Mesanenin noninvaziv ve invaziv ürotelyal karsinomlarında B7-H3, tim-3, BTLA'nın immunhistokimyasal analizi, grade ve lenf nodu tutulumu ile ilişkisinin belirlenmesi
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Tarih
2019
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Yayıncı
Necmettin Erbakan Üniversitesi Meram Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Mesane ürotelyal karsinomu en sık görülen 9. kanser tipidir. Yüzeyel mesane karsinomlarında 5 yıllık sağkalım %90'ın üzerindeyken kasa invaze mesane karsinomlarında bu oranın %45 ile %55 arasında bildirilmiştir. Bu durum immün kontrol noktalarını bloke eden antikorlar gibi yeni tedavi yöntemlerini araştırmaya yönlendirmiştir. İmmun kontrol noktaları bağışıklık tepkisinin tipini, büyüklüğünü, süresini düzenlemekle görevli hem uyarıcı hem de inhibe edici yollardan oluşur. BTLA, TİM-3 ve B7-H3 immun kontrol noktalarından olup T hücre ilişkili inhibitör reseptörlerdir. Çalışmamızda mesane ürotelyal karsinomlarında tümör hücrelerinde B7-H3, TIM-3 ve BTLA reseptörlerinin ekspresyon durumları ile bunların prognostik faktörlerle ilişkisini irdelemeyi ve neticede gelecekte bu moleküller üzerinden etki edecek ilaçların mesanenin ürotelyal karsinomlarında kullanımı ile ilgili ipucu elde edebilmeyi amaçladık. Çalışmamıza Meram Tp Fakültesi Patoloji Anabilim Dalında 2013-2018 yıllarında noninvaziv veya invaziv ürotelyal karsinom tanılı 90 adet vaka dahil edildi. 13 adet normal görünümlü mesane dokusu kontrol grubu olarak belirlendi. Tüm olgulara immünohistokimyasal yöntem ile BTLA, TİM-3 ve B7-H3 çalışıldı. İmmunhistokimyasal çalışmanın sonuçları prognostik faktörlerden yaş, cinsiyet, histolojik derece, invazyon derinliği, lenf nodu metastazı varlığı ile ilişkileri istatistiksel olarak karşılaştırıldı. 90 adet ürotelyal karsinom olgusunun 60 tanesinde (%67,4) BTLA ekspresyonu tespit edilirken, 11 tanesinde (%12,2) yüksek ekspresyonu mevcuttu. BTLA ekspresyonu ile yaş, cinsiyet, histolojik grade, invazyon derinliği ve lenf nodu metastazı varlığı arasında istatiksel olarak anlamlı fark saptanmadı. TİM-3 ekpresyonu ile ileri Tevre arasında anlamlı ilişki mevcutken (p=0,001) histolojik derece ve lenf nodu metastazı varlığı ile arasında istatiksel olarak anlamlı korelasyon saptanmadı. B7-H3 ekspresyonu ile histolojik grade ve ileri Tevre arasında anlamlı korelasyon saptanırken lenf nodu metastazı varlığı ile arasında anlamlı fark tespit edilmedi. 17 olguda primer tümör dokusunda ve metastatik lenf nodu dokusunda BTLA, TİM-3 ve B7-H3 ekpsresyonları arasında anlamlı fark saptanmadı. Çalışmamız literatürde mesanenin ürotelyal karsinomlarında tümör hücrelerinde BTLA ekspresyonunu immunhistokimyasal yöntemle gösteren ve B7-H3 ekspresyonu ile yüksek histolojik derece ve ileri Tevre korelasyonunu gösteren ilk araştırmadır.
