Düşük riskli mesane kanserinde nüksü öngörmede yeni bir belirteç: ELF-3 ve TSC-1 retrospektif incelenmesi
Küçük Resim Yok
Tarih
2022
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Namık Kemal Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Mesane kanseri oldukça heterojen ve multigenetik bir hastalıktır. Mesane kanserinde farklı evrelerdeki hastalarda farklı tedavi problemleriyle karşılaşılmaktadır. Düşük riskli invaziv olmayan mesane kanseri (İOMK) için de en önemli problemlerden biri nüks gelişimidir. Nüks gelişiminin non- invaziv tekniklerle önceden öngörülmesi bu hastaların daha yakından takip edilmesi ve bir sonraki tedavi basamağına daha erken geçilebilmesini sağlayacaktır. Bu amaçla düşük riskli İOMK'de nüks gelişimini öngörmek amacıyla CD44, CK5/6, CK20, GATA3, Cerb-B2, ELF3 ve TSC-1 immunohistokimyasal belirteçleri değerlendirildi. Çalışmamızda 2011 ile 2019 yılları arasında Namık Kemal Üniversitesi Tıp Fakültesi Hastanesi Üroloji Anabilim Dalı'nda TUR-M operasyonu yapılmış ve kliniğimizde takipli toplam 320 hastanın verileri retrospektif olarak tarandı. Çalışmaya dahil edilme kriterlerini karşılayan toplam 40 hasta çalışmaya dahil edildi. Bu 40 hastanın 20 tanesinin 3 yıllık takiplerinde nüks geliştiği gözlenirken, diğer 20 hastada ise 3 yıl boyunca herhangi bir nüks gelişmediği görüldü. Böylelikle çalışmaya dahil edilen 40 hasta nüks gelişme durumuna göre 2 gruba ayrılmış oldu. Bu 40 hastanın ilk TUR-M operasyonlarına ait parafine gömülü formalin ile fikse blokları Tekirdağ NKÜ Patoloji Laboratuvarı arşivinden alındı. Hastaların hepsinin patolojik tanıları aynı uzman üropatolog tarafından tekrar değerlendirildi. Blokların tamamına ürotelyal karsinomun büyüme paternlerinin tespit edilmesi için CK4 (Kreatin Kinaz 4), CK5/6, CK20, CD44(anti-CD44 SP37 tavşan monoklonal primer antikor), GATA3 (L50-823 fare monoklonal primer antikor),Cerb-B2 (insan epidermal büyüme faktörü resektörü 2), ELF-3 ve TSC-1 immunohistokimyasal belirteçler kullanılarak boyama gerçekleştirildi. Çalışmaya dahil edilen hastaların (%85) erkek, (%15) ise kadındı. Çalışmaya dahil edilen tüm hastaların ortalama yaşı 63,62 olarak tespit edildi. Çalışmaya dahil edilen hastaların meslekleri incelendiğinde ise nüks gelişen grupta 6 işçi, 1 memur, 1 ev hanımı ve 12 emekli mevcut iken nüks gelişmeyen grupta da 9 işçi, 2 memur, 1 ev hanımı ve 8 emekli mevcuttu. Nüks durumu ile yaş, cinsiyet, vki, meslek, sigara (paket/yıl), devam eden sigara kullanımı, tümör lokalizasyonu, en büyük tümör boyutu ve post-op erken epirubisin kullanımı arasında istatistiksel olarak anlamlı ilişki yoktur (p>0,05). Nüks durumu ile tümör sayısı sınıfları arasında istatistiksel olarak anlamlı ilişki tespit edilmiştir (p=0,036). Nüks olmayan 16 hastanın (%80,0) tümör sayısının 1 olduğu, nüks olan 9 hastanın (%45,0) tümör sayısının 2-4 olduğu belirlenmiştir. Tümör sayısı 1 olanların ağırlıklı olarak nüks olmadığı, tümör sayısı 2-4 ve ?5 olanların ise ağırlıklı olarak nüks olduğu belirlenmiştir. Bu bilgilere ek olarak, nüks olanlarda nükse kadar geçen süre ortalamasının 13,25 (ay) ve nüks olan bölgedeki tümör boyutunun 56 ortalama 0,57 cm olduğu belirlenmiştir. Nüks durumu ile CK5/6, GATA3, CerbB2, CK20 ve ELF3 parametreleri arasında istatistiksel olarak anlamlı ilişki yoktur (p>0,05). Nüks durumu ile CD44 durumu arasında istatistiksel olarak anlamlı ilişki tespit edilmiştir (p=0,022). Nüks olmayan 11 hastanın (%55,0) CD44 pozitif olduğu, nüks olan 16 hastanın (%80,0) CD44 negatif olduğu belirlenmiştir. CD44 pozitif olanların ağırlıklı olarak nüks olmadığı, CD44 negatif olanların ise ağırlıklı olarak nüks olduğu belirlenmiştir. Nüks durumu ile TSC1 durumu arasında istatistiksel olarak anlamlı ilişki tespit edilmiştir (p=0,003). Nüks olmayan 9 hastanın (%45,0) TSC1 negatif olduğu, nüks olan 19 hastanın (%95,0) TSC1 pozitif olduğu belirlenmiştir. TSC1 pozitif olanların ağırlıklı olarak nüks olduğu, TSC1 negatif olanların ise ağırlıklı olarak nüks olmadığı belirlenmiştir. Sonuçta, düşük riskli İOMK hastalarında değerlendirilen immunohistokimyasal belirteçlerden CK5/6, CK20, GATA3, CerbB2 ve ELF-3 nüksü öngörme açısından anlamsız bulunurken, CD44'ün düşük ekspresyonu ve TSC-1'in yüksek ekspresyonunun nüks gelişimini öngörebileceği sonucuna ulaşıldı. Bu belirteçler ile yapılan analiz ile nüks gelişimin öngörülerek bu hastalar daha yakından takip edilebilir ya da bir sonraki tedavi aşamalarına daha erken yönlendirilebilir.
