Association of Rac1 Expression with Trastuzumab Resistance in HER2-Positive Breast Cancer
Küçük Resim Yok
Tarih
2013
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
HER2’yi aşırı eksprese eden meme kanseri hastalarında birçok moleküler mekanizmanın trastuzumab direnci ile ilişkili olduğu düşü- nülmektedir. Fakat bu mekanizmaların ne kadar aktif olduğu ve hangi sıra ile etki ettiği bilinmemektedir. Bu çalışmada erbB yolağında görevli olan Rac1 and neuregulin 1 (NRG1) adlı proteinlerin HER2-pozitif meme kanserli hastalarda trastuzumab direnci ile ilişkisi araştırılmıştır. Trastuzumab direnci, metastatik meme kanserli hastalarda trastuzumab tedavisinin ilk altı ayında gelişen progresyon olarak tanımlanırken, adjuvan trastuzumab tedavisi alanlarda tedavi tamamlanmadan gelişen lokal nüks veya uzak metastaz olarak tanımlanmıştır. Rac1 ve NRG1 ekspresyonu imünohistokimyasal olarak 22 (n=12 adjuvan, n=10 metastatik) trastuzumab direnç- li ve 27 kontrol hasta dokusunda çalışılmıştır. Rac1, adjuvan trastuzumab dirençli grupta kontrol grubuna göre istatistiksel anlamlı olarak daha yoğun boyanmıştır (p= 0.02). Ayrıca Rac1 açısından tüm dirençli grupla kontrol grubu karşılaştırıldığında, Rac1’in dirençli grupta daha yoğun boyandığı izlenmiştir (p= 0.051). Kontrol grubuna kıyasla dirençli grupta NRG1’in de daha yoğun boyanmasına rağmen, bu fark istatistiksel anlamlılığa ulaşmamıştır (p= 0.09). HER2-pozitif meme kanseri hastalarından adjuvan trastuzumab tedavisi alanlarda, Rac1 pozitişiği erken hastalık nüksü ile ilişkili bulunmuştur. Bu moleküllerin trastuzumab bazlı tedavilerin etkinliği ile olan ilişkisinin aydınlatılması için daha büyük çalışmalara ihiyaç vardır.
Several molecular mechanisms are believed to take role in the development of trastuzumab resistance in breast cancer patients with overexpressing HER2. However, the sequence and the activity of these mechanisms are still unclear. In this study, Rac1 and neuregulin 1 (NRG1), two of ErbB pathway related proteins, were analyzed in HER2-positive breast cancer patients to investigate their roles in trastuzumab resistance. Trastuzumab resistance in metastatic breast cancer treatment was defined as a progression within six months of the treatment and in the adjuvant manner as an occurrence of local/distant recurrence before completion of treatment. Expression of Rac1 and NRG1 by immunohistochemistry (IHC) was studied in all 22 (n=12 adjuvant, n=10 metastatic) trastuzumabresistant and 27 control tissue samples. The staining intensity of Rac1 was statistically significant in adjuvant treatment resistant group when compared with the controls (p= 0.02). In addition, when all resistant groups were compared with the control groups, Rac1 staining intensity was denser (p= 0.051). NRG1 staining intensity was in tendency to be denser as compared to control group, however it did not reach to a statistically significant level (p= 0.09). In HER2-positive breast cancer, presence of Rac1 protein is significantly associated with early response failure to adjuvant trastuzumab therapy. However, further studies with larger groups are warranted to show the value of these molecules in predicting the response to trastuzumab-based therapies.
Several molecular mechanisms are believed to take role in the development of trastuzumab resistance in breast cancer patients with overexpressing HER2. However, the sequence and the activity of these mechanisms are still unclear. In this study, Rac1 and neuregulin 1 (NRG1), two of ErbB pathway related proteins, were analyzed in HER2-positive breast cancer patients to investigate their roles in trastuzumab resistance. Trastuzumab resistance in metastatic breast cancer treatment was defined as a progression within six months of the treatment and in the adjuvant manner as an occurrence of local/distant recurrence before completion of treatment. Expression of Rac1 and NRG1 by immunohistochemistry (IHC) was studied in all 22 (n=12 adjuvant, n=10 metastatic) trastuzumabresistant and 27 control tissue samples. The staining intensity of Rac1 was statistically significant in adjuvant treatment resistant group when compared with the controls (p= 0.02). In addition, when all resistant groups were compared with the control groups, Rac1 staining intensity was denser (p= 0.051). NRG1 staining intensity was in tendency to be denser as compared to control group, however it did not reach to a statistically significant level (p= 0.09). In HER2-positive breast cancer, presence of Rac1 protein is significantly associated with early response failure to adjuvant trastuzumab therapy. However, further studies with larger groups are warranted to show the value of these molecules in predicting the response to trastuzumab-based therapies.
Açıklama
Anahtar Kelimeler
Onkoloji
Kaynak
Uluslararası Hematoloji-Onkoloji Dergisi
WoS Q Değeri
Scopus Q Değeri
Cilt
23
Sayı
4
