Expression of UDP-N-acetyl-α-D-galactosamine-polypeptide N-acetylgalactosaminyltransferase isozyme 3 in the subserosal layer correlates with postsurgical survival of pathological tumor stage 2 carcinoma of the gallbladder
Expression of UDP-N-acetyl-α-D-galactosamine-polypeptide N-acetylgalactosaminyltransferase isozyme 3 in the subserosal layer correlates with postsurgical survival of pathological tumor stage 2 carcinoma of the gallbladder
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DOI：
10.1158/1078-0432.ccr-1024-03
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发表时间：
2004-03-15
影响因子：
11.5
通讯作者：
Irimura, T
中科院分区：
文献类型：
--
作者：
Miyahara, N;Shoda, J;Irimura, T
目的与实验设计：目前对病理肿瘤2期（pT(2)）胆囊癌发生发展的分子机制知之甚少。o -糖基化位点的改变可能通过调节靶粘蛋白的生物学特性与癌细胞的恶性行为有关。udp - n-乙酰- α - d-半乳糖胺-多肽n-乙酰-半乳糖胺基转移酶同工酶3 （GalNAc-T3）具有上皮腺特异性表达并催化粘蛋白型o糖基化。本研究通过免疫组化检测34例pT2胆囊癌GalNAc-T3的表达水平，探讨GalNAc-T3表达水平与复发方式及术后生存的关系。结果：胆囊癌组织中GalNAc-T3蛋白和mRNA的表达水平明显高于邻近非癌组织和完整胆囊组织。GalNAc-T3的免疫染色在癌上皮中被识别，亚细胞定位分为颗粒型和弥漫性。34例pT2癌中，50%的GalNAc-T3在浆膜下最深处浸润部位为颗粒型，50%的GalNAc-T3为弥漫性。GalNAc-T3浸润最深部位弥漫性定位的术后复发率（65%）明显高于颗粒性定位的术后复发率（23%,P < 0.05）。结论：在pT2胆囊癌中，浆膜下层GalNAc-T3的弥漫性定位与疾病的侵袭性相关。这种表型可能是与恶性行为相关的独特生物学特征。
Purpose and Experimental Design: Little is known about the molecular events leading to the development and progression of pathological tumor stage 2 (pT(2)) gallbladder carcinoma. An alteration in the site of O-glycosylation may be associated with malignant behavior of carcinoma cells by modulation of the biological properties of the target mucin. The UDP-N-acetyl-alpha-D-galactosamine-polypeptide N-acetylgalactosaminyltransferase isozyme 3 (GalNAc-T3) has the epithelial gland-specific expression and catalyzes mucin-type O-glycosylation. In this study, immunohistochemistry was performed to determine the expression level of GalNAc-T3 in 34 cases of pT2 gallbladder carcinoma to determine the correlation of the GalNAc-T3 expression level with mode of recurrence and postsurgical survival.Results: The expression levels of GalNAc-T3 protein and mRNA were increased in gallbladder carcinomas compared with the levels in adjacent noncancerous tissues and in intact gallbladders. Immunostaining of GalNAc-T3 was recognized in the cancerous epithelia, and the subcellular localization was classified into granular and diffuse types. In the 34 cases of pT2 carcinoma, the localization of GalNAc-T3 was granular type in 50% and diffuse type in 50% of the cases at the deepest invading sites in the subserosal layer. Postsurgical recurrence was significantly more frequent in cases showing diffuse-type localization of GalNAc-T3 at the deepest invading sites (65%) than in those showing granular-type localization (23%; P < 0.05). Postsurgical survival was significantly poorer in cases showing diffusetype localization than in those showing granular-type localization (P = 0.033)Conclusions: In pT2 gallbladder carcinoma, the presence of diffuse-type localization of GalNAc-T3 in the subserosal layer is correlated with aggressiveness of the disease. This phenotype may serve as a unique biological feature associated with the malignant behavior.