Skp2、p27、PTEN在眼附属器B细胞非霍奇金淋巴瘤中的表达和意义

摘要

目的 探讨眼附属器B细胞非霍奇金淋巴瘤中S期激酶相关蛋白2(Skp2)、p27和PTEN蛋白的表达及其相关性.方法 实验研究.收集1995年1月至2011年12月青岛大学附属医院眼科手术切除的眼附属器B细胞非霍奇金淋巴瘤病理标本30例；以同期眼部反应性淋巴组织增生标本(n=10)作为对照组.采用免疫组织化学法分别检测眼附属器B细胞非霍奇金淋巴瘤标本和对照组标本中Skp2、p27和PTEN的表达情况,以病理分级作为眼附属器B细胞非霍奇金淋巴瘤的独立因素进行分析.各组间Skp2、p27及PTEN表达情况的比较采用x2检验,3种蛋白相互关系的分析采用Spearman等级相关分析.结果 Skp2、p27、PTEN的阳性表达率与年龄、性别、发病部位无关(P＞0.05),而与肿瘤的病理类型有关(P＜0.05).与对照组(Skp2:0/10；p27:10/10；PTEN:10/10)相比,眼附属器B细胞非霍奇金淋巴瘤中Skp2的表达率(76.7％,23/30)显著增高(x2=19.79,P=0.001),而p27(73.3％,22/30)和PTEN (56.7％,17/30)的表达率显著降低(x2 =8.37,P=0.039;x2=13.48,P=0.004).随着眼附属器B细胞非霍奇金淋巴瘤病理分级的提高,Skp2的表达率显著增高,p27和PTEN的表达显著降低.其中在黏膜相关淋巴组织结外边缘区B细胞淋巴瘤中,Skp2的表达分别与p27、PTEN呈负相关(r=-0.134,P＜0.05;r=-0.883,P＜0.05),p27与PTEN呈正相关(r=0.828,P＜0.05).结论 p27和PTEN蛋白表达的缺失及Skp2的表达水平升高可能与眼附属器B细胞非霍奇金淋巴瘤的发生有关,并可根据3种蛋白的表达区分肿瘤的不同类型；其中在黏膜相关淋巴组织结外边缘区B细胞非霍奇金淋巴瘤中,3种蛋白存在相关性.%Objective To investigate the expression and the correlation of protein of S-phase kinase associationprotien 2 (Skp2),p27 and phosphatases phosphatase and tensin homologue (PTEN) in non-Hodgkin B-cell lymphoma (NHL) of ocular adnexa.Methods Experimental study.Paraffin sections were collected from patients suffering from B cell NHL (n =30) in Qingdao Affiliated Hospital from January 1995to January 2011 and lymphadenosis (n =10) of ocular adnexa as the control group.The expression of Skp2,p27 and PTEN proteins were detected by immunohistochemistry and the positive expression rate between lymphomas and lymphadenosis was compared by x2 inspection.Spearman rank correlation was used to estimate the relationships among three proteins in ocular lymphoma.Pathologic grade were evaluated as independent factor of clinical information.Results The expression of three proteins were related to pathologic type of tumors,but not related to age,gender,pathogenetic locations.In non-Hodgkin B-cell lymphoma of ocular adnexa,the expression of Skp2 (76.7％,23/30) was higher than that in control group (0/10) (x2 =19.79,P =0.001),while the expression of p27(73.3％,22/30) and PTEN(56.7％,17/30)was lower than that in the control group(10/10 and 10/10) (x2 =8.37,P =0.039 ; x2 =13.48,P =0.004).With the increase of pathologic grade,Skp2 labeling frequency increase gradually,while p27 and PTEN labeling frequency decrease gradually; there was a negative correlation between p27 and Skp2 in MALT (r =-0.134,P ＜0.05) while there was a positive correlation between p27 and PTEN(r =0.828,P ＜ 0.05).The relationgship between Skp2 and PTEN was also negative (r =-0.883,P ＜ 0.05).Conclusions The higher expression of Skp2 and lower expression of p27 and PTEN may play a role in the tumorigenesis and different pathologic type of the B cell NHL of ocular adnexa.The expressions of three proteins correlate with each other in mucosa-associated lymphoid tissue.