İdiyopatik Granülomatöz Mastitiste Tedavi Direncinin Öngörülmesinde Gas6/sAXL Sinyal Yolunun Prognostik Rolü

Abstract

İdiyopatik granülomatöz mastit, etiyopatogenezi tam olarak bilinmeyen ve tedavi yanıtı değişkenlik gösteren nadir kronik inflamatuvar bir meme hastalığıdır. Gas6/sAXL sinyal yolunun immün düzenlemede önemli rol oynadığı bilinmekle birlikte, idiyopatik granülomatöz mastit’deki prognostik değeri henüz araştırılmamıştır. Bu retrospektif gözlemsel kohort çalışmasına histopatolojik olarak doğrulanmış 37 idiyopatik granülomatöz mastit hastası dahil edildi ve hastalar tedaviye yanıtlı (n=18) ve dirençli (n=19) olarak sınıflandırıldı. Ayrıca yaş ve vücut kitle indeksi açısından benzer 17 sağlıklı kontrol değerlendirildi. Tedavi direnci, standart farmakoterapiye rağmen 24 hafta içinde remisyon sağlanamaması veya en az altı haftalık tedavi sonrasında cerrahi müdahale gerektiren apse ya da sinüs traktının ilerlemesi veya devam etmesi olarak tanımlandı. Tedavi öncesi serum ve formalinle fikse parafine gömülü doku örneklerinde Gas6 ve sAXL düzeyleri ELISA yöntemiyle ölçüldü. Ayırt edici performans analizi ile tedavi direncinin bağımsız belirleyicileri ise lojistik regresyon analizi ile değerlendirildi. Serum Gas6 düzeyleri her iki idiyopatik granülomatöz mastit grubunda kontrollere göre anlamlı derecede düşüktü (p<0.001). sAXL düzeyleri yanıtlı grupta anlamlı olarak düşük bulunurken, dirençli grup ile kontroller arasındaki fark Dunn-Bonferroni düzeltmesi sonrası anlamlılığını korumadı. Ayırt edici performans analizinde Gas6 için AUC 0.747 (p=0.003), sAXL için ise 0.727 (p=0.006) bulundu. Gas6 için <1.9 pg/mL eşik değeri tedavi direncini %74 duyarlılık ve %72 özgüllükle öngördü. Çok değişkenli analizde Gas6 <1.9 pg/mL ve apse varlığı tedavi direncinin bağımsız belirleyicileri olarak saptandı. Azalmış Gas6 düzeyleri idiyopatik granülomatöz mastit’de tedavi direnci ile bağımsız ilişkili olup, apse varlığıyla birlikte klinik karar süreçlerinde yararlı biyobelirteçler olabilir.

Keywords

• Biyobelirteç
• Gas6
• idiyopatik granülomatöz mastitis
• sAXL
• tedavi direnci

Prognostic Role of Gas6/sAXL Signaling Pathway in Predicting Treatment Resistance in Idiopathic Granulomatous Mastitis

Abstract

Idiopathic granulomatous mastitis is a rare chronic inflammatory breast disease with unclear pathogenesis and unpredictable therapeutic outcomes. Although the Gas6/sAXL signaling pathway plays an important role in immune regulation, its prognostic significance in idiopathic granulomatous mastitis remains unknown. This retrospective observational cohort study included 37 women with histopathologically confirmed idiopathic granulomatous mastitis, categorized as treatment-responsive (n=18) or treatment-resistant (n=19), and 17 age- and body mass index-matched healthy controls. Treatment resistance was defined as failure to achieve remission within 24 weeks of standard pharmacotherapy, or progression/persistence of abscess or sinus tract requiring surgical intervention after at least six weeks of treatment. Pre-treatment serum and formalin-fixed paraffin-embedded tissue levels of Gas6 and sAXL were measured using enzyme-linked immunosorbent assay. Receiver operating characteristic analysis evaluated discriminatory performance, while binary logistic regression identified independent predictors of treatment resistance. Serum Gas6 levels were significantly lower in both idiopathic granulomatous mastitis subgroups compared with controls (p<0.001). sAXL levels were significantly reduced in the responsive group; however, differences between resistant patients and controls were not significant after Dunn-Bonferroni correction. Receiver operating characteristic analysis demonstrated moderate discriminatory ability for Gas6 (AUC=0.747, p=0.003) and sAXL (AUC=0.727, p=0.006). A Gas6 cutoff value <1.9 pg/mL predicted treatment resistance with 74% sensitivity and 72% specificity. Multivariable analysis identified Gas6 <1.9 pg/mL (OR=5.18, 95% CI: 1.09-24.70, p=0.039) and abscess formation (OR=5.88, 95% CI: 1.14-33.3, p=0.035) as independent predictors of resistance, whereas sAXL lost significance. Reduced Gas6 levels are independently associated with treatment resistance in idiopathic granulomatous mastitis and, together with abscess formation, may serve as clinically useful markers for individualized therapeutic decision-making. Prospective multicenter studies are warranted to validate these findings.

Keywords

• Biomarker
• Gas6
• idiopathic granulomatous mastitis
• sAXL
• treatment resistance

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