P504S/HMWCK/P63鸡尾酒抗体在前列腺腺癌中的表达及意义
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摘要
目的:利用免疫组织化学染色方法,探讨P504S/HMWCK/P63鸡尾酒抗体,在前列腺癌的诊断及与前列腺上皮内瘤变和不典型腺瘤样增生的鉴别诊断中的意义。
材料和方法:前列腺腺癌44例,包括35例根治手术切除前列腺癌标本和5例经尿道前列腺切除标本(TUR-P),另外,单纯良性前列腺增生5例。前列腺上皮内瘤变分低级别(LGPIN)和高级别(HGPIN)。利用双重免疫组化方法,观察P504S/HMWCK/P63鸡尾酒抗体在前列腺癌和前列腺异型增生病变中的表达。
结果:44例前列腺腺癌病例中,37例(84%)P504S呈弥漫性强阳性,7例(16%)呈灶状阴性,HMWCK/P63在Gleason grade 2和3的癌组织均呈阴性,在11%的Gleasongrade 4和5的癌细胞周围可见阳性表达。在高级别前列腺上皮内瘤变中,P504S呈强阳性,在低级别呈弱阳性或阴性。在高级别前列腺上皮内瘤变周围可见浸润性高分化腺癌。44例癌病例中,有6例可见(6 foci)不典型瘤样增生病变,其中仅一例P504S呈弱阳性,其余呈阴性。在癌症病例中21%的良性腺体呈P504S弱阳性,HMWCK/P6呈阳性。
结论:P504S/HMWCK/P63鸡尾酒抗体对高分化前列腺腺癌,特别是诊断Gleason grade2和3是有效的,首选的抗体,可利用于高分化腺癌和异型增生病变的鉴别诊断。另外,免疫组化染色结果证实高级别前列腺上皮内瘤变是癌前病变,不典型腺瘤样增生可能是良性病变。
Objective: A cocktail of three antibodies, P504S, HMWCK and p63, was applied to the prostate specimens immunohistochemically, and investigated the utilization of the antibody for diagnosing prostatic intraepithelial neoplasia (PIN), and atypical adenomatous hyperplasia (AAH) from true cancer.
Materials and methods: 44 cases of prostate cancer including 39 cases from radical prostatectomy and 5 cases of transurethral resection of prostate (TUR-P), 5 cases of benign prosthetic hyperplasia were reviewed. PIN was observed the point of HGPIN and LGPIN. For to lesion P504S/HMWCK/ p63 were applied using a double-chromogen stain to discriminate the cancer from non-cancer lesions.
Results: Of these 44 cases, 37 (84%) cases were diffuse strongly positive, and 7cases (16%) were focally negative for P504S staining. HMWCK/p63 usually used for demonstrating basal cells were negative in the cases of prostatetic adenocarcinoma with Gleason grade 2 and 3, but interestingly 11% adenocarcinoma with Gleason grade 4 and 5 showed focally or scattered positive. High grade intraepithelial nepplasia (HGPIN) represented moderate to strong positive for P504S, while low grade intraepithelial neoplasia ( LGPIN ) were negative to weak positive. In adjacent to HGPIN, well differentiated adenocarcinoma were often found, and partly showing a sequential change from strong to weak in the same gland. The majority of AAH (5/6 cases) was negative for P504S, but positive for HMWCK/p63. in benign prostatic glands, 21 percent of total cases were faintly positive for P504S and all cases were presented strongly for HMWCK/p63.
Conclusion: Triple antibodies allowed us to easily discriminate the benign atypical lesion from well differentiated adennocarcinoma with Gleason grade 2 and 3 pattern, which has been difficult by usual HE stain and by each antibody separately. It is revealed that HGPIN is proved to be a premalignant lesion strongly associated with carcinoma occurrence by immunohistochemical data as well as histological features. AAH is possibly belongs benigen lesion.
