ER、PR、Cerb-B2、P53蛋白、LRP、GST-π、TopoⅡ在乳腺粘液癌中的表达
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摘要
目的:观察ER、PR、Cerb-B2、肺耐药蛋白(LRP)、谷胱甘肽-硫-转移酶π(GST-π)、拓扑异构酶Ⅱ(TopoⅡ)和肿瘤抑癌基因产物P53蛋白在乳腺粘液癌组织中的表达并探讨其临床意义。
方法:应用免疫组织化学LDP方法对42例乳腺粘液癌标本ER、PR、Cerb-B2、LRP、GST-π、TopoⅡ和P53蛋白表达进行检测,并结合临床病理资料进行统计分析。
结果:42例乳腺粘液癌,有腋窝淋巴结转移的10例病人中混合性粘液癌为7例,单纯性粘液癌3例,两者之间存在相关性(p=0.027,r=0.367);ER阳性表达率80.9%,PR阳性表达率85.7%,CerbB-2阳性表达率47.6%,p53阳性表达率45.2%,LRP阳性表达率85.7%,GST-π的阳性表达率为64.3%,ToPoⅡ的阳性表达率为52.4%;ER表达和组织类型有关(p=0.038、r=0.369),与P53的表达相关(P=0.04,r=0.319);P53的表达与GST-π阳性表达存在相关(p=0.003.r=0.478),LRP、ToPoⅡ的表达与p53表达不相关;LRP表达与GST-π表达间存在相关性(p=0.008,r=0.406);ToPoⅡ在不同肿瘤大小组间存在差异,p=0.032;ER、PR、Cerb-B2、TopoⅡ、LRP、GST-π、P53蛋白在乳腺粘液癌中的表达与患者的年龄、月经状态、腋窝淋巴结转移不相关,P＞0.05。
结论:联合检测TopoⅡ、LRP、GST-π、P53蛋白在乳腺粘液癌中的表达,并分析与激素受体状况、临床病理因素之间的关系,有助于评估乳腺粘液癌的的生物学行为,对其化疗和内分泌治疗方案的制定有重要的参考价值。
Objective:Observe the expressions of ER,PR,Cerb-B2,lung resistanceprotein(LRP), glutathione-S-transferase(GST-π),topoisomeraseⅡ(TopoⅡ),tumor suppressor gene product P53 protein in breast mucinous carcinoma and its clinical significance.
Methods:Immunohistochemistry(LDP) method was used to detect the expressions of ER,PR,Cerb-B2,P53,LRP,GST-π,TopoⅡin 42 cases of mucinous carcinoma of the breast,Statistical analyses were used to study the relationship between the test results and different clinicopathological parameters.
Results:42 cases of mucinous breast cancer,there are 10 cases of lymph node metastasis in patients with mixed mucinous carcinoma of 7 cases,3 cases of pure mucinous carcinoma,The axillary's metastasis node numbers was related to the different histological types,p=0.027,r=0.367;The expressions of ER、PR、Cerb-B2、P53、LRP、GST-π、TopoⅡin this group were 80.9%,85.7%,47.6%,45.2%,85.7%, 64.3%,52.4%respectively;the ER was distinctly related to the different histological types and the expressions of P53,(p＜0.05);the expressions of P53 was related to the expressions of GST-π(p=0.003.r=0.478);LRP was related to GST-π(p=0.008.r=0.406);No relationship was found between P53 and LRP、TopoⅡ; The expressions of TopoⅡwas related the tumor diameter(p=0.03).And no relationship was found between ER、PR、Cerb-B2、TopoⅡ、LRP、GST-π、P53 protein in mucinous carcinoma of the breast and patient's age,menstrual status,axillary lymph node metastasis.
Conclusion:Combined detection of TopoⅡ,LRP,GST-π,P53 protein in mucinous breast carcinoma and analysis of hormone receptor status and clinicopathological factors can help assess the biological behavior of the mucinous breast carcinoma and have important reference value to the chemotherapy and endocrine therapy.