Bladder cancer is a highly heterogeneous and multigenetic disease. Different treatment problems are encountered in patients with different stages of bladder cancer. One of the most important problems for low-risk non-invasive bladder cancer (IOMC) is the development of recurrence. Anticipating the development of recurrence using non-invasive techniques will enable these patients to be followed more closely and to switch to the next treatment step earlier. For this purpose, CD44, CK5/6, CK20, GATA3, Cerb-B2, ELF3 and TSC-1 immunohistochemical markers were evaluated to predict recurrence in low-risk IOMC. In our study, the data of 320 patients who underwent TUR-M operation in the Urology Department of Namık Kemal University Faculty of Medicine between 2011 and 2019 and were followed up in our clinic were retrospectively scanned. A total of 40 patients who met the inclusion criteria were included in the study. Recurrence was observed in 20 of these 40 patients during their 3-year follow-up, while no recurrence was observed in the other 20 patients for 3 years. Thus, 40 patients included in the study were divided into 2 groups according to their recurrence rate. Paraffin-embedded formalin and fixed blocks of these 40 patients' first TUR-M operations were obtained from the archive of Tekirdağ NKU Pathology Laboratory. Pathological diagnoses of all patients were re-evaluated by the same specialist uropathologist. CK4 (Creatine Kinase 4), CK5/6, CK20, CD44(anti-CD44 SP37 rabbit monoclonal primary antibody),GATA3 (L50-823 mouse monoclonal primary antibody),Cerb-B2 (human) for detection of growth patterns of urothelial carcinoma in all blocks Staining was performed using epidermal growth factor receptor 2), ELF-3 and TSC-1 immunohistochemical markers. The patients included in the study (85%) were male and (15%) female. The mean age of all patients included in the study was 63.62 years. When the occupations of the patients included in the study were examined, there were 6 workers, 1 civil servant, 1 housewife and 12 retirees in the relapsed group, while there were 9 workers, 2 civil servants, 1 housewife and 8 retirees in the non-relapsed group. There is no statistically significant relationship between recurrence status and age, gender, gender, occupation, smoking (pack/year), ongoing smoking, tumor localization, largest tumor size, and post-op early epirubicin use (p>0.05) . A statistically significant relationship was found between recurrence status and tumor number classes 58 (p=0.036). It was determined that the number of tumors in 16 patients (80.0%) without recurrence was 1, and the number of tumors in 9 patients with recurrence (45.0%) was 2-4. It was determined that those with a tumor number of 1 predominantly did not relapse, while those with a tumor number of 2-4 and ?5 were predominantly relapsed. In addition to this information, it was determined that the mean time to relapse was 13.25 (months) and the average tumor size in the relapsed region was 0.57 cm. There was no statistically significant relationship between relapse status and CK5/6, GATA3, CerbB2, CK20 and ELF3 parameters (p>0.05). A statistically significant correlation was found between relapse status and CD44 status (p=0.022). It was determined that 11 (55.0%) non-relapsed patients were CD44 positive, and 16 (80.0%) relapsed patients were CD44 negative. It was determined that those who were CD44 positive were predominantly non-relapsed, while those who were CD44 negative were predominantly relapsed. A statistically significant relationship was found between relapse status and TSC1 status (p=0.003). It was determined that 9 patients (45.0%) without relapse were TSC1 negative, and 19 patients with relapse (95.0%) were TSC1 positive. It was determined that TSC1 positive ones were predominantly relapsed, while TSC1 negative ones were predominantly non-relapsed. As a result, while immunohistochemical markers CK5/6, CK20, GATA3, CerbB2 and ELF-3 evaluated in low-risk IOMC patients were found to be insignificant in terms of predicting relapse, it was concluded that low expression of CD44 and high expression of TSC-1 could predict the development of relapse. By predicting the development of relapse with the analysis made with these markers, these patients can be followed more closely or referred to the next treatment stages earlier.
