Bcl-2、Bax和GST-π在非霍奇金淋巴瘤中的表达研究
摘要
目的：研究Bcl-2、Bax和GST-π在非霍奇金淋巴瘤(NHL)中的表达及其对化疗效果的影响。方法：收集59例非霍奇金淋巴瘤患者的临床资料及淋巴结活检组织蜡块。采用免疫组化S-P法检测蜡块标本中Bcl-2、Bax和GST-π的表达，应用相应的统计学方法分析各项检测指标与临床病理分型之间的相互关系，以及与临床化疗疗效之间的关系。结果：1）Bcl-2在B细胞性NHL中的表达强度和表达率均高于T细胞性NHL(P < 0.01)。2）在B和T细胞性NHL之间Bax和GST-π的表达无显著性差异(P>.05)。3）Bcl-2在低度恶性NHL中的表达要显著高于中高度恶性NHL( P < 0.05)。4）Bax在低度恶性NHL和中高度恶性NHL中的表达无显著性差异( P > 0.05)。5）在中高度恶性NHL组，GST-π表达显著高于低度恶性组( P < 0.05)。6）Bcl-2表达阳性的中高度恶性NHL其完全缓解率要显著低于Bcl-2阴性表达组。7）GST-π表达阳性的中高度恶性NHL患者，其完全缓解率显著低于GST-π阴性表达组。8）Bcl-2、GST-π双阳性患者其治疗完全缓解率显著低于Bcl-2、GST-π双阴性患者(P <0.01)。结论：Bcl-2在B淋巴细胞性NHL中高表达，GST-π则在中高度恶性NHL中高表达，Bax在不同的细胞类型和恶性程度NHL间表达无差异；Bcl-2和GST-π表达组化疗CR率低，以Bcl-2和GST-π双阳性组CR率最低，提示二者可以作为化疗疗效不佳的指标。
Objective: To study the expression and sign ifcance of Bcl-2、Bax and GST-πin non-Hodgk inps lymphom a (NHL ). Methods: Fifty night cases of NHL were examined with immunohistochemist ry technique. Results: 1) The expression of Bcl-2 in B-cell lymphoma was significantly higher than that in T-cell lymphoma(P<0.01). 2) Obvious difference of Bax and GST-πexpression in B-cell lymphoma and T-cell lymphoma was not observed (P>0.05) . 3) The expression of Bcl-2 in low malignancy group was significantly higher than that in intermediate and high malignancy group (P<0.01). 4) There was not significant difference of Bax expression in low malignancy group and intermediate and high malignancy group (P<0.01). 5)The expression of GST-π in intermediate and high malignancy group was significantly higher than that in low malignancy group (P<0.01). 6)Complete Remission rate in cases without Bcl-2 expression was higher than that with Bcl-2 expression in intermediate and high malignancy group. 7)Complete Remission rate in cases with GST-πexpression was lower than that without GST-πexpression in intermediate and high malignancy group. 8) Complete Remission rate in cases with GST-πand Bcl-2 expression was lower than that without GST-π and Bcl-2 expression in intermediate and high malignancy group Conclusions: Poor chemotherapy response was seen in cases with Bcl-2 and GST-πexpression in intermediate and high malignancy group NHL, Bcl-2 and GST-πwere able to be used as predictor of prognosis.
Objective: To study the expression and sign ifcance of Bcl-2、Bax and GST-πin non-Hodgk inps lymphom a (NHL ). Methods: Fifty night cases of NHL were examined with immunohistochemist ry technique. Results: 1) The expression of Bcl-2 in B-cell lymphoma was significantly higher than that in T-cell lymphoma(P<0.01). 2) Obvious difference of Bax and GST-πexpression in B-cell lymphoma and T-cell lymphoma was not observed (P>0.05) . 3) The expression of Bcl-2 in low malignancy group was significantly higher than that in intermediate and high malignancy group (P<0.01). 4) There was not significant difference of Bax expression in low malignancy group and intermediate and high malignancy group (P<0.01). 5)The expression of GST-π in intermediate and high malignancy group was significantly higher than that in low malignancy group (P<0.01). 6)Complete Remission rate in cases without Bcl-2 expression was higher than that with Bcl-2 expression in intermediate and high malignancy group. 7)Complete Remission rate in cases with GST-πexpression was lower than that without GST-πexpression in intermediate and high malignancy group. 8) Complete Remission rate in cases with GST-πand Bcl-2 expression was lower than that without GST-π and Bcl-2 expression in intermediate and high malignancy group Conclusions: Poor chemotherapy response was seen in cases with Bcl-2 and GST-πexpression in intermediate and high malignancy group NHL, Bcl-2 and GST-πwere able to be used as predictor of prognosis.