方法:应用免疫组织化学LDP方法对42例乳腺粘液癌标本ER、PR、Cerb-B2、LRP、GST-π、TopoⅡ和P53蛋白表达进行检测,并结合临床病理资料进行统计分析。
结果:42例乳腺粘液癌,有腋窝淋巴结转移的10例病人中混合性粘液癌为7例,单纯性粘液癌3例,两者之间存在相关性(p=0.027,r=0.367);ER阳性表达率80.9%,PR阳性表达率85.7%,CerbB-2阳性表达率47.6%,p53阳性表达率45.2%,LRP阳性表达率85.7%,GST-π的阳性表达率为64.3%,ToPoⅡ的阳性表达率为52.4%;ER表达和组织类型有关(p=0.038、r=0.369),与P53的表达相关(P=0.04,r=0.319);P53的表达与GST-π阳性表达存在相关(p=0.003.r=0.478),LRP、ToPoⅡ的表达与p53表达不相关;LRP表达与GST-π表达间存在相关性(p=0.008,r=0.406);ToPoⅡ在不同肿瘤大小组间存在差异,p=0.032;ER、PR、Cerb-B2、TopoⅡ、LRP、GST-π、P53蛋白在乳腺粘液癌中的表达与患者的年龄、月经状态、腋窝淋巴结转移不相关,P＞0.05。
结论:联合检测TopoⅡ、LRP、GST-π、P53蛋白在乳腺粘液癌中的表达,并分析与激素受体状况、临床病理因素之间的关系,有助于评估乳腺粘液癌的的生物学行为,对其化疗和内分泌治疗方案的制定有重要的参考价值。
Objective:Observe the expressions of ER,PR,Cerb-B2,lung resistanceprotein(LRP), glutathione-S-transferase(GST-π),topoisomeraseⅡ(TopoⅡ),tumor suppressor gene product P53 protein in breast mucinous carcinoma and its clinical significance.
Methods:Immunohistochemistry(LDP) method was used to detect the expressions of ER,PR,Cerb-B2,P53,LRP,GST-π,TopoⅡin 42 cases of mucinous carcinoma of the breast,Statistical analyses were used to study the relationship between the test results and different clinicopathological parameters.
Results:42 cases of mucinous breast cancer,there are 10 cases of lymph node metastasis in patients with mixed mucinous carcinoma of 7 cases,3 cases of pure mucinous carcinoma,The axillary's metastasis node numbers was related to the different histological types,p=0.027,r=0.367;The expressions of ER、PR、Cerb-B2、P53、LRP、GST-π、TopoⅡin this group were 80.9%,85.7%,47.6%,45.2%,85.7%, 64.3%,52.4%respectively;the ER was distinctly related to the different histological types and the expressions of P53,(p＜0.05);the expressions of P53 was related to the expressions of GST-π(p=0.003.r=0.478);LRP was related to GST-π(p=0.008.r=0.406);No relationship was found between P53 and LRP、TopoⅡ; The expressions of TopoⅡwas related the tumor diameter(p=0.03).And no relationship was found between ER、PR、Cerb-B2、TopoⅡ、LRP、GST-π、P53 protein in mucinous carcinoma of the breast and patient's age,menstrual status,axillary lymph node metastasis.
Conclusion:Combined detection of TopoⅡ,LRP,GST-π,P53 protein in mucinous breast carcinoma and analysis of hormone receptor status and clinicopathological factors can help assess the biological behavior of the mucinous breast carcinoma and have important reference value to the chemotherapy and endocrine therapy.
引文
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7.范林军,姜军,赵菲,乳腺粘液癌临床病理特点分析[J],第三军医大学学报2003,25(23):2077-2078。
8.胡薇,施俊义,乳腺粘液癌39例临床特点与预后[J],第二军医大学学报,200728(1):109-111。
9.Barkley CR,Ligibel JA,Wong JS,Mucinous breast carcinoma:a large contemporary series[J],Am J Surg.2008 Oct;196(4):549-51.
10.赵晶,赵广才,刘君,C-erbB-2在乳腺癌中的表达及其15年远期临床意义的分析[J],肿瘤防治研究,2005,32(3):187-188。
11.江学庆,尹美蓉,原癌基因C-erbB-2在乳腺癌中的表达及其临床意义[J],中国普通外科杂志,2008,1.17:502-503。
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13.Borresen-Dale AL:TP53 and breast cancer[J].Hum Mutat 2003,21:292-300
14.阮永威,金星,马宏岩,乳腺癌p53,ki-67和bcl-2的表达与新辅助化疗的关系 [J]. 中国普通外科杂志, 2006, 15 (4) :247-249c
15. Schmit t FC , Leal C , Lopes C. P53 protein expression and nuclear DNA content in breast int roductal proliferation[J],Pat ho , 1995 ,176 :233 - 237.
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19. Rastelli F, Crispino S, Factors predictive of response to hormone therapy in breast cancer [J]. Tumori. 2008 May-Jun;94(3):370-83.