材料和方法:前列腺腺癌44例,包括35例根治手术切除前列腺癌标本和5例经尿道前列腺切除标本(TUR-P),另外,单纯良性前列腺增生5例。前列腺上皮内瘤变分低级别(LGPIN)和高级别(HGPIN)。利用双重免疫组化方法,观察P504S/HMWCK/P63鸡尾酒抗体在前列腺癌和前列腺异型增生病变中的表达。
结果:44例前列腺腺癌病例中,37例(84%)P504S呈弥漫性强阳性,7例(16%)呈灶状阴性,HMWCK/P63在Gleason grade 2和3的癌组织均呈阴性,在11%的Gleasongrade 4和5的癌细胞周围可见阳性表达。在高级别前列腺上皮内瘤变中,P504S呈强阳性,在低级别呈弱阳性或阴性。在高级别前列腺上皮内瘤变周围可见浸润性高分化腺癌。44例癌病例中,有6例可见(6 foci)不典型瘤样增生病变,其中仅一例P504S呈弱阳性,其余呈阴性。在癌症病例中21%的良性腺体呈P504S弱阳性,HMWCK/P6呈阳性。
结论:P504S/HMWCK/P63鸡尾酒抗体对高分化前列腺腺癌,特别是诊断Gleason grade2和3是有效的,首选的抗体,可利用于高分化腺癌和异型增生病变的鉴别诊断。另外,免疫组化染色结果证实高级别前列腺上皮内瘤变是癌前病变,不典型腺瘤样增生可能是良性病变。
Objective: A cocktail of three antibodies, P504S, HMWCK and p63, was applied to the prostate specimens immunohistochemically, and investigated the utilization of the antibody for diagnosing prostatic intraepithelial neoplasia (PIN), and atypical adenomatous hyperplasia (AAH) from true cancer.
Materials and methods: 44 cases of prostate cancer including 39 cases from radical prostatectomy and 5 cases of transurethral resection of prostate (TUR-P), 5 cases of benign prosthetic hyperplasia were reviewed. PIN was observed the point of HGPIN and LGPIN. For to lesion P504S/HMWCK/ p63 were applied using a double-chromogen stain to discriminate the cancer from non-cancer lesions.
Results: Of these 44 cases, 37 (84%) cases were diffuse strongly positive, and 7cases (16%) were focally negative for P504S staining. HMWCK/p63 usually used for demonstrating basal cells were negative in the cases of prostatetic adenocarcinoma with Gleason grade 2 and 3, but interestingly 11% adenocarcinoma with Gleason grade 4 and 5 showed focally or scattered positive. High grade intraepithelial nepplasia (HGPIN) represented moderate to strong positive for P504S, while low grade intraepithelial neoplasia ( LGPIN ) were negative to weak positive. In adjacent to HGPIN, well differentiated adenocarcinoma were often found, and partly showing a sequential change from strong to weak in the same gland. The majority of AAH (5/6 cases) was negative for P504S, but positive for HMWCK/p63. in benign prostatic glands, 21 percent of total cases were faintly positive for P504S and all cases were presented strongly for HMWCK/p63.
Conclusion: Triple antibodies allowed us to easily discriminate the benign atypical lesion from well differentiated adennocarcinoma with Gleason grade 2 and 3 pattern, which has been difficult by usual HE stain and by each antibody separately. It is revealed that HGPIN is proved to be a premalignant lesion strongly associated with carcinoma occurrence by immunohistochemical data as well as histological features. AAH is possibly belongs benigen lesion.
引文
[1]#12
[2]Bostwick DG,Meiers I.Atypical small acinar proliferation in the prostate:clinical singnificance in 2006.Arch Pathol Lab Med,2006,130(7):952-957
[3]Schlesinger C,Bostwick DG,Iczkowski KA.High-grade prostatic intraepithelial neoplasia and atypical small acinar proliferation.Am J Surg Pathol,2005,29(9):1201-1207
[4]Leite KR,Mitteldorf CA,Camara-Lopes LH.Repeat prostate biopsies following diagnoses of prostate intraepithelial neoplasia and atypical small gland proliferation.Int Braz J Urol,2005,31(2):131-136
[5]Jiang Z,Li C,Fischer A,et al.Using anAMACR(p504S)/34betaE12/p63 cocktail for the detection of small focal prostate carcinoma in needle biopsy specimens.Am J Clin Pathol,2005,123(2):231-236
[6]Yu T,Zhu SX,Zheng S,et al.Detection of AMACR(P504S),P63 and 34betaE12cocktail in the early diagnosis of prostate cancer.Zhonghua Nan Ke xue,2007,13(3):222-225
[7]Herawi M,Epstein JI.Immunohistochemical antibody cocktail staining (p63/HMWCK/AMACR) of ductal adenocarcinoma and Gleason patten 4 cribriiform and noncribriform acinar adenocarcinoma of the prostate.Am J Surg Pathol,2007,31(6):889-894
