良性前列腺增生患者血清前列腺特异性抗原升高的病理学研究
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摘要
研究背景：
良性前列腺增生症(benign prostatic hyperplasia，BPH)是50岁以上男性的常见病，但前列腺癌(prostate carcinoma，PCa)亦易发于这一人群。因此，早期诊断和鉴别诊断具有十分重要的意义。近十年来，血清前列腺特异性抗原(prostate specfic antigen，PSA)已成为临床研究和应用最广泛的一种前列腺癌瘤标，具有对前列腺癌筛选的敏感性、特异性，并对前列腺癌体积大小、分期、分级和治疗选择、疗效判断、预后估计及监测具有相当的临床价值。
正常男性的血清PSA＜4 ng·ml~(-1)，昼夜变化极小。BPH与PCa患病年龄相同，均可使PSA升高。但两者分泌PSA的方式不同，使血清PSA有着较大差异。临床80％的PCa血清PSA＞4 ng·ml~(-1)。而BPH患者除年龄因素外，主要是由于腺体上皮组织增生和体积增大，血清PSA轻度增高，大多仍在正常范围(＜4 ng·ml~(-1))，但临床上可见有部分患者血清PSA不同程度升高，Hudson等报道有2％～3％的BPH患者血清PSA≥10ng·ml~(-1)。单从上述生理因素角度不足以解释，目前也尚无相关报道。
目前发现影响血清PSA的因素除上述外，雄激素及射精等生理因素也可影响PSA浓度。前列腺按摩、前列腺活检或TURP等医源性因素可使血清PSA明显上升。此外，经直肠B超检查、膀胱镜检查、尿潴留及细菌性前列腺炎症等因素亦可能会影响PSA的水平。上述除生理因素影响外，前列腺炎症可持续作用而影响前列腺腺体周围环境。那么，临床上所见血清PSA异常升高的BPH患者，是否为因同时有前列腺炎症影响所致呢?
鉴于对前列腺癌的诊断、鉴别诊断及治疗的要求，提高PSA作为其瘤标的敏感性和特异性，本课题对经病理证实的172例BPH患者前列腺标本切片进行分析研究，以期发现BPH患者血清PSA升高的原因，并探讨其发生机制。
研究目的：
本课题拟对经病理证实的172例BPH患者手术切除的前列腺组织标本切片分析研究，应用HE染色和免疫组化技术PSA染色，从而发现血清PSA升高的BPH患者前
列腺腺体的变化，以及PSA在前列腺的分泌和表达的改变，探讨其升高的病因和机制。
方法:
1、HE染色
切片于二甲苯中脱蜡，梯度酒精脱蜡水化，Lillie Maye:氏苏木素染色，1%盐酸
乙醇溶液分化，自来水冲洗，伊红染色;再用自来水冲洗，分色。梯度酒精脱水，石
碳酸二甲苯透明，中性树胶封片。
2、PSA染色
10%缓冲中性甲醛固定，常规脱水、透明、浸蜡、包埋，切片厚1.5一Zpm，二甲
苯中脱蜡，梯度酒精脱蜡水化，3%HZOZ处理，PBS冲洗;抗原修复，PBS冲洗;多
聚赖氨酸贴附，用PBS代替一抗作阴性对照。经微波炉92一98’C 10min进行处理，滴
加一抗和二抗，PBS冲洗;DAB显色，苏木素复染，常规脱水、透明、封片。
3、血清PSA检测
血清PSA采用放射免疫分析法，于术前晨6一7时采静脉血Zml(采血前均未服用
5。一还原酶抑制剂及其它内分泌药物，2周避免尿道内操作及直肠指检)，分离血清后
用进行检测，采用美国Beckman公司生产的全自动化学发光免疫仪及其相应试剂盒。
4、前列腺体积测定
经直肠B超测定前列腺上下径(DI)、前后径(DZ)和左右径(D3)，前列腺体积
(v)采用近似长椭球体公式v=二/6XD，只nZxo3(cm3)计算。
5、统计分析
172例患者按血清PsA值分3组:A组<4ng·ml一‘;B组)4一 组)10ng’ ml一’。病理诊断慢性前列腺炎以多灶性炎为标准，其主要来源为T淋巴细
胞。每组按HE染色、PSA染色标本见有无多灶性淋巴细胞浸润分为1组和2组。血
清PSA数据用SPSSH.O软件进行单因素方差分析和行x列x“检验分析，均数采用尤
士:表示，以尸<0.05为有显著性差异。
实验结果:
1、单纯间质性炎淋巴细胞浸润，如无腺上皮区的破坏，血清PSA在正常范围。
2、炎症或其他因素累及腺上皮可致血清PSA升高，前列腺腺体破坏程度愈大，
血清PSA升高愈明显。
3、血清PSA水平改变与是否合并慢性前列腺炎无相关性，炎症影响为非特异性。
4、血清PSA妻1ong’ ml-l者，免疫组化显示其前列腺间质以及血管中有染色的
PsA抗原，4ng·ml一，生血清PsA<10ng’ mr’者前列腺间质及血管偶可见PsA染色，
而血清PsA<4ng’ ml一’者则无。
结论:
1、支持“渗漏学说”:当BPH患者腺体受各种因素影响导致扩张、破坏时，PSA
渗漏入间质，继而进入血液循环，血清 PSA明显升高。
2、腺体破坏程度决定血清PSA升高程度。
Baekground:
Benign Prostatic hyPerplasia(BPH)15 a common disease in male more than 50 years
old，and eareinoma of Prostate(PCa)15 also easy to haPPen in the erowd.Therefore，early
diagnosis and differential diagnosis are imPortant significanee.From the 10 years reeently，
Prostate sPecfie antigen(PSA)in blood serum has already been the widest mark of PCa in
clinieal study and aPPlication，whieh have the sensibility and sPeeifieity for PCa screening
and whieh are eorresPonding elinieal value to judging PCa size，staging and grading，to
seleeting PCa treatment，to judging therapeutie effeet and to estimating and monitoring
Pfogn0SIS.
