Autoantibodies to the nucleolar phosphoprotein nucleophosmin in breast cancer patients

Nucleophosmin (NPM) is an estrogen-regulated nucleolar phosphoprotein; a substrate for phosphorylation by p34(cdc2) kinase, protein kinase C, and casein kinase II; and a repressor of the transcriptional regulating activities of the YY1 and IFN regulatory factor-1 transcription factors. We have completed a pilot study to determine whether autoantibodies to NPM are present in breast cancer patients and explored the ability of these autoantibodies to predict recurrence in breast cancer patients. One hundred breast cancer patients were studied: 50 who recurred, and 50 matched for age and length of follow-up but who did not recur. Patients' sera were collected at the times of diagnosis (T1), six months before recurrence (T2), and at recurrence (T3). Recurrent and nonrecurrent patients did not differ in autoantibody levels at the times of diagnosis or recurrence. However, antiNPM autoantibody levels increase significantly between diagnosis and six months before recurrence in recurrent patients, whereas no change occurs over the comparable time period in nonrecurrent patients (repeated measures ANOVA; P = 0.041). At recurrence, the levels return to those seen at diagnosis. The greater the change in levels between T1 and T2, the greater the risk of recurrence within the next 6 months (conditional logistic regression: increase in risk for highest versus lowest tertile of change from T1 to T2; odds ratio, 3.25; 95% confidence interval, 1.04-10.18; P = 0.043). Consistent with the estrogenic/antiestrogenic regulation of the antigen in breast cancer cells, the levels of antiNPM autoantibodies are decreased 6 months before recurrence in patients treated with the antiestrogen tamoxifen (P = 0.012). The association between antiNPM levels and recurrence remained after adjustment for confounding factors. Further study of antiNPM autoantibody levels as a new and simple, intermediate serum biomarker for predicting both the timing of recurrence and monitoring response to endocrine manipulations in breast cancer patients is warranted.