[8]Zhou M,Jiang A,Epstein JI.Expression and diagnostic utility of Alpha-Methylacyl -CoA-Racemase(P504S) in foamy gland and pseudohyperplastic prostate cancer.Am J Surg Pathol,2003,27(6):772-778
[9]Zhou M,Aydin H,kanane H,Epstein JI.How often does Alpha-Methylacyl-CoA-Racemase contributes to resolving an atypical diagnosis on prostate needle biopsy beyond that provided by basal cell markers? Am J Surg pathol,2004,28(2):239-243
[10]Jiang Z,Woda BA,Rock KL,et al.P504S A new molecular marker for the detection of prostate carcinoma.Am J Surg Pathol,2001,25(11):1397-1404
[11] ZhouM. ChinnaiyanAM, KleerCG, et al. Alpha-Methylacyl-CoA-Racemase: anovel tumor marker over-expressed in several human cancers and their precursor lesion. Am J Surg Pathol,2002,26(7): 926-931
[12] Wu CL, Yang XJ, Tretiakova M, et al. Analysis of α-methylayl-CoA racemase (P504S) expression in high-grade prostatic intraepithelial neoplasia. Human Pathology,2004,35:1008-1013
[13] Hepap B. The significance of the P504S expression pattern of high-grade prostatic intraepithelaial neoplasia (HGPIN) with and without adenocarcinoma of the prostate in biopsy and radical prostectomy specimens. Virchows Arch,2006,448:481-484
[14] Ananthanrayanan V, Deaton RJ, Yang XJ, et al. Alpha-Methylacyl-CoA-Racemase (AMACR) expression in normal prostatic glands and high-grade prostatic intraepithelial neoplasia (HGPIN): association with diagnosis of prostate cancer. The prostate, 2005, 63:341-346
[15] Ayala AG, Ro JY. Prostatic intraepithelial neoplasia: recent advances. Arch Pathol Lab Med,2007,131(8): 1257-1266
[16] Yang XJ, Wu CL, Woda BA, et al. Expression of α-methylacyl-coa racemase (P504S) in atypical adenomatous hyperplasia of the prostate. Am J Surg Pathol,2002,26(7):921-925
[17] Flury AC, Galgano MT, Mills SE, et al. Atypical small acinar proliferation: biopsy artefact or distinct pathological entity? BJU Inter, 2007, 99(4): 780-785
[18] Shah RB, Kunju LP, Shen R, et al. Usefulness of basal cell cocktail (34betaE12+p63) in the diagnosis of atypical orostate glandular proliferation. Am J Clin Pathol, 2004,122(4): 517-523
[19] Zhou M, Shah R, Shen R, et al. Basal cell cocktail (34betaE12+p63) improves the detection of prostate basal cells. Am J Surg pathol, 2003,27(3): 365-371
[20] Gologan A, Bastacky S, McHale T, et al. Age-associated changes in Alpha-methyl CoA Racemase (AMACR) expression in nonneoplastic prosthetic tissues. Am J Surg Pathol, 2005,29(11): 1435-1441
[21] Iczkowski KA. Current prostate biopsy interpretation: criteria for cancer, atypical small acinar proloferation, High-grade prostatic intraepithelial neoplasia, and use of immunostains. Arch pathol Lab Med, 2006, 130(6): 835-843
[22] Molinie V, Fromont G, Sibony M, et al. Diagnostic utility of a p63/a-methylacyl coa racemase(P504S) cocktail in atypical foci in the prostate.Mod Pathology,2004,17(10):1180-1190
[23]张洁,李小静,朱卫,等.前列腺癌P504S,p63及CK34βE12表达的研究.肿瘤,2007.(3):227-230
[24]张贵旺,魏学斌,徐留玉,等.P504S,CK34βE12在前列腺癌组织中的表达及意义.山东医药,2007,(8);69-70
[25]刘英娜,蒋智铭,王小亚.AMACR/34βE12/p63鸡尾酒双染对诊断前列腺癌及癌前病变的价值.中华病理学杂志,2006,(7):417-420
[26]Sung MT,Jiang Z,Montironi R,et al.α-methylacyl-CoA racemase(P504S)/34βE12/p63 triple cocktail stain in prostatic adenocarcinoma after hormonal therapy.Human pathology,2007,2:332-341
[27]McNeal JE,Bostwick DG:Intraductal dysplasia:a premalignant lesion of the prostate.Hum Pathol,1986,17:64-71
[28]Oyasu R,Bahnson RR,Nowels K et al:Cytological atypia in the prostate gland:Frequency,distribution and possible relevance to carcinoma.J Uro,1986,135:959-962
[1] Ahmedin Jemal, Rebecca Siegel, Elizabeth Ward, et al.Cancer Statistics, 2007[J].CA Cancer JClin, 2007, 57:43-66.
