中华实验眼科杂志
中華實驗眼科雜誌
중화실험안과잡지
CHINESE JOURNAL OF EXPERIMENTAL OPHTHALMOLOGY
2013年
6期
535-539
,共5页
范真%赵桂秋%赵超%高昂%王谦%徐强%林红%孙为荣
範真%趙桂鞦%趙超%高昂%王謙%徐彊%林紅%孫為榮
범진%조계추%조초%고앙%왕겸%서강%림홍%손위영
脉络膜肿瘤/黑色素瘤%M2丙酮酸激酶%蛋白激酶B%缺氧诱导因子-1
脈絡膜腫瘤/黑色素瘤%M2丙酮痠激酶%蛋白激酶B%缺氧誘導因子-1
맥락막종류/흑색소류%M2병동산격매%단백격매B%결양유도인자-1
Choroid neoplasms/melanoma%Pyruvate kinase M2%Akt%Hypoxia inducible factor-1
背景 研究发现肿瘤型M2丙酮酸激酶(M2-PK)已成为多种肿瘤组织的一种新型标志物,脉络膜黑色素瘤(CM)组织中M2-PK的表达及PI3 K/蛋白激酶B(Akt)通路、缺氧诱导因子-1(HIF-1)对CM生物学行为的影响有重要的临床意义. 目的 观察M2-PK在CM组织中的表达情况,研究M2-PK、Akt、HIF-1三者表达之间的关系,探讨其在CM发生发展中的作用及意义.方法 收集1992-2012年青岛大学医学院附属医院眼科病理室存档的CM标本30例和眼睑色素痣标本30例,采用免疫组织化学染色法检测M2-PK、Akt、HIF-1在两种组织中的表达情况,并结合临床及病理学资料对M2-PK、Akt、HIF-1与肿瘤细胞生物学行为的影响进行分析.采用x2检验对M2-PK、Akt、HIF-1在不同细胞类型的CM中、不同大小CM中及不同巩膜浸润情况CM组织中表达率的差异进行比较,并对M2-PK、Akt、HIF-1在CM与眼睑色素痣中表达率的差异进行比较；采用配对资料的关联性分析评估M2-PK、Akt、HIF-1在CM中表达的关联性. 结果 M2-PK、Akt在CM中表达的阳性率分别为73％ (22/30)和80％(24/30),在眼睑色素痣中的表达阳性率分别为40％ (12/30)和47％ (14/30),二者在CM中的表达阳性率均明显高于眼睑色素痣,差异均有统计学意义(x2=6.787,P=0.009;x2 =7.177,P=0.007)；HIF-1在CM中和在眼睑色素痣中的阳性表达率分别为70％ (21/30)和50％(15/30),差异无统计学意义(x2=2.500,P=0.114).M2-PK在梭形细胞型CM中的阳性表达率为57％(8/14),在类上皮细胞型CM中为87％ (7/8),在混合细胞型CM中为87％(7/8),总体差异无统计学意义(x2=3.617,P=0.172).M2-PK在小CM中的阳性表达率为44％ (4/9),中等CM为85％ (11/13),大CM为87％ (7/8),差异无统计学意义(x2=5.508,P=0.064).M2-PK在未浸润巩膜和浸润巩膜的CM中的阳性表达率分别为50％(7/14)、94％ (15/16),差异有统计学意义(x2=7.308,P=0.007).在CM中M2-PK与Akt、M2-PK与HIF-1、Akt与HIF-1的阳性表达均有关联(x2=12.315,P=0.000;x2 =17.175,P=0.000;x2=10.159,P=0.001),列联系数分别为0.539、0.603、0.503. 结论 M2-PK在CM细胞的增生、侵袭和转移过程中发挥重要作用,其表达和激活可能与PI3K/Akt-HIF-1通路有关.
