantibodies common to the systemic ADs and cancer. Hundreds of autoantibodies recognizing tumor-associated antigens (TAAs) have been reported and reviewed in the past, and by necessity their discussion in this review is limited. The serologic findings in the sera of patients with solid tumors and hematological malignancies that the clinician may encounter in the practice of medicine are also reviewed. Finally, in view of the provocative recent data on the diagnostic and prognostic value of autoantibodies in cancer sera obtained using genomics and proteomics methodologies and the increasing recognition of an important role of B cells in the anticancer immune response,42–47 the potential significance of the prominent autoantibody response in cancer sera is discussed.