Review Article

Autoantibodies to Tailor-Made Panels of Tumor-Associated Antigens in Breast Carcinoma

Table 1

AAb assays to tailor-made panels of TAAs in breast carcinoma.

Panel of TAAsSerum samplesResults of AAb assayCommentReference

p53, c-myc, HER2, NY-ESO-1, BRCA2, and MUC197 IBC patients (mean age, ), 40 DCIS patients (mean age, ), and 94 controls (50 healthy blood donors and 44 women (mean age, ) with normal mammogram).64% (62/97) of IBC patients and 45% (18/40) of DCIS patients were seropositive for at least one of the six TAAs.
This corresponded to a sensitivity of 64% and 45% for IBC and DCIS, respectively, and specificity of 85% for both IBC and DCIS.
Positive seroreactivity was defined as an ELISA absorbance value greater than the mean + 2 SDs of the normal cohort. No correlation was found with age, tumor size, histologic grade, lymph node status, or detection method. [3]

IMP1, p62, Koc, p53, c-MYC, cyclin B1, and survivin64 IBC Chinese patients, 82 healthy Chinese subjects, 264 healthy USA subjects, 62 SLE USA patients, and 41 SS USA patients.43.8% (28/64) of IBC Chinese patients were seropositive for at least one of the seven TAAs. This was significantly higher ( ) than 11% (9/82) of healthy Chinese subjects and 9.9% (26/264) of healthy USA subjects. Using classification trees based on recursive partitioning yielded a sensitivity of >70%.Positive seroreactivity was defined as an ELISA absorbance value above the mean + 3 SDs of the healthy Chinese subjects. Only 3% (3/62) and 0% (0/41) of SLE and SS patients, respectively, were seropositive. [15, 16]

Discrimination between IBC patients and healthy controls gave a ROC AUC of 0.73 (95% CI, 0.60–0.79) with a sensitivity of 55.2%, a specificity of 87.9%, and a diagnostic accuracy of 75.1%.Definition of positive seroreactivity was not reported. Except for age of DCIS patients, no correlation was found with histologic type and grade, tumor size, lymph node status, and absence or presence of ER, PR and HER-2.
PPIA, PRDX2, FKBP52, HSP-60, and MUC160 early-stage IBC patients, 82 DCIS patients, and 93 matched healthy controls (mean age, 55).Discrimination between DCIS patients of all ages and healthy controls gave a ROC AUC of 0.80 (95% CI, 0.71–0.85) with a sensitivity of 72.2%, a specificity of 72.6%, and a diagnostic accuracy of 72.4%.[17]
Discrimination DCIS patients under 50 years of age and healthy controls gave a ROC AUC of 0.85 (95% CI, 0.61–0.92) with a sensitivity of 73.6%, a specificity of 81.6%, a diagnostic accuracy of 73.4%, a predictive positive value of 67.3%, and a negative predictive value of 85.7%.

MUC1, HER2, p53, and IGFBP2Number of patients and controls was not reported. 18% of patients had early-stage IBC and 82% had late-stage IBC. Age range, 18–75 years. Controls were age- and gender-matched.31% of IBC patients were seropositive for at least one of the four TAAs. Seropositive rate for healthy controls was not reported.Positive seroreactivity was defined as an ELISA absorbance value greater than the mean + 3 SDs of the normal cohort. [1]

p53, HER2, IGFBP-2, and TOPO2α184 late-stage IBC patients (most of them received prior treatment) and 134 healthy controls.Discrimination between IBC patients and healthy controls gave a ROC AUC of 0.63 ( ). Using an algorithm weighted on logistic regression coefficients resulted in an AUC of 0.7 ( ).Positive seroreactivity was defined as an ELISA absorbance value greater than the mean + 3 SDs of the normal cohort. [1]

Survivin and livin46 IBC patients and 10 healthy controls (blood donors).52.2% (24/46) of IBC patients were seropositive for at least one of the two TAAs. Seropositive rate for healthy controls was not reported; however, the difference between IBC patients and healthy controls was reported to be statistically significant ( ).Positive seroreactivity was defined as an ELISA absorbance value greater than the mean + 2 SDs of the normal cohort. No correlation was found with tumor size, lymph node status or distant metastasis. [18]

ASB-9, SERAC1, and RELT87 IBC patients and 87 normal controls.80.4% (70/87) of IBC patients were seropositive for at least one of the three TAAs. Discrimination between IBC patients and healthy controls gave a ROC AUC of 0.861 with a sensitivity of 80% and a specificity of 100% ( ).Definition of positive seroreactivity was not reported. AAbs were measured by phage protein ELISAs. A logistic regression model and leave-one-out validation was used to evaluate predictive accuracies. [19]

p16, p53, and c-myc41 IBC patients and 82 normal controls.43.9% (18/41) of IBC patients and 2.4% (2/82) of normal controls were seropositive for at least one of the three TAAs ( ). This corresponded to a sensitivity of 43.9%, specificity of 97.6%, false negative rate of 56.1%, false positive rate of 2.4%, positive predictive value of 90%, and negative predictive value of 77.7%.Positive seroreactivity was defined as an ELISA absorbance value greater than the mean + 3 SDs of the normal cohort. [20]

AAb: autoantibody; TAA: tumor-associated antigen; IBC: invasive breast carcinoma; DCIS: ductal carcinoma in situ; SD: standard deviation; SLE: systemic lupus erythmatosus; SS: Sjogren's syndrome; ROC: receiver operating characteristic curve; AUC: area under curve; CI: confidence interval; ER: estrogen receptor; PR: progesterone receptor.