[2]Karan D, Lin MF, Johansson SL, et al. Current status of the molecular genetics of human prostatic adenocarcinomas [J]. Int J Cancer, 2003, 103(3) :285-293.
[3] Steiner MS, Anthony CT, Lu Y, et al. Antisense c2myc retroviral vector suppresses established human prostate cancer [J]. Hum Gene Ther, 1998, 9 (5) :747-755.
[4] Catz SD, Johnson JL. BCL22 in prostate cancer : a minireview[J]. Apop2 tosis, 2003,8 (1) :29-37.
[5] Sonnemann J, Gekeler V, Sagrauske A, et al. Apoptotic responsiveness of PC23 prostate cancer cells to tumor necrosis factor2related apoptosis2 inducing ligand : evidence for differential effects of Bcl2xL and Bcl22 down2regulation[J]. Int J Oncol, 2004,25(4) :1171-1181.
[6] Edwards J, Krishna NS, Witton CJ, et al. Gene amplifications associated with the development of hormone2resistant prostate cancer [J]. Clin Cancer Res, 2003,9(14) :5271-5281.
[7] Degeorges A, Iioffschir F, Cussenot O, et al. Recurrent cyto genetic al2 terations of prostate carcinoma and amplification of c2myc or epidermal growth factor receptor in subciones of immortalized PNT1 human prosta2 teepithelial cellline[J]. Int J Cancer,1995, 62(6):724.
[8] Bastacky S, Cieply K, Sherer C, et al. Use of interphase fluorescence insitu hybridization in prostate needle biopsy specimens with isolated high2grade prostatic intraepithelial neoplasia as a predictor of prostate adenocarcinoma on folio w2up biopsy [J].Hum Pathol, 2004, 35(3) :281-289.
[9] Bernard D, Pourtier2Manzanedo A, Gil J, et al. Myc confers androgen2 independent prostate cancer cell growth [J]. J Clin Invest, 2003, 112(11) :1724-1731.
[10] Karan D, Lin MF, Johansson SL, et al. Current status of the molecular genetics of human prostatic adenocarcinomas [J]. Int J Cancer, 2003, 103(3) :285-293.
[11] Catz SD, Johnson JL.BCL-2 in prostate cancer :a minireview[J]. Apop2 tosis, 2003,8 (1) :29-37.
[12] Steiner MS, Anthony CT, Lu Y, et al. Antisense c-myc retroviral vector suppresses established human prostate cancer [J]. Hum Gene Ther, 1998, 9(5):747-755.
[13] Weber MJ, Gioeli D. Ras signaling in prostate cancer progression[J]. J Cell Biochem,2004, 91 (1) :13-25.
[14] Bakin RE, Gioeli D, Sikes RA, et al. Constitutive activation of the rasp mitogen-activated protein kinase signaling pathway promotes androgen hypersensitivity in LNCaP prostate cancer cells[J]. Cancer Res, 2003, 63(8) :1981-1989.
[15] Dean NM, Bennett CF. Antisense oligonucleotide2based therapeutics for cancer[J].Oncogene, 2003, 22 (56) :9087-9096.
[16] Iversen PL, Arora V, Acker A J, et al. Efficacy of antisense morpholino oligomer targeted to c2myc in prostate cancer xenograft murine model and a Phase I safety study in humans [J] . Clin Cancer Res, 2003, 9(7) :2510-2519.
[17] Peter B, Howard A, Mannuela C, et al. Therapy for pancreatic cancer with a recombinant humanizied antibody anti2HER2(Hercepitin) [J]. J Gastrointestinal Surgery, 2001, 31 (5) :139-141.
[18]于力,韩为东,楼方定,等. 新的白血病相关基因LRP16的克隆[J].军医进修学学报, 2000 , 21(2):81-84.
