Relationship between HLA class I antigen processing machinery component expression and the clinicopathologic characteristics of bladder carcinomas.
Relationship between HLA class I antigen processing machinery component expression and the clinicopathologic characteristics of bladder carcinomas.
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DOI：
10.1007/s00262-009-0765-9
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发表时间：
2010-03
期刊：
影响因子：
--
通讯作者：
Frierson HF Jr
中科院分区：
文献类型：
--
作者：
Cathro HP;Smolkin ME;Theodorescu D;Jo VY;Ferrone S;Frierson HF Jr
本研究的目的是分析膀胱癌(BC)中抗原处理机制(APM)成分的蛋白表达，并评价其表达缺陷的临床意义。来自167例原发膀胱癌的切除组织被用于创建组织微阵列。128个肿瘤为尿路上皮癌。用14株抗β-2微球蛋白、钙粘蛋白、钙网蛋白、Delta、Z、MB1、LMP2、LMP7、LMP10、HLAI类重链、TAP1、TAP2和ERP57的单抗和MHCI类相关抗原进行免疫组织化学染色。以6名受试者的正常尿路上皮切片作为对照。除MB1、LMP2和TAP2外，其余APM成分在UC中的表达均显著低于正常尿路上皮。不同年级UC患者APM各成分得分差异无统计学意义。鳞状细胞癌得分最高，UC居中，其他类型BC得分最低。高分期UC中Calnexin、LMP2、LMP7和LMP10的表达明显低于低分期UC。平均随访3.6年，UC的Delta评分较高(P=0.038)，而所有肿瘤类型的钙网蛋白评分较低(P=0.028)，生存率显著降低。大多数APM成分在UC中表达下调。与低期UC相比，高分期UC的免疫蛋白酶体成分得分较低。Delta和钙网蛋白的表达分别与UC和所有类型BC的生存有关。这些发现提示APM缺陷在BC的临床病程中起作用，在开发免疫治疗方法以控制其时应予以考虑。
The goal of this study was to analyze protein expression of antigen processing machinery (APM) components in bladder carcinoma (BC), and to assess the clinical significance of defects in their expression. Tissue from 167 cystectomies for primary BC was used to create a tissue microarray. 128 tumors were urothelial carcinoma (UC). Immunohistochemistry was performed using 14 monoclonal antibodies to APM components (β2-microglobulin, calnexin, calreticulin, delta, Z, MB1, LMP2, LMP7, LMP10, HLA class I heavy chain, tapasin, TAP1, TAP2 and ERp57) and MHC class I-related antigen (MICA). Sections of normal urothelium from six subjects were used as controls. All APM components except MB1, LMP2 and TAP2 had significantly lower staining in UC than in normal urothelium. No significant differences were found in APM component scores between different grades of UC. Squamous cell carcinoma had the highest scores, with UC intermediate and other types of BC lowest. High-stage UC demonstrated significantly lower staining for calnexin, LMP2, LMP7 and LMP10 than low-stage UC. With mean 3.6 years follow up, significantly worse survival was associated with a higher delta score in UC (P = 0.038) and a lower calreticulin score in all tumor types (P = 0.028). Most APM components were downregulated in UC. High-stage UC had lower scores for immunoproteasome components compared to low-stage UC. Delta and calreticulin protein expression was associated with survival in UC and in all types of BC, respectively. These findings suggest that APM defects play a role in the clinical course of BC and should be considered in developing immunotherapeutic approaches for its control.
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抗原加工机械和HLA I类缺陷与宫颈癌中临床病理结果的关联。
影响因子：
5.8
作者：
Mehta, Akash M.;Jordanova, Ekaterina S.;Kenter, Gemma G.;Ferrone, Soldano;Fleuren, Gert-Jan
通讯作者：
Fleuren, Gert-Jan
影响因子：
45.3
作者：
Madersbacher, S;Hochreiter, W;Studer, UE
通讯作者：
Studer, UE
影响因子：
11.5
作者：
Meissner, M;Reichert, TE;Seliger, B
通讯作者：
Seliger, B
影响因子：
6.6
作者：
Den Otter, W;Dobrowolski, Z;Zembala, M
通讯作者：
Zembala, M
影响因子：
6.4
作者：
Romero, JM;Jiménez, P;Ruiz-Cabello, F
通讯作者：
Ruiz-Cabello, F