Urothelial carcinoma of the bladder is the 9th most prevalent type of cancer. Superficial bladder carcinomas are associated with a 90% five-year survival rate, however, this rate was reported to vary between 45% and 55% in cases of muscle invasive bladder carcinoma. This has promoted research on novel treatment methods such as antibodies that block the immune checkpoints. Immune checkpoints consist of stimulatory and inhibitory pathways that are tasked with regulating the type, strength, and duration of the immune response. The immune checkpoints BTLA, TIM-3, and B7-H3 are T-cell co-inhibitory receptors. This study aims to investigate the expression levels of B7-H3, TIM-3, and BTLA receptors in tumor cells and their relationship with prognostic factors in urothelial carcinoma of the bladder, and consequently, obtain clues about the future use of medications that would take effect through these molecules in the treatment of urothelial carcinomas. This study included 90 cases who were diagnosed with noninvasive or invasive urothelial carcinomas between 2013-2018 in the Pathology Department of Meram Faculty of Medicine. The control group was comprised of 13 bladder tissues with a normal appearance. All cases were tested for BTLA, TIM-3, B7-H3 using immunohistochemistry. The results of the immunohistochemical work-up was statistically compared to prognostic factors including age, sex, histological grade, depth of invasion, and the presence of lymph node metastasis. BTLA expression was detected in 60 (67.4%) of the 90 urothelial carcinoma cases and 11 of these (12.2%) showed high expression. BTLA expression was not statistically correlated with age, sex, histological grade, the depth of invasion, and the presence of lymph node metastasis. TIM-3 expression was significantly correlated with an advanced T-stage (p=0.001), however, it did not have a statistically significant correlation with histological grade and the presence of lymph node metastasis. B7-H3 expression was significantly correlated with histological grade and an advanced T-stage (p=0.001), however, it did not have a statistically significant correlation with the presence of lymph node metastasis. In 17 cases, levels of BTLA, TIM-3, and B7-H3 expression were not significantly different between the primary tumor tissue and the metastatic lymph node tissue. Our study is the first to demonstrate BTLA expression in tumor cells in urothelial carcinoma of the bladder using immunohistochemistry and show a correlation between B7-H3 expression and a high histological grade and T-stage.
Urothelial carcinoma of the bladder is the 9th most prevalent type of cancer. Superficial bladder carcinomas are associated with a 90% five-year survival rate, however, this rate was reported to vary between 45% and 55% in cases of muscle invasive bladder carcinoma. This has promoted research on novel treatment methods such as antibodies that block the immune checkpoints. Immune checkpoints consist of stimulatory and inhibitory pathways that are tasked with regulating the type, strength, and duration of the immune response. The immune checkpoints BTLA, TIM-3, and B7-H3 are T-cell co-inhibitory receptors. This study aims to investigate the expression levels of B7-H3, TIM-3, and BTLA receptors in tumor cells and their relationship with prognostic factors in urothelial carcinoma of the bladder, and consequently, obtain clues about the future use of medications that would take effect through these molecules in the treatment of urothelial carcinomas. This study included 90 cases who were diagnosed with noninvasive or invasive urothelial carcinomas between 2013-2018 in the Pathology Department of Meram Faculty of Medicine. The control group was comprised of 13 bladder tissues with a normal appearance. All cases were tested for BTLA, TIM-3, B7-H3 using immunohistochemistry. The results of the immunohistochemical work-up was statistically compared to prognostic factors including age, sex, histological grade, depth of invasion, and the presence of lymph node metastasis. BTLA expression was detected in 60 (67.4%) of the 90 urothelial carcinoma cases and 11 of these (12.2%) showed high expression. BTLA expression was not statistically correlated with age, sex, histological grade, the depth of invasion, and the presence of lymph node metastasis. TIM-3 expression was significantly correlated with an advanced T-stage (p=0.001), however, it did not have a statistically significant correlation with histological grade and the presence of lymph node metastasis. B7-H3 expression was significantly correlated with histological grade and an advanced T-stage (p=0.001), however, it did not have a statistically significant correlation with the presence of lymph node metastasis. In 17 cases, levels of BTLA, TIM-3, and B7-H3 expression were not significantly different between the primary tumor tissue and the metastatic lymph node tissue. Our study is the first to demonstrate BTLA expression in tumor cells in urothelial carcinoma of the bladder using immunohistochemistry and show a correlation between B7-H3 expression and a high histological grade and T-stage.
Açıklama
Anahtar Kelimeler
Mesane, noninvaziv, ürotelyal, karsinom
Kaynak
WoS Q Değeri
Scopus Q Değeri
Cilt
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Künye
Türk, N. (2019). Mesanenin noninvaziv ve invaziv ürotelyal karsinomlarında B7-H3, tim-3, BTLA'nın immunhistokimyasal analizi, grade ve lenf nodu tutulumu ile ilişkisinin belirlenmesi. (Yayınlanmamış tıpta uzmanlık tezi) Necmettin Erbakan Üniversitesi, Meram Tıp Fakültesi Cerrahi Tıp Bilimleri Tıbbi Patoloji Anabilim Dalı, Konya.