揹景 研究髮現腫瘤型M2丙酮痠激酶(M2-PK)已成為多種腫瘤組織的一種新型標誌物,脈絡膜黑色素瘤(CM)組織中M2-PK的錶達及PI3 K/蛋白激酶B(Akt)通路、缺氧誘導因子-1(HIF-1)對CM生物學行為的影響有重要的臨床意義. 目的 觀察M2-PK在CM組織中的錶達情況,研究M2-PK、Akt、HIF-1三者錶達之間的關繫,探討其在CM髮生髮展中的作用及意義.方法 收集1992-2012年青島大學醫學院附屬醫院眼科病理室存檔的CM標本30例和眼瞼色素痣標本30例,採用免疫組織化學染色法檢測M2-PK、Akt、HIF-1在兩種組織中的錶達情況,併結閤臨床及病理學資料對M2-PK、Akt、HIF-1與腫瘤細胞生物學行為的影響進行分析.採用x2檢驗對M2-PK、Akt、HIF-1在不同細胞類型的CM中、不同大小CM中及不同鞏膜浸潤情況CM組織中錶達率的差異進行比較,併對M2-PK、Akt、HIF-1在CM與眼瞼色素痣中錶達率的差異進行比較；採用配對資料的關聯性分析評估M2-PK、Akt、HIF-1在CM中錶達的關聯性. 結果 M2-PK、Akt在CM中錶達的暘性率分彆為73％ (22/30)和80％(24/30),在眼瞼色素痣中的錶達暘性率分彆為40％ (12/30)和47％ (14/30),二者在CM中的錶達暘性率均明顯高于眼瞼色素痣,差異均有統計學意義(x2=6.787,P=0.009;x2 =7.177,P=0.007)；HIF-1在CM中和在眼瞼色素痣中的暘性錶達率分彆為70％ (21/30)和50％(15/30),差異無統計學意義(x2=2.500,P=0.114).M2-PK在梭形細胞型CM中的暘性錶達率為57％(8/14),在類上皮細胞型CM中為87％ (7/8),在混閤細胞型CM中為87％(7/8),總體差異無統計學意義(x2=3.617,P=0.172).M2-PK在小CM中的暘性錶達率為44％ (4/9),中等CM為85％ (11/13),大CM為87％ (7/8),差異無統計學意義(x2=5.508,P=0.064).M2-PK在未浸潤鞏膜和浸潤鞏膜的CM中的暘性錶達率分彆為50％(7/14)、94％ (15/16),差異有統計學意義(x2=7.308,P=0.007).在CM中M2-PK與Akt、M2-PK與HIF-1、Akt與HIF-1的暘性錶達均有關聯(x2=12.315,P=0.000;x2 =17.175,P=0.000;x2=10.159,P=0.001),列聯繫數分彆為0.539、0.603、0.503. 結論 M2-PK在CM細胞的增生、侵襲和轉移過程中髮揮重要作用,其錶達和激活可能與PI3K/Akt-HIF-1通路有關.