20. Feki A, Irminger-Finger I, Mutational spectrum of p53 mutations in primary breast and ovarian tumors[J], Critical Reviews in Oncology and Hematology 2004, 52: 103-116.
21. Barbareschi M.Prognostic value of the immunohistochemical expression of p53 in breast carcinomas: a review of the literature involving over 9000 patients. Applied Immunohistochemistry [J], 1996,4 :106-116.
22. Borresen-Dale AL. Tp53 and breast cancer[J], Human Mutation,2003, 21 :292-300.
23. Cimoli G, Malacarne D, Ponassi R,Meta-analysis of the role of p53 status inisogenic systems tested for sensitivity to cytotoxic antineoplastic drugs. [J]. Biochim Biophys Acta. 2004 ,17; 1705(2): 103-20.
24. Kandioler-Eckersberger D, Ludwig C, Rudas M, TP53 mutation and p53 over expression for prediction of response to neoadjuvant treatment in breast cancer patients [J], Clin Cancer Res 2000,6:50-56.
25. Meschini S, Marra M, Calcabrini A, Role of the lung resistance cerelated protein(LRP) in the drug sensitivity of cultured tumor cells[J],Toxicol In Vitro,1994,54(8):1325-1327.
26.Izquierdo MA,Scheffer GL,Flens MJ,Broad distribution of the multidrug resistance-related vault lung resistance protein in normal human tissues and tumors.[J],Am J Path,1996,148:877-887.
27.Pohl G,Filipits M,Suchomel RW,Expression of the lung resistance protein(LRP)in primary breast cancer[J],Anticancer Res.1999,19(6B):5051-5.
28.Linn SC,Pinedo HM,van Ark-Otte J,Expression of drug resistance proteins in breast cancer,in relation to chemotherapy[J],I nt J Cancer,1997,71:787-795.
29.Oxide H,Minegishi A,Kobayashis S,Evaluation of p21 and LRP as a factor suggesting breast cancer recurrence[J],NipponGekkai Z asshi,2000,101(2):242244.
30.Abbondanza C,RossiV,Roscigno A,Interaction of vault particles with estrogen receptor in the MCF-7 breast cancer cell.[J],J Cell Biol,1998,141:1301-1310.
31.Huang J,Tan PH,Thiyagarajan J,Prognostic significance of glutathione S transferase-p i in invasive breast cancer[J],ModPathol,2003,16(6):558-565.
32.Soubeyran I,Quenel N,Mauriac L,Variation of hormonal receptor,pS2,C- erb-B2and GST-pi contents in breast carcinomas under tamoxifen:a study of 74cases[J],B r J Cancer,1996,73(6):735-743.
33.曲延刚,邵云霞,乳腺癌LRP、GST-π的表达研究[J],肿瘤研究与临床,200517(4):242-243。
34.J(a|¨)rvinen TA,Kononen J,Pelto-Huikko M,Expression of topoisomerase Ⅱalpha is associated with rapid cell proliferation,aneuploidy,and c-erbB2 overexpression in breast cancer[J],_Am J Pathol.1996 Jun;148(6):2073-82.
35.陈萍,刘新兰,崔洁,GST-π、Topo Ⅱ、ER、PR在乳腺癌组织中的表达及其临床意义[J],宁夏医学杂志2008,30(1):13-15。
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2.Lannigan A K,Going J,WeilerMitho E,Mucinous breast carcinoma[J],The Breast,2002,11(3):359-361.
3.Capella C,Eusebi V,Mann B,et al.Endocrine differentiation in mucoid carcinoma of the breast[J],1 Histopathology,1980,4(6):613-630.
4.Memis A,OzdemirN,Parildar M,et,Mucinous(colloid) breast cancer:mammographic and US features with histologic correlation[J],Eur Radiol,2000,35(1):39-43.
5.Fentiman IS,Millis RR,Smith P,Mucoid breast carcinomas:histology and prognosis[J],Br J Cancer 1997;75:1061-1065.
6.顾林,穆振宇,宁连胜等.女性乳腺粘液腺癌101例临床分析[J],中华普通外科杂志,2002,17:430-431。
7.范林军,姜军,赵菲,乳腺粘液癌临床病理特点分析[J],第三军医大学学报2003,25(23):2077-2078。
8.胡薇,施俊义,乳腺粘液癌39例临床特点与预后[J],第二军医大学学报,200728(1):109-111。
9.Barkley CR,Ligibel JA,Wong JS,Mucinous breast carcinoma:a large contemporary series[J],Am J Surg.2008 Oct;196(4):549-51.