The serum PsA of the common ma一e 15 less than 4 ng·ml.l，whose diurual variation 15
tiny.BPH and PCa，5 serum PSA are rising，whose age with disease are in eonformity.Their
excreting PSA ways are also different，which make the serunn PSA level disParated.80
percents of Pea serum PsA in elinic are more出an 4 ng·ml’1.HowevertheserumPsAof
BPH Patients are lighely rising because of their gland ePithelial tissue hyPerblastosis and
volume augmentation Primarily exeePt for their ages，and the major are in normal range(<4
ng·ml’l).But the serum PsA ofthe partial ones are rising disparitly.Aeeording to Hudson;s
rePorts， there are about 2 or 3 Pereents of the Patienis that their serum PSA are more than
long·ml’1，whieh eouldn，t be enough to be explained only on the above一mentioned
Physiologie factor’5 Point of view.And now there are not eorrelated rePorts.
ExcePt the above一mentioned factors that are able to effect the serum PSA as yet，
androgen and ejaeulation also may effect the density of PSA.The iatrogenie factors，for
examPle，Prostatic massage，Prostate bioPsy and TURP，may make the serum PSA rise
obviously.In addition，the Per reetum tyPe一B ultrasonie，eystoscoPe eheek，uroschesis and
bacteral Prostatitis ete，maybe influence the lever of PSA.Among the above一mentioned
factors excePt for the Physiologic ones，Prostatitis can Persistently effect the environment of
Prostate gland.Then whether or not that 15 the reason of the serurn PSA rising that BPH
Patients are with Prostatitis?
In view of the requirement to diagnose，differential diagnosis and treatment of PCa，
raising the PSA’5 sensitivity and sPecifieity as the tumorous mark，the toPie analyzes and
studies the 1 72 BPH patients’prostate specimen sliees whieh have been verificated on
Pathology.Form this we hoPe that we ean find out the reason of the BPH Patienis’serum
PSA rising and investigate the meehanisms.
objeetives
The toPie will analyze and study the 1 72 BPH Patienis’Prostate exairesis sPeeimen
sliees whieh have been verifieated on Pathology，HE dyeing and PSA
immunohistoehemistry dyeing utilized.Then we ean find out the variation of BPH Patients’
Prostate gland when the serurn PSArising，and ehanges of PSA seeretion and exPression on
Prostate，from whieh we eould investigate the etioPathogenisis and the meehanisms.
Methods:
l、HE dyeing
Sliee deParaffinaged in xylol，hydrated in gradieni aleohol，dyeing in Lillie Mayer
hematoxylin staining solution，differentiated inl%liquor of hydroehlorie aeid and aleohol，
flushed with water，dyeing eosine staining solution，flushed with water again，seParating
eolor.gradieni aleoholie dehydrated，the mixed liquor of fenol and xylol eleared，neutral
gurn mounied.
2、PSA dyeing
10%buffering neutral formalin fixed;routine arthydration，elearing，immerse wax，
embedding;1 .5一2 p m slice stretehed，sliee deParaffinaged in xylol，hydrated in gradieni
alcohol，dealed with3%hydrogen Peroxide，rinsed with PBS，antlgen restored，rinsed with
PBS again，attached with Polylysine，negative eontrolled with PBS rePlaeed of monantigen.
Dealed with mierowave oven for 1 0 minutes in 92一98oC，monantigen and diPlantigen
droPwised，rinsed with PBS again，eolourated with DAB，afterstained with hematoxylin.
routine dePrivated，elearing，mounting.