배경 연구발현종류형M2병동산격매(M2-PK)이성위다충종류조직적일충신형표지물,맥락막흑색소류(CM)조직중M2-PK적표체급PI3 K/단백격매B(Akt)통로、결양유도인자-1(HIF-1)대CM생물학행위적영향유중요적림상의의. 목적 관찰M2-PK재CM조직중적표체정황,연구M2-PK、Akt、HIF-1삼자표체지간적관계,탐토기재CM발생발전중적작용급의의.방법 수집1992-2012년청도대학의학원부속의원안과병리실존당적CM표본30례화안검색소지표본30례,채용면역조직화학염색법검측M2-PK、Akt、HIF-1재량충조직중적표체정황,병결합림상급병이학자료대M2-PK、Akt、HIF-1여종류세포생물학행위적영향진행분석.채용x2검험대M2-PK、Akt、HIF-1재불동세포류형적CM중、불동대소CM중급불동공막침윤정황CM조직중표체솔적차이진행비교,병대M2-PK、Akt、HIF-1재CM여안검색소지중표체솔적차이진행비교；채용배대자료적관련성분석평고M2-PK、Akt、HIF-1재CM중표체적관련성. 결과 M2-PK、Akt재CM중표체적양성솔분별위73％ (22/30)화80％(24/30),재안검색소지중적표체양성솔분별위40％ (12/30)화47％ (14/30),이자재CM중적표체양성솔균명현고우안검색소지,차이균유통계학의의(x2=6.787,P=0.009;x2 =7.177,P=0.007)；HIF-1재CM중화재안검색소지중적양성표체솔분별위70％ (21/30)화50％(15/30),차이무통계학의의(x2=2.500,P=0.114).M2-PK재사형세포형CM중적양성표체솔위57％(8/14),재류상피세포형CM중위87％ (7/8),재혼합세포형CM중위87％(7/8),총체차이무통계학의의(x2=3.617,P=0.172).M2-PK재소CM중적양성표체솔위44％ (4/9),중등CM위85％ (11/13),대CM위87％ (7/8),차이무통계학의의(x2=5.508,P=0.064).M2-PK재미침윤공막화침윤공막적CM중적양성표체솔분별위50％(7/14)、94％ (15/16),차이유통계학의의(x2=7.308,P=0.007).재CM중M2-PK여Akt、M2-PK여HIF-1、Akt여HIF-1적양성표체균유관련(x2=12.315,P=0.000;x2 =17.175,P=0.000;x2=10.159,P=0.001),렬련계수분별위0.539、0.603、0.503. 결론 M2-PK재CM세포적증생、침습화전이과정중발휘중요작용,기표체화격활가능여PI3K/Akt-HIF-1통로유관.
Background Researches showed that tumor pyruvate kinase M2 (M2-PK) is a novel marker of multiple tumors.Investigating the influence of M2-PK expression as well as hypoxia inducible factor-1 (HIF-1) and PI3K/Akt pathway on the biological behaviour of choroidal melanoma (CM) is of an important significance.Objective The purpose of this study was to investigate the expression of M2-PK,Akt and HIF-1 in CM and discuss their effects in the development of CM.Methods Thirty CM samples and 30 nevus samples were collected in Affiliated Hospital of Qingdao University Medical College.The percentages of M2-PK,Akt and HIF-1 expression in CM and nevus were detected by immunohistochemistry,and their association with clinicopathological parameters were statistically analyzed.The differences of the expressions of M2-PK,Akt and HIF-1 were evaluated by Chi-square test,and the correlations between M2-PK and Akt or HIF-1 were analyzed by correlation analysis of paired data.Results The percentages of positive expression of M2-PK and Akt in CM were 73％ (22/30) and 80％ (24/30),respectively,and those in nevus were 40％ (12/30) and 47％ (14/30) respectively,showing significant differences between the two types of tumors (x2 =6.787,P =0.009 ;x2 =7.177,P =0.007).An insignificant rate was found in HIF-1 expression in CM between the two types of tumors (70％ versus 50％,x2 =2.500,P =0.114).The positive expressing percentage of M2-PK was 57％ (8/14) in spindle cell type CM,87％ (7/8) in epithelioid cell type CM and 87％ (7/8) in mixed cell type CM,with significant difference among them (x2 =3.617,P=0.172).M2-PK was positively expressed in44％ (4/9) of small CM,85％ (11/13) of moderate CM and 87％ (7/8) of big CM,presenting a significant difference among them (x2 =5.508,P =0.064).An increasingly expressing percentage of M2-PK was seen in sclera invasive CM (94％) compared with sclera uninvasive CM (50％) (x2 =7.308,P=0.007).The correlations were seen in the expressing percentage between M2-PK and Akt (x2=12.315,P=0.000) as well as between M2-PK and HIF-1 (x2 =17.175,P=0.000) or between Akt and HIF-1 (x2=10.159,P=0.001).Conclusions The expression of M2-PK upregulates in CM,indicating that M2-PK plays an important role in the survival,development,invasion and metastasis of CM probably by PI3K/Akt-HIF-1 pathway.
