Autoimmunity To Cenpf In Cancer

Although the clinical significance of anti-CENP-F autoantibodies still needs to be further investigated, the available evidence indicates that autoimmunity to this protein is likely to be associated with the presence of a malignant tumor. An evaluation of the clinical histories of 26 patients producing anti-CENP-F IgG antibodies revealed that 14 (54%) of these patients had cancers of various types [20], Some of the non-cancer patients had conditions associated with ab-

normal or increased cell proliferation such as hepatitis B and C-associated chronic liver disease. Interestingly, the average IIF titer of the anti-CENP-F antibodies in the patients with cancer, 1:10,103, was significantly higher than the average titer in the noncancer patients, 1:3,200 (p = 0.008), indicative of a vigorous immune response to CENP-F in the antibody-positive cancer patients. A more recent study extended the characterization of the 26 anti-CENP-F positive sera and added an additional group of 10 CENP-F antibody-positive patients [21]. This new group included 8 patients with cancer. In total, 22 (61%) of these individuals had cancer, with breast (9 out of 22) and lung (5 out of 22) neoplasms being the most common malignancies. The presence of anti-CENP-F autoantibodies did not appear to be associated with systemic autoimmunity since only 4 of the 36 patients were diagnosed with systemic rheumatic diseases and the antibodies were not detected by IIF in large numbers of patients with systemic autoimmunity [20, 21]. Tables 1 and 2 summarize the clinical data of patients with circulating autoantibodies to CENP-F for which a diagnosis is known.

It is unclear whether the appearance of antibodies to CENP-F antedates the clinical appearance of cancer. It would be important to follow prospectively CENP-F antibody-positive patients with no cancer history and assess whether their clinical status might change to a malignant condition. Of particular interest would be patients with disease conditions, such as hepatitis B- and C-associated chronic liver disease, that may develop with time into malignancy.

It should be emphasized that although the majority of patients producing autoantibodies to CENP-F have cancer, the frequency of these autoantibodies in un-selected cancer populations is rare when detected by IIF. For instance, a survey of 10 patients with small-cell lung carcinoma, 50 patients with breast cancer, and 50 patients with malignant melanoma by IF in HEp-2 cells did not reveal antibodies to CENP-F [21], More extensive surveys involving 204 patients with hepatocellular carcinoma and 1,365 patients with various solid tumors yielded a frequency of anti-CENP-F autoantibodies of less than 1% [9, 10]. This low frequency of anti-CENP-F antibodies in unselected cancer patients, which should be confirmed by other detection methods, raises questions concerning the association of these autoantibodies with malignancy. Although the presence of these autoantibodies might be indicative of an underlying tumor, it can not be ruled out that autoimmunity to CENP-F may be linked not to tumor development but to a specific cancer-associated condition or treatment, or perhaps other clinical conditions shared by anti-CENP-F-positive patients. It is therefore of paramount importance to follow closely in different centers the clinical evolution of patients that are positive for anti-CENP-F autoantibodies.

Epitope mapping studies in which anti-CENP-F-positive sera were reacted with recombinant polypeptides corresponding to different regions of the CENP-F molecule indicated a correlation between the presence of cancer and preferential antibody reactivity with epitopes in the C-terminal portion [21], an important region for CENP-F function. Although the biological significance of this observation is still unclear, it should be noted that in general autoantibodies are preferentially directed against highly conserved and functional regions of proteins [11].

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