Publication: Yüzeyel mesane tümörü progresyonunda epidermal büyüme faktörü (EGF) ve EGF reseptörü (EGFR) ekspresyonunun tümör prognozu ile ilintisi
Abstract
Ürotelyumdan kaynağını alan mesanenin değişken epitel hücreli karsinomu (DEHK), çok değişik biyolojik tavırlar sergileyebilmektedir. Bu biyolojik davranış çeşitliliğini öngörebilecek klinik bir bulgu mevcut değildir. Bu çalışmada, 35 hastaya ait mesane tümörü örneklerinde immunhistokimyasal yöntemle EGF ve EGFR ekspresyonu çalışılmış ve sonuçlar tümörün biyolojik davranışı ile ilişkilendirebilmek amacıyla histopatolojik ve klinik bulgular ile karşılaştırılmıştır. Bir avidin-biyotin yöntemi olan LAB-SA tekniği ile gerçekleştirilen immunhistokimyasal çalışmada primer antikor olarak EGF ekspresyonu için rekombinan insan EGF'sine karşı geliştirilmiş bir tavşan poliklonal antikoru, EGFR ekspresyonu için ise bir fare monoklonal antikoru, kromojen olarak ise DAB kullanılmıştır. Endoskopik transüretral rezeksiyon (TUR) cerrahi yöntemi ile elde edilen mesane tümörü spesimenlerinin Hematoksilen ve Eozin boyası ile histopatolojik değerlendirmesi sonucunda %80 olguda yüzeyel olarak tanımlanan mukoza ve lamina propriada sınırlı, %20'sinde ise lamina muskularise invaziv mesane tümörü saptandı. Tüm çalışma grubunda tümör evresi arttıkça ve diferansiyasyon derecesinde kötüleşme izlendi. EGF ekspresyonu invaziv tümörlerde yüzeyel tümörlere oranla istatistiksel anlamlı olarak yüksek bulundu. EGFR ekspresyonu da invaziv tümörlerde yüzeyel tümörlere oranla daha yoğun izlenmesine rağmen aradaki fark ististiksel olarak anlamlı bulunmadı. EGF ekspresyonu, tümör evresinden bağımsız olarak iyi diferansiye tümörlerde orta derecede diferansiye tümörlere oranla anlamlı olarak düşük bulundu. EGFR ekspresyonunda, artan diferansiyasyon derecesi ile birlikte oransal bir artış izlendiyse de aradaki fark istatistiksel olarak anlamlı bulunmadı. Aynı şekilde, EGF ve EGFR ekspresyonu da genel olarak tümör nüksü ya da ilerlemesi saptanan olgularda oransal olarak daha yoğun izlendiyse de aradaki fark istatistiksel anlama ulaşamamıştır. Sonuç olarak, insan mesane ürotelyal karsinomunda EGF ve EGFR ekspresyonu tümörün biyolojik davranışı ile ilişkili bulunmuştur. Bu alanda, daha çok hasta sayısıyla yapılacak immunhistokimyasal çalışmalara gereksinim vardır. THE ROLE OF EGF AND EGFR EXPRESSION IN THE PROGRESSION OF SUPERFICIAL BLADDER TUMORS
Transitional cell carcinoma of the bladder (TCCA) originates from urothelium and may present a diverse biological behavior that may be difficult to predict. In this study, EGF and EGFR expressions were studied by immunohistochemistry on bladder tumor specimens and results were correlated with histopathological findings and clinical parameters that constitute the biological behavior of the tumor. Immunohistochemical studies were conducted an avidin-biotin technique (LAB-SA). Primary antibody for EGF was a rabbit polyclonal antibody raised against recombinant human EGF and for EGFR was a mouse monoclonal antibody. DAB was used as the chromogen. Histopathological evaluation was performed on Hematoxylin & Eozin stained bladder tumor slides that revealed a superficial TCCA (limited to urothelium and lamina propria) in 80%, and an invasive TCCA (with invasion of lamina muscularis) in 20%. A marked relation was found between tumor stage and tumor differentiation. EGF expression was found to be significantly increased in invasive TCCA compared with superficial tumors. Although EGFR expression was also found to be increased in invasive TCCA compared to superficial, the difference was not quite statistically significant. In well-differentiated TCCA, EGF expression was found to be significantly less than in moderately differentiated tumors. EGFR expression revealed a proportional increase in parallel to differentiation grade which however was not statistically quite significant. Likewise, EGF and EGFR expression was found to be increased in recurrent and progressive TCCA but the difference was again insignificant. As a conclusion, this study has shown that EGF and EGFR expression correlates to a certain extent with the biological behavior and histopathological findings in TCCA of the bladder. The study further indicates the need for future immunohistochemical studies in this field with larger number of patients.
Transitional cell carcinoma of the bladder (TCCA) originates from urothelium and may present a diverse biological behavior that may be difficult to predict. In this study, EGF and EGFR expressions were studied by immunohistochemistry on bladder tumor specimens and results were correlated with histopathological findings and clinical parameters that constitute the biological behavior of the tumor. Immunohistochemical studies were conducted an avidin-biotin technique (LAB-SA). Primary antibody for EGF was a rabbit polyclonal antibody raised against recombinant human EGF and for EGFR was a mouse monoclonal antibody. DAB was used as the chromogen. Histopathological evaluation was performed on Hematoxylin & Eozin stained bladder tumor slides that revealed a superficial TCCA (limited to urothelium and lamina propria) in 80%, and an invasive TCCA (with invasion of lamina muscularis) in 20%. A marked relation was found between tumor stage and tumor differentiation. EGF expression was found to be significantly increased in invasive TCCA compared with superficial tumors. Although EGFR expression was also found to be increased in invasive TCCA compared to superficial, the difference was not quite statistically significant. In well-differentiated TCCA, EGF expression was found to be significantly less than in moderately differentiated tumors. EGFR expression revealed a proportional increase in parallel to differentiation grade which however was not statistically quite significant. Likewise, EGF and EGFR expression was found to be increased in recurrent and progressive TCCA but the difference was again insignificant. As a conclusion, this study has shown that EGF and EGFR expression correlates to a certain extent with the biological behavior and histopathological findings in TCCA of the bladder. The study further indicates the need for future immunohistochemical studies in this field with larger number of patients.