[19]Han WD, Mu YM, Lu XC, et al. Up-regulation of LRP16 mRNA by 17β2estradiol through activation of estrogen receptora( ERα), but not ERβand promotion of human breast cancer MCF-7 cell proliferation :a preliminary report [J] . Endocrine-Related Cancer, 2003, 10 (2): 217-224.
[20] Scott A, Tomlin S, Daniel R, et al. Recurrent fusion of TMPRSS2 and ETS rtanscription factor genes in prostate cancer [J]. Science, 2005, 310(5748) :644-648
[21] Sun Y, Lin J, Katz AE, et al. Human prostatic carcinoma oncogene PTI-lisexpressed in human tumor celllines and prostate carcinorma patient blood samples[J]. Cancer Res, 1997, 57(1) :18-23.
[22] Gopalkrishnan RV, Su ZZ, Goldstein NI, et al. Translation an infidelity and human cancer : role of the PTI 1oncogene [J]. Int J Biochem Cell Biol, 1999, 31 (1):151-622.
[23] Bastacky S, Cieply K, Sherer C, et al. Use of interphase fluorescence in situ hybridization in prostate needle biopsy specimens with isolated high-grade prostatic intraepithelial neoplasia as a predictor of prostate adenocarcinoma on follow-up biopsy [J].Hum Pathol, 2004, 35 (3) :281-289.
[24] Sonnemann J, Gekeler V, Sagrauske A, et al. Apoptotic responsiveness of PC23 prostate cancer cells to tumor necrosis factor-related apoptosis-inducing ligand :evidence for differential effects of Bcl-xL and Bcl-2down-regulation[J] . Int J Oncol,2004, 25(4):1171-1181
[25] Li J, Yen C, Liaw D, et al. PTEN, a putative protein tyrosine phosphor-tase gene muted in human brain , breast and prostated cancer [J]. Sci-ence, 1997, 275(2) :1943-1947.
[26] GeorgescuMM, Kirsch KH, Akagi T, et al. The tumor suppressor active- ty of PTEN is regulated by its carboxyl terminal region [J]. Proc Natl Acad Sci USA, 1998, 98(10):1822-1831.
[27] Bandyopadhyay S, Pai SK, Watabe M, et al. FAS expression inversely correlates with PTEN level in prostate cancer and a PI 3-kinase inhibit- for synergizes with FAS siRNA to induce apoptosis [J]. Oncogene, 2005, 24 (3) :945-951.
[28] Marx J. New tumor suppressor may rival p53 [J]. Science, 1994, 264 (2) :344-345.
[29] Degeorges A, Iioffschir F, Cussenot O, et al. Recurrent cyto genetic al- terations of prostate carcinoma and amplification of c-myc or epidermal growth factor receptor in subciones of immortalized PNT1 human prosta- te epithelial cellline[J]. Int J Cancer,1995, 62(6):724.
[30] Maddison LA, Sutherland BW, Barrios RJ, et al. Conditional deletionof Rb causes early stage prostate cancer[J ]. Cancer Res, 2004, 64 (17): 6018-6025.
[31] Narla G, Heath KE, Reeves HL, et al. KLF6, acandidate tumor sup- pressor gene mutated in prostate cancer [J] . Science, 2001, 294 (15): 2563-2566.
[32] Dammann R, LiC, Yoon JH, et al. Epigenetic inactivatio of a ras associ- ation domain family protein fromthe lung tumour suppressor Iocus3p21. 3[J]. Nat Genet, 2000, 25(3) :315-319.
[33] Liu L, Yoon JH, Dammann R, et al. Frequent hypermetylation of the Ras SF1A gene in prostate cancer [J]. Oncogene, 2002, 21 (44) :6835- 6840.