10.赵晶,赵广才,刘君,C-erbB-2在乳腺癌中的表达及其15年远期临床意义的分析[J],肿瘤防治研究,2005,32(3):187-188。
11.江学庆,尹美蓉,原癌基因C-erbB-2在乳腺癌中的表达及其临床意义[J],中国普通外科杂志,2008,1.17:502-503。
12.Marc Lacroix,Robert-Alain Toillon p53 and breast cancer,an update[J],Endocrine- Related Cancer 2006,13:293-325
13.Borresen-Dale AL:TP53 and breast cancer[J].Hum Mutat 2003,21:292-300
14.阮永威,金星,马宏岩,乳腺癌p53,ki-67和bcl-2的表达与新辅助化疗的关系 [J]. 中国普通外科杂志, 2006, 15 (4) :247-249c
15. Schmit t FC , Leal C , Lopes C. P53 protein expression and nuclear DNA content in breast int roductal proliferation[J],Pat ho , 1995 ,176 :233 - 237.
16. LacroixM, Toillon RA,Leclercq G, Stable 'portrait' of breast tumors during progression: data from biology,pathology and genetics.Endocrine-Related,Cancer [J] 2004, 11: 497-522.
17. Sorlie T, Perou CM, Tibshirani R, Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications[J], Proc Natl Acad Sci U SA2001, 98:10869-10874.
18. Rahko E, Blanco G, Bloigu R, Adverse outcome and resistance to adjuvant antiestrogen therapy in node-positive postmenopausal breast cancer patients - the role of p53 [J], Breast. 2006 Feb; 15(1):69-75.
19. Rastelli F, Crispino S, Factors predictive of response to hormone therapy in breast cancer [J]. Tumori. 2008 May-Jun;94(3):370-83.
20. Feki A, Irminger-Finger I, Mutational spectrum of p53 mutations in primary breast and ovarian tumors[J], Critical Reviews in Oncology and Hematology 2004, 52: 103-116.
21. Barbareschi M.Prognostic value of the immunohistochemical expression of p53 in breast carcinomas: a review of the literature involving over 9000 patients. Applied Immunohistochemistry [J], 1996,4 :106-116.
22. Borresen-Dale AL. Tp53 and breast cancer[J], Human Mutation,2003, 21 :292-300.
23. Cimoli G, Malacarne D, Ponassi R,Meta-analysis of the role of p53 status inisogenic systems tested for sensitivity to cytotoxic antineoplastic drugs. [J]. Biochim Biophys Acta. 2004 ,17; 1705(2): 103-20.
24. Kandioler-Eckersberger D, Ludwig C, Rudas M, TP53 mutation and p53 over expression for prediction of response to neoadjuvant treatment in breast cancer patients [J], Clin Cancer Res 2000,6:50-56.
25. Meschini S, Marra M, Calcabrini A, Role of the lung resistance cerelated protein(LRP) in the drug sensitivity of cultured tumor cells[J],Toxicol In Vitro,1994,54(8):1325-1327.
26.Izquierdo MA,Scheffer GL,Flens MJ,Broad distribution of the multidrug resistance-related vault lung resistance protein in normal human tissues and tumors.[J],Am J Path,1996,148:877-887.
27.Pohl G,Filipits M,Suchomel RW,Expression of the lung resistance protein(LRP)in primary breast cancer[J],Anticancer Res.1999,19(6B):5051-5.
28.Linn SC,Pinedo HM,van Ark-Otte J,Expression of drug resistance proteins in breast cancer,in relation to chemotherapy[J],I nt J Cancer,1997,71:787-795.
29.Oxide H,Minegishi A,Kobayashis S,Evaluation of p21 and LRP as a factor suggesting breast cancer recurrence[J],NipponGekkai Z asshi,2000,101(2):242244.
30.Abbondanza C,RossiV,Roscigno A,Interaction of vault particles with estrogen receptor in the MCF-7 breast cancer cell.[J],J Cell Biol,1998,141:1301-1310.
31.Huang J,Tan PH,Thiyagarajan J,Prognostic significance of glutathione S transferase-p i in invasive breast cancer[J],ModPathol,2003,16(6):558-565.
32.Soubeyran I,Quenel N,Mauriac L,Variation of hormonal receptor,pS2,C- erb-B2and GST-pi contents in breast carcinomas under tamoxifen:a study of 74cases[J],B r J Cancer,1996,73(6):735-743.
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