Decreased Serum and Tissue Levels of Isthmin-1 in Patients With Idiopathic Granulomatous Mastitis: A Case-Control Study.

Background: Idiopathic granulomatous mastitis (IGM) is a chronic inflammatory breast disorder with unclear etiology. Isthmin-1 (ISM1), a secreted protein with anti-inflammatory properties, has not been previously studied in IGM. Objective: This study aimed to compare serum and tissue ISM1 levels between IGM patients and healthy controls, and to assess its diagnostic potential. Methods: This case-control study included 30 women with histopathologically confirmed IGM and 30 age-matched controls undergoing breast reduction surgery. Serum and tissue ISM1 levels were measured using ELISA. Receiver operating characteristic (ROC) analysis assessed the diagnostic performance of serum ISM1. Results: ISM1 concentrations were significantly lower in IGM patients compared to controls in both serum (541.42 ± 191.01 vs. 1139.19 ± 698.43 pg/mL; p = 0.019) and tissue (511.07 ± 188.16 vs. 778.24 ± 261.98 pg/mL; p  < 0.001). ROC analysis demonstrated moderate diagnostic accuracy (area under the curve [AUC]: 0.768, 95% CI: 0.651-0.885; optimal cutoff: 676.13 pg/mL; sensitivity: 66.7%; specificity: 83.7%). Standard inflammatory markers showed no significant differences between groups. Conclusions: Reduced ISM1 levels in IGM patients suggest potential involvement in disease pathogenesis. While serum ISM1 shows promise as a supportive biomarker, larger studies, including other inflammatory breast conditions, are needed to confirm specificity and clinical utility.