中华病理学杂志
中華病理學雜誌
중화병이학잡지
Chinese Journal of Pathology
2009年
1期
35-41
,共7页
于宝华%周晓燕%肖秀英%颜士岩%秦涛%施达仁
于寶華%週曉燕%肖秀英%顏士巖%秦濤%施達仁
우보화%주효연%초수영%안사암%진도%시체인
淋巴瘤,大细胞,弥漫型%1-磷脂酰肌醇3-激酶%蛋白激酶类%逆转录聚合酶链反应
淋巴瘤,大細胞,瀰漫型%1-燐脂酰肌醇3-激酶%蛋白激酶類%逆轉錄聚閤酶鏈反應
림파류,대세포,미만형%1-린지선기순3-격매%단백격매류%역전록취합매련반응
Lymphoma,large-cell,diffuse%1-phosphatidylinositol 3-kinase%Protein kinases%Reverse transcriptase polymerase chain reaction
目的 研究AKT/mTOR通路在弥漫性大B细胞淋巴瘤(DLBCL)中的活化及其与bcl-6基因表达等指标的相关性,并探讨其在不同类型DLBCL中的作用.方法 用免疫组织化学方法 检测100例DLBCL及10例淋巴结反应性增生新鲜组织中pAKT、pmTOR的表达;运用TaqMan即时荧光逆转录聚合酶链反应(real-time RT-PCR)技术检测上述DLBCL中bcl-6 mRNA含量;同时用免疫组织化学方法 观察其中75例相应石蜡组织中bcl-6、CD10和MUM1的表达并据此进行分型.结果 (1)pAKT和pmTOR在DLBCL中的阳性率分别为76.0%(76/100)和75.0%(75/100),二者的表达强度、阳性细胞分布一致.(2)bcl-6蛋白与mRNA表达水平显著相关.pAKT和pmTOR高表达组的bel-6蛋白阳性率与mRNA水平均低于pAKT和pmTOR低表达或不表达者(均P<0.01).(3)非生发中心B细胞样(non-GCB)型DLBCL中pAKT和pmTOR的阳性率分别为82.5%(47/57)和84.2%(48/57),高于GCB型中的阳性比8/18和8/18(均P<0.01).(4)pAKT和pmTOR在男性患者中的表达略高于女性患者,pAKT和pmTOR阳性患者中乳酸脱氢酶(LDH)异常者略高于阴性患者中的比例,但差异均没有统计学意义(P>0.05).pAKT和pmTOR的表达与年龄、临床分期、卡氏体力状况评分(KPS)、B症状之间没有相关性(P>0.05).结论 AKT/mTOR信号转导通路活化在DLBCL发生中起重要作用,特别与bel-6低表达或不表达以及non-GCB亚型密切相关,并有望成为部分DLBCL治疗的新靶点.
目的 研究AKT/mTOR通路在瀰漫性大B細胞淋巴瘤(DLBCL)中的活化及其與bcl-6基因錶達等指標的相關性,併探討其在不同類型DLBCL中的作用.方法 用免疫組織化學方法 檢測100例DLBCL及10例淋巴結反應性增生新鮮組織中pAKT、pmTOR的錶達;運用TaqMan即時熒光逆轉錄聚閤酶鏈反應(real-time RT-PCR)技術檢測上述DLBCL中bcl-6 mRNA含量;同時用免疫組織化學方法 觀察其中75例相應石蠟組織中bcl-6、CD10和MUM1的錶達併據此進行分型.結果 (1)pAKT和pmTOR在DLBCL中的暘性率分彆為76.0%(76/100)和75.0%(75/100),二者的錶達彊度、暘性細胞分佈一緻.(2)bcl-6蛋白與mRNA錶達水平顯著相關.pAKT和pmTOR高錶達組的bel-6蛋白暘性率與mRNA水平均低于pAKT和pmTOR低錶達或不錶達者(均P<0.01).(3)非生髮中心B細胞樣(non-GCB)型DLBCL中pAKT和pmTOR的暘性率分彆為82.5%(47/57)和84.2%(48/57),高于GCB型中的暘性比8/18和8/18(均P<0.01).(4)pAKT和pmTOR在男性患者中的錶達略高于女性患者,pAKT和pmTOR暘性患者中乳痠脫氫酶(LDH)異常者略高于陰性患者中的比例,但差異均沒有統計學意義(P>0.05).pAKT和pmTOR的錶達與年齡、臨床分期、卡氏體力狀況評分(KPS)、B癥狀之間沒有相關性(P>0.05).結論 AKT/mTOR信號轉導通路活化在DLBCL髮生中起重要作用,特彆與bel-6低錶達或不錶達以及non-GCB亞型密切相關,併有望成為部分DLBCL治療的新靶點.