[2]Bostwick DG,Meiers I.Atypical small acinar proliferation in the prostate:clinical singnificance in 2006.Arch Pathol Lab Med,2006,130(7):952-957
[3]Schlesinger C,Bostwick DG,Iczkowski KA.High-grade prostatic intraepithelial neoplasia and atypical small acinar proliferation.Am J Surg Pathol,2005,29(9):1201-1207
[4]Leite KR,Mitteldorf CA,Camara-Lopes LH.Repeat prostate biopsies following diagnoses of prostate intraepithelial neoplasia and atypical small gland proliferation.Int Braz J Urol,2005,31(2):131-136
[5]Jiang Z,Li C,Fischer A,et al.Using anAMACR(p504S)/34betaE12/p63 cocktail for the detection of small focal prostate carcinoma in needle biopsy specimens.Am J Clin Pathol,2005,123(2):231-236
[6]Yu T,Zhu SX,Zheng S,et al.Detection of AMACR(P504S),P63 and 34betaE12cocktail in the early diagnosis of prostate cancer.Zhonghua Nan Ke xue,2007,13(3):222-225
[7]Herawi M,Epstein JI.Immunohistochemical antibody cocktail staining (p63/HMWCK/AMACR) of ductal adenocarcinoma and Gleason patten 4 cribriiform and noncribriform acinar adenocarcinoma of the prostate.Am J Surg Pathol,2007,31(6):889-894
[8]Zhou M,Jiang A,Epstein JI.Expression and diagnostic utility of Alpha-Methylacyl -CoA-Racemase(P504S) in foamy gland and pseudohyperplastic prostate cancer.Am J Surg Pathol,2003,27(6):772-778
[9]Zhou M,Aydin H,kanane H,Epstein JI.How often does Alpha-Methylacyl-CoA-Racemase contributes to resolving an atypical diagnosis on prostate needle biopsy beyond that provided by basal cell markers? Am J Surg pathol,2004,28(2):239-243
[10]Jiang Z,Woda BA,Rock KL,et al.P504S A new molecular marker for the detection of prostate carcinoma.Am J Surg Pathol,2001,25(11):1397-1404
[11] ZhouM. ChinnaiyanAM, KleerCG, et al. Alpha-Methylacyl-CoA-Racemase: anovel tumor marker over-expressed in several human cancers and their precursor lesion. Am J Surg Pathol,2002,26(7): 926-931
[12] Wu CL, Yang XJ, Tretiakova M, et al. Analysis of α-methylayl-CoA racemase (P504S) expression in high-grade prostatic intraepithelial neoplasia. Human Pathology,2004,35:1008-1013
[13] Hepap B. The significance of the P504S expression pattern of high-grade prostatic intraepithelaial neoplasia (HGPIN) with and without adenocarcinoma of the prostate in biopsy and radical prostectomy specimens. Virchows Arch,2006,448:481-484
[14] Ananthanrayanan V, Deaton RJ, Yang XJ, et al. Alpha-Methylacyl-CoA-Racemase (AMACR) expression in normal prostatic glands and high-grade prostatic intraepithelial neoplasia (HGPIN): association with diagnosis of prostate cancer. The prostate, 2005, 63:341-346
[15] Ayala AG, Ro JY. Prostatic intraepithelial neoplasia: recent advances. Arch Pathol Lab Med,2007,131(8): 1257-1266
[16] Yang XJ, Wu CL, Woda BA, et al. Expression of α-methylacyl-coa racemase (P504S) in atypical adenomatous hyperplasia of the prostate. Am J Surg Pathol,2002,26(7):921-925
[17] Flury AC, Galgano MT, Mills SE, et al. Atypical small acinar proliferation: biopsy artefact or distinct pathological entity? BJU Inter, 2007, 99(4): 780-785
[18] Shah RB, Kunju LP, Shen R, et al. Usefulness of basal cell cocktail (34betaE12+p63) in the diagnosis of atypical orostate glandular proliferation. Am J Clin Pathol, 2004,122(4): 517-523
[19] Zhou M, Shah R, Shen R, et al. Basal cell cocktail (34betaE12+p63) improves the detection of prostate basal cells. Am J Surg pathol, 2003,27(3): 365-371
[20] Gologan A, Bastacky S, McHale T, et al. Age-associated changes in Alpha-methyl CoA Racemase (AMACR) expression in nonneoplastic prosthetic tissues. Am J Surg Pathol, 2005,29(11): 1435-1441
[21] Iczkowski KA. Current prostate biopsy interpretation: criteria for cancer, atypical small acinar proloferation, High-grade prostatic intraepithelial neoplasia, and use of immunostains. Arch pathol Lab Med, 2006, 130(6): 835-843
[22] Molinie V, Fromont G, Sibony M, et al. Diagnostic utility of a p63/a-methylacyl coa racemase(P504S) cocktail in atypical foci in the prostate.Mod Pathology,2004,17(10):1180-1190
[23]张洁,李小静,朱卫,等.前列腺癌P504S,p63及CK34βE12表达的研究.肿瘤,2007.(3):227-230
[24]张贵旺,魏学斌,徐留玉,等.P504S,CK34βE12在前列腺癌组织中的表达及意义.山东医药,2007,(8);69-70
[25]刘英娜,蒋智铭,王小亚.AMACR/34βE12/p63鸡尾酒双染对诊断前列腺癌及癌前病变的价值.中华病理学杂志,2006,(7):417-420
[26]Sung MT,Jiang Z,Montironi R,et al.α-methylacyl-CoA racemase(P504S)/34βE12/p63 triple cocktail stain in prostatic adenocarcinoma after hormonal therapy.Human pathology,2007,2:332-341
[27]McNeal JE,Bostwick DG:Intraductal dysplasia:a premalignant lesion of the prostate.Hum Pathol,1986,17:64-71
[28]Oyasu R,Bahnson RR,Nowels K et al:Cytological atypia in the prostate gland:Frequency,distribution and possible relevance to carcinoma.J Uro,1986,135:959-962
[1] Ahmedin Jemal, Rebecca Siegel, Elizabeth Ward, et al.Cancer Statistics, 2007[J].CA Cancer JClin, 2007, 57:43-66.
