Assessment of Anti-Nuclear Antibodies and Anti-Extractable Nuclear Antigen Levels in Breast Cancer Patients

Öz

Anti-nuclear antibodies (ANAs) are autoantibodies synthesized in response to the cell nucleus contents and use as biomarkers of systemic autoimmune diseases. Inflammation, apoptosis and necrosis of the cells are consequences that accompany breast cancer against which autoantibodies will be produced. In this study, we aimed to evaluate the presence of ANAs and anti-extractable nuclear antigens (anti-ENAs) in breast cancer. A total of 33 luminal A and luminal B breast cancer patients were assessed for presence of ANAs and anti-ENAs. All the patients had received hormone therapy at least for 6 months before the tests. Patients were screened to ANAs by indirect immunofluorescence on human epithelial type 2 (HEp-2) cells. AESKUBLOTS® ANA-17 comp kit was used to identify the concentrations of U1-snRNP, snRNP/Sm, SmD1, dsDNA, SS-A/Ro 60, SS-A/Ro 52, SS-B/La antibodies. Fifteen (45.5%) patients were luminal A and 18 (54.5%) patients were luminal B. The median of age was 57 and the median of tumor size was 25. 19 (57.6%) patients had grade I or II and 14 (42.4%) had grade III. 3 patients had ANAs test positive. All the patients who had positive ANA test were luminal A breast cancer and had grade I or II tumors and positive lymph node, whereas, pathological tumor stage were varied. No statistically significant association was found between ANAs positivity and molecular subtype, age, body mass index (BMI), grade, tumor stage or lymph node involvement. Moreover, there were negative correlations between the anti-U1-snRNP and anti-dsDNA with Ki-67 and a correlation between anti-snRNP/Sm and anti-SS-A/Ro 52 was found. Comparing with luminal A, anti-U1-snRNP and anti-snRNP/Sm concentrations were statistically significantly lower in luminal B tumors (p= 0.015 and 0.016 respectively). Patients who had high grade tumors showed low concentrations of anti-snRNP/Sm (p=0.027), whereas patients who had lymph node metastasis showed high concentrations of anti-U1-snRNP (p=0.031). ANAs positivity was more common in luminal A breast cancer patients compared with luminal B. Anti-U1-snRNP and anti-snRNP/Sm concentrations were lower in luminal B. Moreover, patients who had high grade tumors showed low concentrations of anti-snRNP/Sm, whereas those who had lymph node metastasis showed high concentrations of anti-U1-snRNP.

Anahtar Kelimeler

• Anti-nuclear antibodies (ANAs)
• Autoantibodies
• Breast Cancer
• Anti-Extractable Nuclear Antigens (ENAs)

Destekleyen Kurum

İstanbul University and Biruni University. I appreciate your timely review and decision on this manuscript. Yours sincerely,

Etik Beyan

I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. All the authors listed have approved the manuscript that is enclosed.

Teşekkür

Thank you and best regards.

Assessment of Anti-Nuclear Antibodies and Anti-Extractable Nuclear Antigen Levels in Breast Cancer Patients

Öz

Anti-nükleer antikorlar (ANAs), hücre çekirdek içeriğine karşı üretilen otoantikorlardır ve sistemik otoimmün hastalıkların biyobelirteçleri olarak kullanılırlar. İnflamasyon, apoptoz ve hücre nekrozu, meme kanseri ile ilişkili olarak ortaya çıkan hücresel sonuçlardır ve bu duruma karşı otoantikorlar üretilebilir. Bu çalışmada, meme kanserinde ANA'ların ve anti-ekstrakte edilebilir nükleer antijenlerin (anti-ENAs) varlığını değerlendirmeyi amaçladık. Toplam 33 lümenal A ve lümenal B meme kanseri hastası, ANA'ların ve anti-ENAs'ın varlığı açısından değerlendirildi. Tüm hastalar, testlerden en az 6 ay önce hormon terapisi almışlardır. Hastalar, insan epitel tip 2 (HEp-2) hücrelerinde endirekt immünoflorasansta ANA'lar için taranmıştır. U1-snRNP, snRNP/Sm, SmD1, dsDNA, SS-A/Ro 60, SS-A/Ro 52, SS-B/La antikor konsantrasyonlarını belirlemek için AESKUBLOTS® ANA-17 comp kiti kullanıldı. Onbeş hastanın (%45.5) lümenal A ve 18 hastanın (%54.5) lümenal B olduğu belirlendi. Ortalama yaş 57, tümör boyutu ise 25 tir. Hastaların %57.6'sında I veya II derece, %42.4'ünde III derece tümör vardı ve üç hasta ANA testi pozitifti. Pozitif ANA testi olan tüm hastalar lümenal A meme kanserliydi ve I veya II derece tümöre sahip olup pozitif lenf noduna sahipti; ancak patolojik tümör evresi değişkenlik gösteriyordu. ANA pozitifliği ile moleküler alt tip, yaş, vücut kitle indeksi (VKİ), derece, tümör evresi veya lenf nodu tutulumu arasında istatistiksel olarak anlamlı bir ilişki bulunamamıştır. Ayrıca, anti-U1-snRNP ve anti-dsDNA'nın Ki-67 ile negatif, anti-snRNP/Sm ve anti-SS-A/Ro 52'nin ise pozitif bir korelasyonu bulunmuştur. Lümenal A ile karşılaştırıldığında, anti-U1-snRNP ve anti-snRNP/Sm konsantrasyonları lümenal B tümörlerinde istatistiksel olarak önemli ölçüde düşük bulunmuştur (sırasıyla p= 0.015 ve 0.016). Yüksek dereceli tümöre sahip hastalar, düşük anti-snRNP/Sm konsantrasyonları gösterirken, lenf nodu metastazına sahip olanlar yüksek anti-U1-snRNP konsantrasyonları sergilemiştir (sırasıyla p=0.027 ve 0.031). ANA pozitifliği, lümenal A meme kanseri hastalarında lümenal B'ye kıyasla daha yaygın bulunmuştur. Anti-U1-snRNP ve anti-snRNP/Sm konsantrasyonları lümenal B'de daha düşüktür. Ayrıca, yüksek dereceli tümöre sahip hastalar düşük anti-snRNP/Sm konsantrasyonları gösterirken, lenf nodu metastazı olanlar yüksek anti-U1-snRNP konsantrasyonları sergilemiştir.

Anahtar Kelimeler

• Anti-nükleer antikorlar (ANAs)
• Otoantikorlar
• Meme Kanseri
• Anti-Çekilebilir Nükleer
• Antijenler (ENAs)

Kaynakça

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