Küçük hücreli dışı akciğer karsinomlarında MUC4 ekspresyonu; E-cadherin hücre adezyon kompleksi; hücre proliferasyonu, apoptoz ve metastaz üzerine etkileri

Abstract

3. Yabana Dilde Özet - Summary ÜUC4 EXPRESSION IN NON-SRflÂLL CELL LUNG CANCER (NSCLC) AND IT'S EFFECTS ON E-CADHERIN CELL ADHESION COMPLEX, CELL PROLIFERATION, APOPTOSIS AND METASTASIS Zekiye Aydoğdu Dinç Lung carcinoma is the most common malignancy for both men and women and 60-65% of the lung carcinomas is NSCLC. Mucins.especially membrane-associated ones, have drown attraction in the recent years because of its probable effects on cancer pathogenesis and metastasis. Muc4, which is a membrane-associated mucin and which has ASPG-2 subunit has been reported to exist in non-tumoral and tumoral lung tissue. The effects of Muc4 in carsinogenesis and metastasis have been shown by in vitro and animal experiments. In this study; immunohistochemistry was used to detect Muc4, c-erbB2, PCNA and E-cadherin expression and apoptotic index for apoptosis on archival non- tumoral, tumoral and metastatic node tissues from 100 NSCLC lobectomy material. The results of all these parameters and between every parameter and tumor stage were analyzed by chi-square, Man Whitney U and Pearson tests. Muc4 is expressed in all non-tumoral bronchial epithelia and 85% of tumoral tissues. Muc4 expression increase significantly in tumoral tissue, compared to the non- tumoral bronchial tissue but no significant differences between histological types. There was significant correlation between increasing Muc4 and c-erbB2 expressions and between PCNA and Al. No significant difference has been found in PCNA counts between the cases with increased or not increased Muc4 expression, but Al was significantly decreased. These results point out that Muc4 increases with erbB2 and has a role in carsinogenesis. In our study, this role seems to be related with the increased apoptosis rather than cell proliferation.2. ÖZET KÜÇÜK HÜCRELİ DİŞİ AKCİĞER KARSİNO^LÂRINDÂ MUC4 EKSPRESYONU; E-CADHERÎN HÜCRE ADEZYON KOMPLEKSİ, HÜCRE PROLİFERASYOhSU, APOPTOZ VE METASTAZ ÜZERİNE ETKİLERİ Zekiye Aydoğdu Dinç Akciğer karsinomları kadın ve erkeklerde en sık görülen malignitelerdir. KHDAK'ları da akciğer karsinomlarının % 60-65'ini oluşturmaktadır. Müsinler, özellikle membrana bağlı müsin grupları, son yıllarda kanser patogenezi ve metastaz konusundaki olası etkileri yönünden ilgi çekmektedir. Membrana bağlı bir müsin olan, transmembran ASGP-2 altbirimi taşıyan, normal ve patolojik akciğer dokusunda bulunduğu bildirilen Muc4'ün in vitro ve hayvan deneyleri ile karsinogenez ve metastaz konusunda etkileri gösterilmiştir. Bu çalışmada 100 adet KHDAK olgusunda, ameliyat materyallerinden elde edilen tümörsüz bronş, tümör ve metastatik lenf nodu dokularında İHK tekniği ile Muc4, c-erbB2, PCNA, E-cadherin ekspresyonu ve apoptotik indeks araştırılmıştır. Tüm araştırılan parametrelerin kendi aralarındaki ilişki ve bu parametrelerin hepsinin tümör evresi ile ilişkisi %, Man Whitney U ve Pearson korelasyon testleri ile istatistiksel olarak araştırılmıştır. Muc4, tümörsüz bronş epitel hücrelerinde tüm olgularda ve tümörlü olguların %85'sinde ifade edilmektedir. Muc4 ekspresyonu, tümörsüz bronş dokusuna göre tümör dokusunda anlamlı artış göstermektedir. Tümörlü dokuda Muc4 ifadesinde histolojik tiplere göre farklılık saptanmamıştır. Tümör dokularında, artmış Muc4 ve c-erbB2 ifadeleri arasında ve PCNA ile Al arasında anlamlı korelasyon mevcuttur. Muc4 artışı olan ve olmayan olgular arasında PCNA değeri yüksek olgu sayısı bakımından anlamlı fark saptanmamıştır. Al değerlerinde ise anlamlı azalma mevcuttur. Sonuçlar, Muc4'ün erbB2 ile birlikte arttığını ve karsinogenezde rolü olduğunu düşündürmektedir. Bu rol bizim çalışmamızda, proliferasyon artışına bağlı olmayıp apoptoz ile ilişkili gibi görünmektedir.

3. Yabana Dilde Özet - Summary ÜUC4 EXPRESSION IN NON-SRflÂLL CELL LUNG CANCER (NSCLC) AND IT'S EFFECTS ON E-CADHERIN CELL ADHESION COMPLEX, CELL PROLIFERATION, APOPTOSIS AND METASTASIS Zekiye Aydoğdu Dinç Lung carcinoma is the most common malignancy for both men and women and 60-65% of the lung carcinomas is NSCLC. Mucins.especially membrane-associated ones, have drown attraction in the recent years because of its probable effects on cancer pathogenesis and metastasis. Muc4, which is a membrane-associated mucin and which has ASPG-2 subunit has been reported to exist in non-tumoral and tumoral lung tissue. The effects of Muc4 in carsinogenesis and metastasis have been shown by in vitro and animal experiments. In this study; immunohistochemistry was used to detect Muc4, c-erbB2, PCNA and E-cadherin expression and apoptotic index for apoptosis on archival non- tumoral, tumoral and metastatic node tissues from 100 NSCLC lobectomy material. The results of all these parameters and between every parameter and tumor stage were analyzed by chi-square, Man Whitney U and Pearson tests. Muc4 is expressed in all non-tumoral bronchial epithelia and 85% of tumoral tissues. Muc4 expression increase significantly in tumoral tissue, compared to the non- tumoral bronchial tissue but no significant differences between histological types. There was significant correlation between increasing Muc4 and c-erbB2 expressions and between PCNA and Al. No significant difference has been found in PCNA counts between the cases with increased or not increased Muc4 expression, but Al was significantly decreased. These results point out that Muc4 increases with erbB2 and has a role in carsinogenesis. In our study, this role seems to be related with the increased apoptosis rather than cell proliferation.A significant correlation has been found between E-cadherin and Muc4 expression although no significant difference between Muc4(+) E-cadherin(-) with Muc4(-) E-cadherin(+) and Muc4(+) E-cadherin(+) cases interms of tumor size and stage. Number of metastasis was found to be significantly increased in cases which have both increased Muc4 and E-cadherin expression. This result points out that Muc4 builds its anti-adhesive effect by blocking E-cadherin. Muc4 and c-erbB2 expressions, PCNA counts and Al do not differ significantly between tumor and metastatic nodes except E-cadherin which. No significant relationship has been found between Muc4 expression and advanced stage. Muc4, which stains epithelial cells, is commonly visible on endothelial cell surface. Keywords: NSCLC, PCNA, muc4, c-erbB2, e-cadherin, apoptosis * This study was supported by Dokuz Eylul University Research Foundation (Project No: 03.KB.SA?.010)