[2]Karan D, Lin MF, Johansson SL, et al. Current status of the molecular genetics of human prostatic adenocarcinomas [J]. Int J Cancer, 2003, 103(3) :285-293.
[3] Steiner MS, Anthony CT, Lu Y, et al. Antisense c2myc retroviral vector suppresses established human prostate cancer [J]. Hum Gene Ther, 1998, 9 (5) :747-755.
[4] Catz SD, Johnson JL. BCL22 in prostate cancer : a minireview[J]. Apop2 tosis, 2003,8 (1) :29-37.
[5] Sonnemann J, Gekeler V, Sagrauske A, et al. Apoptotic responsiveness of PC23 prostate cancer cells to tumor necrosis factor2related apoptosis2 inducing ligand : evidence for differential effects of Bcl2xL and Bcl22 down2regulation[J]. Int J Oncol, 2004,25(4) :1171-1181.
[6] Edwards J, Krishna NS, Witton CJ, et al. Gene amplifications associated with the development of hormone2resistant prostate cancer [J]. Clin Cancer Res, 2003,9(14) :5271-5281.
[7] Degeorges A, Iioffschir F, Cussenot O, et al. Recurrent cyto genetic al2 terations of prostate carcinoma and amplification of c2myc or epidermal growth factor receptor in subciones of immortalized PNT1 human prosta2 teepithelial cellline[J]. Int J Cancer,1995, 62(6):724.
[8] Bastacky S, Cieply K, Sherer C, et al. Use of interphase fluorescence insitu hybridization in prostate needle biopsy specimens with isolated high2grade prostatic intraepithelial neoplasia as a predictor of prostate adenocarcinoma on folio w2up biopsy [J].Hum Pathol, 2004, 35(3) :281-289.
[9] Bernard D, Pourtier2Manzanedo A, Gil J, et al. Myc confers androgen2 independent prostate cancer cell growth [J]. J Clin Invest, 2003, 112(11) :1724-1731.
[10] Karan D, Lin MF, Johansson SL, et al. Current status of the molecular genetics of human prostatic adenocarcinomas [J]. Int J Cancer, 2003, 103(3) :285-293.
[11] Catz SD, Johnson JL.BCL-2 in prostate cancer :a minireview[J]. Apop2 tosis, 2003,8 (1) :29-37.
[12] Steiner MS, Anthony CT, Lu Y, et al. Antisense c-myc retroviral vector suppresses established human prostate cancer [J]. Hum Gene Ther, 1998, 9(5):747-755.
[13] Weber MJ, Gioeli D. Ras signaling in prostate cancer progression[J]. J Cell Biochem,2004, 91 (1) :13-25.
[14] Bakin RE, Gioeli D, Sikes RA, et al. Constitutive activation of the rasp mitogen-activated protein kinase signaling pathway promotes androgen hypersensitivity in LNCaP prostate cancer cells[J]. Cancer Res, 2003, 63(8) :1981-1989.
[15] Dean NM, Bennett CF. Antisense oligonucleotide2based therapeutics for cancer[J].Oncogene, 2003, 22 (56) :9087-9096.