목적 연구AKT/mTOR통로재미만성대B세포림파류(DLBCL)중적활화급기여bcl-6기인표체등지표적상관성,병탐토기재불동류형DLBCL중적작용.방법 용면역조직화학방법 검측100례DLBCL급10례림파결반응성증생신선조직중pAKT、pmTOR적표체;운용TaqMan즉시형광역전록취합매련반응(real-time RT-PCR)기술검측상술DLBCL중bcl-6 mRNA함량;동시용면역조직화학방법 관찰기중75례상응석사조직중bcl-6、CD10화MUM1적표체병거차진행분형.결과 (1)pAKT화pmTOR재DLBCL중적양성솔분별위76.0%(76/100)화75.0%(75/100),이자적표체강도、양성세포분포일치.(2)bcl-6단백여mRNA표체수평현저상관.pAKT화pmTOR고표체조적bel-6단백양성솔여mRNA수평균저우pAKT화pmTOR저표체혹불표체자(균P<0.01).(3)비생발중심B세포양(non-GCB)형DLBCL중pAKT화pmTOR적양성솔분별위82.5%(47/57)화84.2%(48/57),고우GCB형중적양성비8/18화8/18(균P<0.01).(4)pAKT화pmTOR재남성환자중적표체략고우녀성환자,pAKT화pmTOR양성환자중유산탈경매(LDH)이상자략고우음성환자중적비례,단차이균몰유통계학의의(P>0.05).pAKT화pmTOR적표체여년령、림상분기、잡씨체력상황평분(KPS)、B증상지간몰유상관성(P>0.05).결론 AKT/mTOR신호전도통로활화재DLBCL발생중기중요작용,특별여bel-6저표체혹불표체이급non-GCB아형밀절상관,병유망성위부분DLBCL치료적신파점.
Objective (1) To investigate the activation of AKT/mTOR signaling transducfion pathway in DLBCL and its association with the expression of bcl-6 and some other clinical pathologic factors. (2) To estimation of the signaling pathway function in diverse subtypes of DLBCL and its potential value in the targeted treatment of DLBCL. Methods hnmunohistochemical (IHC) EnVision staining was used to detect the expressions of pAKT and pmTOR in 100 DLBCL and 10 reactive hyperplasia fresh lymph node samples; TaqMan real-time reverse transcription polymerase chain reaction (real-time RT-PCR) technique was used to explore the expression of bcl-6 mRNA in the DLBCL samples. IHC staining was used to detect the expressions of bcl-6, CD10 and MUM1 in 75 of the 100 corresponding paraffln-embedded samples and these 75 DLBCL samples were subdivided into GCB and non-GCB subgroups. Results (1) The expression of pAKT and pmTOR was 76% (76/100) and 75% (75/100), respectively, and the expression of the two proteins correlated with each other. (2) The expression of bcl-6 protein and mRNA significantly correlated with each other. The expression of bcl-6 protein and mRNA in pAKT and pmTOR high-expression group was significantly lower than that in low-expression group (both P<0.01 ). (3) The expression of pAKT and pmTOR in non-GCB group was 82.5% (47/57) and 84.2% (48/57), respectively, which were significantly higher than that in GCB group, which showed an expression rate of 44.4% (8/18) and 44.4% (8/18), respectively (both P<0.01). (4) The expression of pAKT and pmTOR in male was higher than that in female, and the percentage of patients with abnormal LDH in pAKT and pmTOR positive groups was higher than that in negative groups, although there were no statistical significance ( both P>0.05). There was no relationship between the expression of pAKT and pmTOR and age, sex, stage, KPS and B symptoms (P> 0.05). Conclusions Activation of AKT/mTOR signaling pathway plays an important role in the development of DLBCL, and it is closely related to the low or non-expression of bcl-6 and non-GCB subgroup. Molecules in this pathway might serve as the new targets in the treatment of certain group of DLBCL.
