Publication: Neoadjuvan kemoterapi alan lokal ileri evre meme kanseri hastalarında dolaşımdaki tümör hücresi moleküler analizleri
No Thumbnail Available
Date
2017-10-26
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Amaç: İzole edilen dolaşımdaki tümör hücrelerinin (CTC)
analizi bir "sıvı biyopsi" olarak kanser tedavisinin ve
prognozunun öngörülebilmesini sağlayan invaziv
olmayan bir kişiye özel tıp uygulamasıdır. Bu çalışmanın
amacı neoadjuvan kemoterapi alan lokal ileri evre meme
kanserli hastalardan tedavi öncesi ve sonrası periferal
kan örnekleri alınarak, CTC moleküler
karakterizasyonunu yapmak ve tedaviye verilen yanıt ile
ilişkisini ortaya koymaktır.
Gereç-Yöntem: Çalışmaya 36 neoadjuvan kemoterapi
alan lokal ileri evre meme kanserli hasta dahil edilmiş ve
hastalardan tedavi öncesi ve sonrası 10 ml kan örnekleri
alınmıştır. CTC izolasyonu, tanımlanması ve moleküler
analizlerinde immuno-magnetik temelli AdnaTest kitleri
kullanılmış, meme kanseri (GA733-2, Muc-1 ve Her-2,
Aktin), EMT (PI3Kα, Akt-2, TWIST1) ve kök hücre (ALDH1)
markerları incelenmiştir. Görüntüleme Agilent 2100
Bioanalyzer cihazı kulllanılarak DNA 1000 LabChip ile
gerçekleştirilmiştir. CTC pozitifliği ve çalışılan markerlar
ile tedaviye yanıt (patolojik tam cevap (PCR) ve rezidual
hastalık) açısından anlamlılık, Fisher’s Exact test ile analiz
edilmiştir.
Bulgular: Otuzaltı hastanın 6'sında (%16,7) tedavi
öncesinde CTC pozitifliği saptanmıştır. CTC pozitif olan 6
hastanın 4'ünde kök hücre markeri olan ALDH1 pozitifliği
gözlenmiştir (p=0,0245) (Tablo 1). EMT markerlarından
PI3Kα ise 3 hastada pozitif bulunmuştur. Hasta takipleri
ve tedaviye verilen cevaplar izlenmeye devam
etmektedir.
Sonuç: Neoadjuvan kemoterapi alan lokal ileri evre
meme kanseri hastalarında CTC pozitifliği ve kök hücre
markerlarının analizi tedaviye verilecek olan cevabın ve
hasta sağkalım oranlarının ön görülebilmesi için önemli
bir yöntem olabilir. Çalışmalarımız bu kapsamda devam
etmektedir.
Objective: Analysis of circulating tumor cells (CTC) as a "liquid biopsy" is a non-invasive personalized medicine application that allows prediction of cancer treatment and prognosis. The purpose of this study is to determine the molecular characterization of CTCs and to reveal the relation with the response given to the therapy by taking peripheral blood samples before and after treatment from patients taking neoadjuvant chemotherapy. Materials-Methods: Locally advanced breast cancer stage patients who will receive neoadjuvant chemotherapy were included in the study and 10 ml blood samples were taken before and after treatment. Immuno-magnetic bead based AdnaTest kits were used for CTC isolation, identification and molecular analysis. Breast cancer (GA733-2, Muc-1 and Her-2), EMT (PI3Kα, Akt-2, TWIST1) and stem cell (ALDH1) markers were examined. Imaging was performed with DNA 1000 LabChip using Agilent 2100 Bioanalyzer instrument. CTC positivity and response to treatment with studied markers (pathologic complete response and residual disease) were analyzed using Fisher's Exact test. Results: CTC positivity was detected before treatment in 6 of 36 (16.7%) patients. Four of the six CTC positive patients had ALDH1 positivity as a stem cell marker (p = 0.0245). PI3Ka, one of the EMT markers, was found positive in 3 patients. Patient follow-up and response to treatment are still being monitored. Conclusion: CTC positivity and analysis of stem cell markers in locally advanced breast cancer stage patients who received neoadjuvant chemotherapy may be an important method for predicting the response and patient survival rates. Our work continues in this context.
Objective: Analysis of circulating tumor cells (CTC) as a "liquid biopsy" is a non-invasive personalized medicine application that allows prediction of cancer treatment and prognosis. The purpose of this study is to determine the molecular characterization of CTCs and to reveal the relation with the response given to the therapy by taking peripheral blood samples before and after treatment from patients taking neoadjuvant chemotherapy. Materials-Methods: Locally advanced breast cancer stage patients who will receive neoadjuvant chemotherapy were included in the study and 10 ml blood samples were taken before and after treatment. Immuno-magnetic bead based AdnaTest kits were used for CTC isolation, identification and molecular analysis. Breast cancer (GA733-2, Muc-1 and Her-2), EMT (PI3Kα, Akt-2, TWIST1) and stem cell (ALDH1) markers were examined. Imaging was performed with DNA 1000 LabChip using Agilent 2100 Bioanalyzer instrument. CTC positivity and response to treatment with studied markers (pathologic complete response and residual disease) were analyzed using Fisher's Exact test. Results: CTC positivity was detected before treatment in 6 of 36 (16.7%) patients. Four of the six CTC positive patients had ALDH1 positivity as a stem cell marker (p = 0.0245). PI3Ka, one of the EMT markers, was found positive in 3 patients. Patient follow-up and response to treatment are still being monitored. Conclusion: CTC positivity and analysis of stem cell markers in locally advanced breast cancer stage patients who received neoadjuvant chemotherapy may be an important method for predicting the response and patient survival rates. Our work continues in this context.
Description
Keywords
Citation
AKKİPRİK M., YUMUK P. F., UĞURLU M. Ü., KOCA S., ERZİK C., ALAN Ö., PEKER EYÜBOĞLU İ., GÜLLÜ AMURAN G., ÖZER S. A., \"Neoadjuvan kemoterapi alan lokal ileri evre meme kanseri hastalarında dolaşımdaki tümör hücresi moleküler analizleri\", Tıbbi Biyoloji ve Genetik kongresi, 26 - 29 Ekim 2017