引文
第四届全国淋巴瘤学术座谈会技术组. 1985 年成都会议修订非何杰金氏淋巴瘤工作分类方案及诊断指标[J]. 肿瘤, 1985, 5(6):277-9
2.于 镔,石群立,孙桂勤.原发性中枢神经系统恶性淋巴瘤Bcl-2蛋白的表达.诊断病理学杂志, 1997，4(3):145
3. 常新忠，史朝晖，王占民，等. GST-π及TOPO在胰腺癌中的表达及临床意义.2002，42（3）：43-44
4.孙燕. 抗肿瘤新药的临床试用方法. 中华肿瘤杂志,1980 ,2 (2) :150～154.
5. Miller AB ,Hoogstraten B ,Staquet M,et al . Reporting results of cancer treatment . Cancer ,1981 ,47(2) :207～210.
6 Nomura M,Watari J ,Yokota K,et al.Morphogenesis of nonpolypoid colorectal adenomas and early arcinomas assessed by cell proliferation and apoptosis. Virchows Arch ，2000 ;437(1) :17
7 Mullauer L ,Gruber P ,Sebinger D ,et al. Mutations in apoptosis genes: a pathogenetic factor for human disease. Mutat Res ，2001 ;488(3) :211
8 Tsujimoto Y,Cossman J,Jaffe E,et al.Involvement of the bcl-2 gene in human follicular lymphoma [J].Science ,1985,228(4706):1440-1443.
9 McDonnell TJ ,Korsmeyer SJ.Progression from lymphoid hyperplasia to high-grade malignant lymphoma in mice transgenic for the t(14;18) [J] . Nature,1991,349 (6306) : 254-256.
10 Sorenson CM,Rogers SA,Korsmeyer SJ,et al.Fulminant metanephric apoptosis and abnormal kidney development in bcl-2-deficient mice [J].AmJ Physiol,1995,268(1 Pt2):F73-F81.
11 Oltvai ZN,Milliman CL,Korsmeyer SJ.Bcl-2 heterodimerizes in vivo with a conserved homolog,Bax, that accelerates programmed cell death [J] . Cell , 1993 , 74(4):609-619.
12 Knudson CM,Tung KS,Tourtellotte WG,et al.Bax2deficient mice with lymphoid hyperplasia and male germ cell death [J] . Science,1995,270(5233):96-99.
13 Oltvai ZN ,mlilliman CL ,Korsmeyer SJ ,et al.Bcl22 heterodimerizes
in vivo with a conserved homolog Bax ,that accelerates programmed cell death. Cell 1993;74(4):6541
14 张小田,陈维刚,黎健. p53基因诱导膀胱癌细胞HTB9凋亡及相关基因的表达. 肿瘤 2001;21(1):29
15 Alsabeh R,Wilson CS,Ahn CW,et al.Expression of bcl-2 by breast cancer : A possible diagnostic application [J].Mod Pathol,1996,9(4):439-444.
16 Leahy DT,Mulcahy HE, O′Donoghue DP,et al.Bcl-2 protein expression is associated with better prognosis in colorectal cancer[J] . Histopathology , 1999 , 35(4):360-367.
17 Sarbia M,Bittinger F, Grabellus F,et al. Expression of Bax, apro-apoptotic member of the Bcl-2 family,in esophageal squamous cell carcinoma[J] . Int J Cancer , 1997,73(4):508-513.
18 Marx D,Binder C, Meden H,et al. Differential expression of apoptosis associated genes bax and bcl-2 in ovarian cancer [J] .Anticancer Res,1997,17(3C): 2233-2240.