Bladder cancer is a highly heterogeneous and multigenetic disease. Different treatment problems are encountered in patients with different stages of bladder cancer. One of the most important problems for low-risk non-invasive bladder cancer (IOMC) is the development of recurrence. Anticipating the development of recurrence using non-invasive techniques will enable these patients to be followed more closely and to switch to the next treatment step earlier. For this purpose, CD44, CK5/6, CK20, GATA3, Cerb-B2, ELF3 and TSC-1 immunohistochemical markers were evaluated to predict recurrence in low-risk IOMC. In our study, the data of 320 patients who underwent TUR-M operation in the Urology Department of Namık Kemal University Faculty of Medicine between 2011 and 2019 and were followed up in our clinic were retrospectively scanned. A total of 40 patients who met the inclusion criteria were included in the study. Recurrence was observed in 20 of these 40 patients during their 3-year follow-up, while no recurrence was observed in the other 20 patients for 3 years. Thus, 40 patients included in the study were divided into 2 groups according to their recurrence rate. Paraffin-embedded formalin and fixed blocks of these 40 patients' first TUR-M operations were obtained from the archive of Tekirdağ NKU Pathology Laboratory. Pathological diagnoses of all patients were re-evaluated by the same specialist uropathologist. CK4 (Creatine Kinase 4), CK5/6, CK20, CD44(anti-CD44 SP37 rabbit monoclonal primary antibody),GATA3 (L50-823 mouse monoclonal primary antibody),Cerb-B2 (human) for detection of growth patterns of urothelial carcinoma in all blocks Staining was performed using epidermal growth factor receptor 2), ELF-3 and TSC-1 immunohistochemical markers. The patients included in the study (85%) were male and (15%) female. The mean age of all patients included in the study was 63.62 years. When the occupations of the patients included in the study were examined, there were 6 workers, 1 civil servant, 1 housewife and 12 retirees in the relapsed group, while there were 9 workers, 2 civil servants, 1 housewife and 8 retirees in the non-relapsed group. There is no statistically significant relationship between recurrence status and age, gender, gender, occupation, smoking (pack/year), ongoing smoking, tumor localization, largest tumor size, and post-op early epirubicin use (p>0.05) . A statistically significant relationship was found between recurrence status and tumor number classes 58 (p=0.036). It was determined that the number of tumors in 16 patients (80.0%) without recurrence was 1, and the number of tumors in 9 patients with recurrence (45.0%) was 2-4. It was determined that those with a tumor number of 1 predominantly did not relapse, while those with a tumor number of 2-4 and ?5 were predominantly relapsed. In addition to this information, it was determined that the mean time to relapse was 13.25 (months) and the average tumor size in the relapsed region was 0.57 cm. There was no statistically significant relationship between relapse status and CK5/6, GATA3, CerbB2, CK20 and ELF3 parameters (p>0.05). A statistically significant correlation was found between relapse status and CD44 status (p=0.022). It was determined that 11 (55.0%) non-relapsed patients were CD44 positive, and 16 (80.0%) relapsed patients were CD44 negative. It was determined that those who were CD44 positive were predominantly non-relapsed, while those who were CD44 negative were predominantly relapsed. A statistically significant relationship was found between relapse status and TSC1 status (p=0.003). It was determined that 9 patients (45.0%) without relapse were TSC1 negative, and 19 patients with relapse (95.0%) were TSC1 positive. It was determined that TSC1 positive ones were predominantly relapsed, while TSC1 negative ones were predominantly non-relapsed. As a result, while immunohistochemical markers CK5/6, CK20, GATA3, CerbB2 and ELF-3 evaluated in low-risk IOMC patients were found to be insignificant in terms of predicting relapse, it was concluded that low expression of CD44 and high expression of TSC-1 could predict the development of relapse. By predicting the development of relapse with the analysis made with these markers, these patients can be followed more closely or referred to the next treatment stages earlier.
Açıklama
Tıp Fakültesi, Üroloji Ana Bilim Dalı
Anahtar Kelimeler
Üroloji, Urology