[16] Iversen PL, Arora V, Acker A J, et al. Efficacy of antisense morpholino oligomer targeted to c2myc in prostate cancer xenograft murine model and a Phase I safety study in humans [J] . Clin Cancer Res, 2003, 9(7) :2510-2519.
[17] Peter B, Howard A, Mannuela C, et al. Therapy for pancreatic cancer with a recombinant humanizied antibody anti2HER2(Hercepitin) [J]. J Gastrointestinal Surgery, 2001, 31 (5) :139-141.
[18]于力,韩为东,楼方定,等. 新的白血病相关基因LRP16的克隆[J].军医进修学学报, 2000 , 21(2):81-84.
[19]Han WD, Mu YM, Lu XC, et al. Up-regulation of LRP16 mRNA by 17β2estradiol through activation of estrogen receptora( ERα), but not ERβand promotion of human breast cancer MCF-7 cell proliferation :a preliminary report [J] . Endocrine-Related Cancer, 2003, 10 (2): 217-224.
[20] Scott A, Tomlin S, Daniel R, et al. Recurrent fusion of TMPRSS2 and ETS rtanscription factor genes in prostate cancer [J]. Science, 2005, 310(5748) :644-648
[21] Sun Y, Lin J, Katz AE, et al. Human prostatic carcinoma oncogene PTI-lisexpressed in human tumor celllines and prostate carcinorma patient blood samples[J]. Cancer Res, 1997, 57(1) :18-23.
[22] Gopalkrishnan RV, Su ZZ, Goldstein NI, et al. Translation an infidelity and human cancer : role of the PTI 1oncogene [J]. Int J Biochem Cell Biol, 1999, 31 (1):151-622.
[23] Bastacky S, Cieply K, Sherer C, et al. Use of interphase fluorescence in situ hybridization in prostate needle biopsy specimens with isolated high-grade prostatic intraepithelial neoplasia as a predictor of prostate adenocarcinoma on follow-up biopsy [J].Hum Pathol, 2004, 35 (3) :281-289.
[24] Sonnemann J, Gekeler V, Sagrauske A, et al. Apoptotic responsiveness of PC23 prostate cancer cells to tumor necrosis factor-related apoptosis-inducing ligand :evidence for differential effects of Bcl-xL and Bcl-2down-regulation[J] . Int J Oncol,2004, 25(4):1171-1181
[25] Li J, Yen C, Liaw D, et al. PTEN, a putative protein tyrosine phosphor-tase gene muted in human brain , breast and prostated cancer [J]. Sci-ence, 1997, 275(2) :1943-1947.
[26] GeorgescuMM, Kirsch KH, Akagi T, et al. The tumor suppressor active- ty of PTEN is regulated by its carboxyl terminal region [J]. Proc Natl Acad Sci USA, 1998, 98(10):1822-1831.
[27] Bandyopadhyay S, Pai SK, Watabe M, et al. FAS expression inversely correlates with PTEN level in prostate cancer and a PI 3-kinase inhibit- for synergizes with FAS siRNA to induce apoptosis [J]. Oncogene, 2005, 24 (3) :945-951.
[28] Marx J. New tumor suppressor may rival p53 [J]. Science, 1994, 264 (2) :344-345.
[29] Degeorges A, Iioffschir F, Cussenot O, et al. Recurrent cyto genetic al- terations of prostate carcinoma and amplification of c-myc or epidermal growth factor receptor in subciones of immortalized PNT1 human prosta- te epithelial cellline[J]. Int J Cancer,1995, 62(6):724.
[30] Maddison LA, Sutherland BW, Barrios RJ, et al. Conditional deletionof Rb causes early stage prostate cancer[J ]. Cancer Res, 2004, 64 (17): 6018-6025.
[31] Narla G, Heath KE, Reeves HL, et al. KLF6, acandidate tumor sup- pressor gene mutated in prostate cancer [J] . Science, 2001, 294 (15): 2563-2566.
[32] Dammann R, LiC, Yoon JH, et al. Epigenetic inactivatio of a ras associ- ation domain family protein fromthe lung tumour suppressor Iocus3p21. 3[J]. Nat Genet, 2000, 25(3) :315-319.
[33] Liu L, Yoon JH, Dammann R, et al. Frequent hypermetylation of the Ras SF1A gene in prostate cancer [J]. Oncogene, 2002, 21 (44) :6835- 6840.