19 Pezzella F, Tse GC, Cordell JL，et al. Expression of the Bcl-2 oncogene protein is not specific for the 14: 18 chromomal translocation. A m J P athol, 1990; 137: 225
20 Lippo ren P, Aaltomma S. Apoptosis in bladder cancer as related to standard p rogno stic factors, prognosis. J Pathol, 1994; 173:333
21 Szakas G, Jakab K, Antal F , et al . Diagnostics of multidrug resistance in cancer[J] . Pathol Oncol Res , 1998 , 4(4): 2512-2571
22 Konishi I , Nanbu K, Mandai M, et al . Tumor response to neoadjuvant chemotherapy correlates with the expression of P-glycoprotein and PCNA but not GST2πin the tumor cells of cervical carcinoma [J] . Gynecol Oncol ,1998 ,70(3) :365-371
23 Goldstein LJ , Galski H , Fojo A , et al . Expression of a multidrug resistance gene in human cancers [J] .J Natl Cancer Inst ,1989 ,81(2):116-124
24 Terrier P , Townsend AJ ,Coindre JM, et al . An immunohistochemical
study of pi class glutathione S2 transferase expression in normal human tissue. AmJ Pathol,1990 , 137:845-853
25 Linn SC,Honkoop AH , Hoekman K,et al.p53 and P-glycoprotein are often co-expressed and are associated with poor prognosis in breast cancer [J].BrJ Cancer,1996,74(1):63-68
26 Van der Aee AG, Hollema H , Surmeijer AJ , et al1 Value of P-glycoprotein , glutathione S2transferase π, c2erbB22 , and p53 as prognostic factors in ovarian carcinoma [J].J Clin Oncol ,1995 ,13:70-78
27 Takeuchi A,Kaneko S,Matsushita E,et al.Interferon-alpha modulates resistance to cisplatin in three human hepatoma cell lines. J Gastroenterol , 1999 ,34 :351-358.
28 Zhang K,Yang EB,Wong KP,et al.GSH,GSH-related enzymes and GS-X pump in relation to sensitivity of human tumor cell lines to chlorambucil and adriamycin.Int J Oncol,1999,14:861-867
29.Schecter RL ,Alaoui MA ,Woo A ,et al. Cancer Res ,1993 ;53 :4900～4906
30.Cheng AL , Su IJ ,Chen YC , et al . Expression of P-glycoprotein and glutathione-S-transferase in recurrent lymphomas : the possible role of Epstein-Barr virus ,immunophenotypes ,and other predisposing factors. J Clin Oncol , 1993 ,11 (1) :109～15.
31.李春海, 郭亚军主编. 肿瘤分子生物学研究进展[M].北京:军事医学科学出版社, 1996.103-104
32 CHUNG H C , RHA S Y, KIM J H , et al. P – gly-coprotein : the intermediate end point of drug response to induction chemotherapy in locally advanced breast cancer [J] . Breast Cancer Res Treat , 1997 , 42 : 65
33 戴广海,石廷章,李春海.肺癌MDR1和GST-πmRNA 水平测定及临床意义[J].中国肿瘤临床,1999,22(3):6
34 付保进,张云汉,王尧河,等.食管癌发生发展过程GST-π基因表达研究[J].中华肿瘤杂志,1999,21(1):29
2.于 镔,石群立,孙桂勤.原发性中枢神经系统恶性淋巴瘤Bcl-2蛋白的表达.诊断病理学杂志, 1997，4(3):145
3. 常新忠，史朝晖，王占民，等. GST-π及TOPO在胰腺癌中的表达及临床意义.2002，42（3）：43-44
4.孙燕. 抗肿瘤新药的临床试用方法. 中华肿瘤杂志,1980 ,2 (2) :150～154.
5. Miller AB ,Hoogstraten B ,Staquet M,et al . Reporting results of cancer treatment . Cancer ,1981 ,47(2) :207～210.
6 Nomura M,Watari J ,Yokota K,et al.Morphogenesis of nonpolypoid colorectal adenomas and early arcinomas assessed by cell proliferation and apoptosis. Virchows Arch ，2000 ;437(1) :17
7 Mullauer L ,Gruber P ,Sebinger D ,et al. Mutations in apoptosis genes: a pathogenetic factor for human disease. Mutat Res ，2001 ;488(3) :211
8 Tsujimoto Y,Cossman J,Jaffe E,et al.Involvement of the bcl-2 gene in human follicular lymphoma [J].Science ,1985,228(4706):1440-1443.
9 McDonnell TJ ,Korsmeyer SJ.Progression from lymphoid hyperplasia to high-grade malignant lymphoma in mice transgenic for the t(14;18) [J] . Nature,1991,349 (6306) : 254-256.
10 Sorenson CM,Rogers SA,Korsmeyer SJ,et al.Fulminant metanephric apoptosis and abnormal kidney development in bcl-2-deficient mice [J].AmJ Physiol,1995,268(1 Pt2):F73-F81.
11 Oltvai ZN,Milliman CL,Korsmeyer SJ.Bcl-2 heterodimerizes in vivo with a conserved homolog,Bax, that accelerates programmed cell death [J] . Cell , 1993 , 74(4):609-619.
12 Knudson CM,Tung KS,Tourtellotte WG,et al.Bax2deficient mice with lymphoid hyperplasia and male germ cell death [J] . Science,1995,270(5233):96-99.
