Mumps and ovarian cancer: modern interpretation of an historic association

Background Epidemiologic studies found childhood mumps might protect against ovarian cancer. To explain this association, we investigated whether mumps might engender immunity to ovarian cancer through antibodies against the cancer-associated antigen MUC1 abnormally expressed in the inflamed parotid gland. Methods Through various health agencies, we obtained sera from 161 cases with mumps parotitis. Sera were obtained from 194 healthy controls. We used an ELISA to measure anti-MUC1 antibodies and electro-chemiluminescence assays to measure MUC1 and CA 125. Log-transformed measurements were analyzed by t-tests, generalized linear models, and Pearson or Spearman correlations. We also conducted a meta-analysis of all published studies regarding mumps and ovarian cancer. Results Adjusting for assay batch, age, and sex, the level of anti-MUC1 antibodies was significantly higher in mumps cases compared to controls (p = 0.002). Free circulating levels of CA 125, but not MUC1, were also higher in cases (p = 0.02). From the meta-analysis, the pooled odds ratio estimate (and 95% CI) for the mumps and ovarian cancer association was 0.81 (0.68–0.96) (p = 0.01). Conclusion Mumps parotitis may lead to expression and immune recognition of a tumor-associated form of MUC1 and create effective immune surveillance of ovarian cancer cells that express this form of MUC1

Humoral immune response to MUC5AC in patients with colorectal polyps and colorectal carcinoma

BACKGROUND: MUC5AC is a secreted mucin aberrantly expressed by colorectal polyps and carcinoma. It has been hypothesized that aberrant expression of MUC5AC in colorectal carcinoma tissues increased the overall survival of patients with colorectal carcinoma. The present study investigates the incidence of naturally occurring MUC5AC antibodies in the sera of normal individuals, patients with colonic polyps and patients with advanced colorectal carcinoma. A second aim was to determine the relationship of MUC5AC antibody with the prognosis of colorectal carcinoma. METHODS: Free circulating MUC5AC antibodies were measured using an enzyme-linked immunosorbent assay with a synthetic peptide corresponding to an 8 aa. segment of MUC5AC tandem repeat region. Immunohistochemical analysis was completed to demonstrate MUC5AC expression in the polyp specimens. RESULTS: MUC5AC antibodies were detected in 6 of 22 (27.3%) healthy subjects, 9 of 20 (45%) polyp patients, 18 of 30 (60%) patients with colorectal cancer. The presence of circulating free MUC5AC antibody levels was significantly correlated with expression of MUC5AC in polyp sections. Serum MUC5AC antibody positivity was higher in patients with colon located tumors, advanced stage and poorly differentiated tumors were found negatively affecting patient survival in our study. MUC5AC antibody positivity was higher in patients with poor prognostic parameters. Disease free survival and overall survival were shorter in this group of patients. In the multivariate analysis MUC5AC antibody positivity didn't find an independent prognostic factor on prognosis. CONCLUSION: Decreased survival in colorectal carcinoma patients with MUC5AC antibody positivity may be due to a decrease in the MUC5AC expression in tumor tissues of surviving carcinoma patients

Anti-MUC1 Antibody in Nipple Aspirate Fluids Correlates with Tumor Aggressiveness in Breast Cancer: A Feasibility Study

Antibodies against MUC1 are found in circulation of breast cancer (BC) patients. We hypothesized that anti-MUC1 antibodies might be present in even a higher concentration in nipple aspirate fluid (NAF) and could be used to predict aggressiveness of BC. Serum and NAF samples were collected from high risk lesions, BC, and healthy contralateral breasts. ELISA was used to measure the amount of IgG, IgM, and IgA against a tumor-specific MUC1 peptide derived from the extracellular tandem repeat domain of MUC1. Tumor characteristics were recorded prospectively; 120 NAF samples were obtained from a total of 77 women in the study. There was no significant difference of anti-MUC1 antibody levels compared to BC with other lesions. Anti-MUC1 IgG level in NAF was higher in triple negative tumors (P=0.02); serum anti-MUC1 IgG levels were significantly higher in patients with ER (−) tumor and recurrent disease (P=0.01); NAF anti-MUC1 IgA levels were significantly higher in patients with LVI and Her2-neu (+) tumors (P<0.05). These results show that NAF could be a reliable biomarker to predict tumor aggressiveness in BC. A larger study will be needed to confirm these data and to investigate the potential of anti-MUC1 antibodies in NAF and serum to predict disease outcome

Anti-MUC1 Antibodies and Ovarian Cancer Risk: Prospective Data from the Nurses' Health Studies

The surface epithelial glycoprotein MUC1 becomes overexpressed and hypoglycosylated in adenocarcinomas; similar changes occur during nonmalignant inflammatory events. Antibodies developed against tumor-like MUC1 in response to such events could be one way through which ovarian cancer risk factors operate. METHODS: We evaluated the association between anti-MUC1 antibodies and risk of ovarian cancer in a prospective nested case-control study in the Nurses' Health Studies. We used an ELISA to measure plasma anti-MUC1 antibodies in 117 ovarian cancer cases collected at least 3 years before diagnosis and 339 matched controls. RESULTS: In controls, younger women (P-trend = 0.03), those with a tubal ligation (P = 0.03), and those with fewer ovulatory cycles (P-trend = 0.04) had higher antibody levels. In cases, women with late-stage disease (P = 0.04) and those whose specimen was >11 years remote from diagnosis (P = 0.01) had higher antibody levels. Overall, increasing anti-MUC1 antibody levels were associated with a nonsignificant trend for lower risk for ovarian cancer, but there was highly significant heterogeneity by age (P-heterogeneity = 0.005). In women or = 64 years, the corresponding relative risk was 2.11 (95% confidence interval, 0.73-6.04); P-trend = 0.05). CONCLUSION: Anti-MUC1 antibodies evaluated several years before diagnosis may be associated with lower risk of subsequent ovarian cancer in women <64 years old at assessment. IMPACT: Key elements of an "immune model" to explain ovarian cancer risk factors are confirmed and should be evaluated in larger prospective studies.Other Research Uni