Seventeen percent of Luminal HER2-negative breast tumors were classified differently depending on whether MIB1 or SP6 antibodies were used for Ki-67 assessment, according to a recent study.
Ki-67 assessment is routinely applied in breast carcinoma to aid tumor classification, prognostic assessment, and treatment planning, but variability in immunohistochemical scoring has limited its broader use. Contributing factors include specimen processing, scoring methodology, and antibody selection. MIB1 is the most used antibody clone, while SP6 is also employed in some laboratories. This study, published in Annals of Diagnostic Pathology, compared the performance of MIB1 and SP6 in Ki-67 assessment and evaluated their potential impact on molecular subtyping in breast carcinoma.
Formalin-fixed, paraffin-embedded tissue blocks from 35 primary breast carcinoma cases were analyzed. Serial sections were stained with MIB1 and SP6 antibodies, and proliferative indices were determined according to the updated recommendations of the International Ki-67 in Breast Cancer Working Group. Tumor type, histologic grade, hormone receptor status, and HER2 status were also assessed. Statistical analysis included Pearson correlation, paired t-test, Welch’s ANOVA, and McNemar’s test.
A significant correlation was observed between Ki-67 indices obtained with MIB1 and SP6 (r = 0.755, p < 0.001). The mean proliferative indices did not differ significantly between clones (p = 0.288). Both antibodies showed a significant association with tumor grade (MIB1: p = 0.003; SP6: p = 0.002). Among Luminal HER2-negative tumors, 17 percent demonstrated discordant molecular subtyping between MIB1 and SP6 when applying a 20 percent proliferative index cut-off. Similar discrepancies were noted when 14 percent and 25 percent thresholds were used, indicating that antibody choice may affect classification of Luminal A versus Luminal B (HER2-negative) tumors.
The results indicate that MIB1 and SP6 provide comparable Ki-67 assessment overall, but differences in individual cases may influence surrogate molecular subtyping. Reporting the antibody clone used in Ki-67 immunohistochemistry may assist in interpreting results across laboratories. Further studies with larger sample sizes are needed to validate whether antibody-specific cut-offs are warranted.
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