13 Oltvai ZN ,mlilliman CL ,Korsmeyer SJ ,et al.Bcl22 heterodimerizes
in vivo with a conserved homolog Bax ,that accelerates programmed cell death. Cell 1993;74(4):6541
14 张小田,陈维刚,黎健. p53基因诱导膀胱癌细胞HTB9凋亡及相关基因的表达. 肿瘤 2001;21(1):29
15 Alsabeh R,Wilson CS,Ahn CW,et al.Expression of bcl-2 by breast cancer : A possible diagnostic application [J].Mod Pathol,1996,9(4):439-444.
16 Leahy DT,Mulcahy HE, O′Donoghue DP,et al.Bcl-2 protein expression is associated with better prognosis in colorectal cancer[J] . Histopathology , 1999 , 35(4):360-367.
17 Sarbia M,Bittinger F, Grabellus F,et al. Expression of Bax, apro-apoptotic member of the Bcl-2 family,in esophageal squamous cell carcinoma[J] . Int J Cancer , 1997,73(4):508-513.
18 Marx D,Binder C, Meden H,et al. Differential expression of apoptosis associated genes bax and bcl-2 in ovarian cancer [J] .Anticancer Res,1997,17(3C): 2233-2240.
19 Pezzella F, Tse GC, Cordell JL，et al. Expression of the Bcl-2 oncogene protein is not specific for the 14: 18 chromomal translocation. A m J P athol, 1990; 137: 225
20 Lippo ren P, Aaltomma S. Apoptosis in bladder cancer as related to standard p rogno stic factors, prognosis. J Pathol, 1994; 173:333
21 Szakas G, Jakab K, Antal F , et al . Diagnostics of multidrug resistance in cancer[J] . Pathol Oncol Res , 1998 , 4(4): 2512-2571
22 Konishi I , Nanbu K, Mandai M, et al . Tumor response to neoadjuvant chemotherapy correlates with the expression of P-glycoprotein and PCNA but not GST2πin the tumor cells of cervical carcinoma [J] . Gynecol Oncol ,1998 ,70(3) :365-371
23 Goldstein LJ , Galski H , Fojo A , et al . Expression of a multidrug resistance gene in human cancers [J] .J Natl Cancer Inst ,1989 ,81(2):116-124
24 Terrier P , Townsend AJ ,Coindre JM, et al . An immunohistochemical
study of pi class glutathione S2 transferase expression in normal human tissue. AmJ Pathol,1990 , 137:845-853
25 Linn SC,Honkoop AH , Hoekman K,et al.p53 and P-glycoprotein are often co-expressed and are associated with poor prognosis in breast cancer [J].BrJ Cancer,1996,74(1):63-68
26 Van der Aee AG, Hollema H , Surmeijer AJ , et al1 Value of P-glycoprotein , glutathione S2transferase π, c2erbB22 , and p53 as prognostic factors in ovarian carcinoma [J].J Clin Oncol ,1995 ,13:70-78
27 Takeuchi A,Kaneko S,Matsushita E,et al.Interferon-alpha modulates resistance to cisplatin in three human hepatoma cell lines. J Gastroenterol , 1999 ,34 :351-358.
28 Zhang K,Yang EB,Wong KP,et al.GSH,GSH-related enzymes and GS-X pump in relation to sensitivity of human tumor cell lines to chlorambucil and adriamycin.Int J Oncol,1999,14:861-867
29.Schecter RL ,Alaoui MA ,Woo A ,et al. Cancer Res ,1993 ;53 :4900～4906
30.Cheng AL , Su IJ ,Chen YC , et al . Expression of P-glycoprotein and glutathione-S-transferase in recurrent lymphomas : the possible role of Epstein-Barr virus ,immunophenotypes ,and other predisposing factors. J Clin Oncol , 1993 ,11 (1) :109～15.
31.李春海, 郭亚军主编. 肿瘤分子生物学研究进展[M].北京:军事医学科学出版社, 1996.103-104
32 CHUNG H C , RHA S Y, KIM J H , et al. P – gly-coprotein : the intermediate end point of drug response to induction chemotherapy in locally advanced breast cancer [J] . Breast Cancer Res Treat , 1997 , 42 : 65
33 戴广海,石廷章,李春海.肺癌MDR1和GST-πmRNA 水平测定及临床意义[J].中国肿瘤临床,1999,22(3):6
34 付保进,张云汉,王尧河,等.食管癌发生发展过程GST-π基因表达研究[J].中华肿瘤杂志,1999,21(1):29
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