ASSOCIATION OF TOLL-LIKE RECEPTOR 9 EXPRESSION WITH PROGNOSIS IN BREAST CARCINOMA

Yıl 2023, Cilt: 13 Sayı: 4, 676 - 681, 31.07.2023

Zeliha Esin Çelik Fatih Demir Harun Yonar Murat Çelik Orhan Önder Eren

https://doi.org/10.16899/jcm.1315131

Öz

Aim:
Breast cancer (BC) is a common malignancy in women. Some molecules including TLR9 are still under investigation as potential prognostic factors in BC. In the present study, we aimed to determine the relation between TLR9 expression and clinicopathological prognostic parameters and survival in BC.

Materials and methods:
One hundred and thirty nine patients diagnosed as BC included the present study. Immuno-reactivity scoring (IRS) system was used to reveal the tissue TLR9 expression levels.

Results:
We found higher TLR9 expression in tumors diagnosed as invasive carcinoma NOS, grade 3 tumors, tumors with necrosis, ER negative and Her2 positive tumors and tripple negative molecular subtype. Furthermore, tumors with low TLR9 scores showed increased overall survival compared to tumors with high TLR9 scores.

Conclusions:
TLR9 overexpression in BC is associated with some prognostic parameters including histologic type, tumor grade, tumor necrosis, ER and Her2 status and molecular subtype as well as overall survival. Further studies with larger patient series are needed to shed light on the use of TLR9 as a clinical and therapeutic target in BC.

Anahtar Kelimeler

breast cancer, pathology, TLR9, İmmunohistochemistry, prognosis

Destekleyen Kurum

Selcuk University Coordinatorship of Scientific Research Projects

Proje Numarası

21401054

MEME KARSİNOMLARINDA TOLL-LİKE RESEPTÖR 9 EKSPRESYONUNUN PROGNOZLA İLİŞKİSİ

Öz

Amaç:
Meme kanseri (MK) kadınlarda sık görülen bir malignitedir. Toll-like reseptör 9 (TLR9) dahil bazı moleküller, MK'de potansiyel prognostik faktörler olarak halen araştırılmaktadır. Bu çalışmada, MK'de TLR9 ekspresyonu ile klinikopatolojik prognostik parametreler ve sağkalım arasındaki ilişkiyi belirlemeyi amaçladık.

Gereç ve Yöntem:
Bu çalışmaya BC tanısı konulan 139 hasta dahil edildi. Doku TLR9 ekspresyon seviyelerini ortaya koymak için immüno-reaktivite skorlama (IRS) sistemi kullanıldı.

Bulgular:
İnvaziv karsinom NOS tanısı alan tümörlerde, derece 3 tümörlerde, nekrozlu tümörlerde, Östrojen reseptörü (ER) negatif ve Human epidermal growth factor 2 (Her2) pozitif tümörlerde ve üçlü negatif moleküler alt tipte daha yüksek TLR9 ekspresyonu bulduk. Ayrıca, TLR9 skorları düşük olan tümörler, yüksek TLR9 skorları olan tümörlere kıyasla daha yüksek genel sağkalım göstermiştir.

Sonuç:
MK'de TLR9 aşırı ekspresyonu, genel sağkalımın yanı sıra histolojik tip, tümör derecesi, tümör nekrozu, ER ve Her2 durumu ve moleküler alt tip gibi bazı prognostik parametrelerle ilişkilidir. TLR9'un MK'de klinik ve terapötik bir hedef olarak kullanımına ışık tutmak için daha geniş hasta serileri ile daha fazla çalışmaya ihtiyaç vardır.

Anahtar Kelimeler

meme kanseri, patoloji, TLR9, immunohistokimya, prognoz

Proje Numarası

21401054

Kaynakça

• 1. Ates O, Gedik E, Sunar V, Altundag K. Serum endocan level and its prognostic significance in breast cancer patients. Journal of Oncological Sciences 2018;4:15–18.
• 2. Kontzoglou K, Palla V, Karaolanis G et al. Correlation between Ki67 and breast cancer prognosis. Oncology 2013;84: 219–225.
• 3. González-Reyes S, Marín L, González L et al. Study of TLR3, TLR4 and TLR9 in breast carcinomas and their association with metastasis. BMC Cancer 2010,10:665.
• 4. Meseure D, Vacher S, Drak Alsibai K et al. Biopathological Significance of TLR9 Expression in Cancer Cells and Tumor Microenvironment Across Invasive Breast Carcinomas Subtypes. Cancer Microenvironment 2016;9:107–18.
• 5. Jukkola-Vuorinen A, Rahko E, Vuopala KS et al. Toll-like Receptor-9 Expression Is Inversely Correlated with Estrogen Receptor Status in Breast Cancer. Journal of Innate Immunity 2008; (1): 59– 68.
• 6. Sandholm J, Selander KS. Toll-like receptor 9 in breast cancer. Frontiers in Immunology 2014;5:330,1-6
• 7. Pasare C, Medzhitov R. Toll-like receptors and acquired immunity. Semin Immunol 2004;16:23-26.
• 8. Wang W, Qiu J, Liu Z et al. Overexpression of RING box protein 1 (RBX1) associated with poor prognosis of nonmuscle-invasive bladder transitional cell carcinoma. J Surg Oncol 2013;107:758–61.
• 9. Costantini S, Capone F, Guerriero E, Castello G. An approach for understanding the inflammation and cancer relationship. Immunol Lett 2009;22:126(1-2):91-2.
• 10. Khatami M. Developmental phases of inflammation-induced massive lymphoid hyperplasia and extensive changes in epithelium in an experimental model of allergy: implications for a direct link between inflammation and carcinogenesis. Am J Ther 2005;12:117-126.
• 11. Manna E. Toll-like Receptor: Breast Cancer Development and Immunotherapy. Arch Can Res. 2016; 4: 3.
• 12. Bhattacharya D, Yusuf N. Expression of toll-like receptors on breast tumors: taking a toll on tumor microenvironment. Int J Breast Cancer. 2012;2012:716564.
• 13. Qiu J, Shao S, Yang G, Shen Z, Zhang Y. Association of Toll like receptor 9 expression with lymph node metastasis in human breast cancer. Neoplasma 2011;58:251-55.
• 14. Merrell MA, Ilvesaro JM, Lehtonen N et al. Toll-like receptor 9 agonists promote cellular invasion by increasing matrix metalloproteinase activity. Mol Cancer Res 2006; 4: 437-47. 15. Hughes GC, Thomas S, Li C et al. Cutting edge: progesterone regulates IFN-α production by plasmacytoid dendritic cells. J Immunol 2008;180: 2029–33. 16. Tuomela J, Sandholm J, Karihtala P et al. Low TLR9 expression defines an aggressive subtype of triple-negative breast cancer. Breast Cancer Res Treat 2012;135:481–93.