二
3 the serum PSA detection
Detection with radio
良性前列腺增生症(benign prostatic hyperplasia，BPH)是50岁以上男性的常见病，但前列腺癌(prostate carcinoma，PCa)亦易发于这一人群。因此，早期诊断和鉴别诊断具有十分重要的意义。近十年来，血清前列腺特异性抗原(prostate specfic antigen，PSA)已成为临床研究和应用最广泛的一种前列腺癌瘤标，具有对前列腺癌筛选的敏感性、特异性，并对前列腺癌体积大小、分期、分级和治疗选择、疗效判断、预后估计及监测具有相当的临床价值。
正常男性的血清PSA＜4 ng·ml~(-1)，昼夜变化极小。BPH与PCa患病年龄相同，均可使PSA升高。但两者分泌PSA的方式不同，使血清PSA有着较大差异。临床80％的PCa血清PSA＞4 ng·ml~(-1)。而BPH患者除年龄因素外，主要是由于腺体上皮组织增生和体积增大，血清PSA轻度增高，大多仍在正常范围(＜4 ng·ml~(-1))，但临床上可见有部分患者血清PSA不同程度升高，Hudson等报道有2％～3％的BPH患者血清PSA≥10ng·ml~(-1)。单从上述生理因素角度不足以解释，目前也尚无相关报道。
目前发现影响血清PSA的因素除上述外，雄激素及射精等生理因素也可影响PSA浓度。前列腺按摩、前列腺活检或TURP等医源性因素可使血清PSA明显上升。此外，经直肠B超检查、膀胱镜检查、尿潴留及细菌性前列腺炎症等因素亦可能会影响PSA的水平。上述除生理因素影响外，前列腺炎症可持续作用而影响前列腺腺体周围环境。那么，临床上所见血清PSA异常升高的BPH患者，是否为因同时有前列腺炎症影响所致呢?
鉴于对前列腺癌的诊断、鉴别诊断及治疗的要求，提高PSA作为其瘤标的敏感性和特异性，本课题对经病理证实的172例BPH患者前列腺标本切片进行分析研究，以期发现BPH患者血清PSA升高的原因，并探讨其发生机制。
研究目的：
本课题拟对经病理证实的172例BPH患者手术切除的前列腺组织标本切片分析研究，应用HE染色和免疫组化技术PSA染色，从而发现血清PSA升高的BPH患者前
列腺腺体的变化，以及PSA在前列腺的分泌和表达的改变，探讨其升高的病因和机制。
方法:
1、HE染色
切片于二甲苯中脱蜡，梯度酒精脱蜡水化，Lillie Maye:氏苏木素染色，1%盐酸
乙醇溶液分化，自来水冲洗，伊红染色;再用自来水冲洗，分色。梯度酒精脱水，石
碳酸二甲苯透明，中性树胶封片。
2、PSA染色
10%缓冲中性甲醛固定，常规脱水、透明、浸蜡、包埋，切片厚1.5一Zpm，二甲
苯中脱蜡，梯度酒精脱蜡水化，3%HZOZ处理，PBS冲洗;抗原修复，PBS冲洗;多
聚赖氨酸贴附，用PBS代替一抗作阴性对照。经微波炉92一98’C 10min进行处理，滴
加一抗和二抗，PBS冲洗;DAB显色，苏木素复染，常规脱水、透明、封片。
3、血清PSA检测
血清PSA采用放射免疫分析法，于术前晨6一7时采静脉血Zml(采血前均未服用
5。一还原酶抑制剂及其它内分泌药物，2周避免尿道内操作及直肠指检)，分离血清后
用进行检测，采用美国Beckman公司生产的全自动化学发光免疫仪及其相应试剂盒。
4、前列腺体积测定
经直肠B超测定前列腺上下径(DI)、前后径(DZ)和左右径(D3)，前列腺体积
(v)采用近似长椭球体公式v=二/6XD，只nZxo3(cm3)计算。
5、统计分析
172例患者按血清PsA值分3组:A组<4ng·ml一‘;B组)4一
胞。每组按HE染色、PSA染色标本见有无多灶性淋巴细胞浸润分为1组和2组。血
清PSA数据用SPSSH.O软件进行单因素方差分析和行x列x“检验分析，均数采用尤
士:表示，以尸<0.05为有显著性差异。
实验结果:
1、单纯间质性炎淋巴细胞浸润，如无腺上皮区的破坏，血清PSA在正常范围。
2、炎症或其他因素累及腺上皮可致血清PSA升高，前列腺腺体破坏程度愈大，
血清PSA升高愈明显。
3、血清PSA水平改变与是否合并慢性前列腺炎无相关性，炎症影响为非特异性。
4、血清PSA妻1ong’ ml-l者，免疫组化显示其前列腺间质以及血管中有染色的
PsA抗原，4ng·ml一，生血清PsA<10ng’ mr’者前列腺间质及血管偶可见PsA染色，
而血清PsA<4ng’ ml一’者则无。
结论:
1、支持“渗漏学说”:当BPH患者腺体受各种因素影响导致扩张、破坏时，PSA
渗漏入间质，继而进入血液循环，血清 PSA明显升高。
2、腺体破坏程度决定血清PSA升高程度。
Baekground:
Benign Prostatic hyPerplasia(BPH)15 a common disease in male more than 50 years
old，and eareinoma of Prostate(PCa)15 also easy to haPPen in the erowd.Therefore，early
diagnosis and differential diagnosis are imPortant significanee.From the 10 years reeently，
Prostate sPecfie antigen(PSA)in blood serum has already been the widest mark of PCa in
clinieal study and aPPlication，whieh have the sensibility and sPeeifieity for PCa screening
and whieh are eorresPonding elinieal value to judging PCa size，staging and grading，to
seleeting PCa treatment，to judging therapeutie effeet and to estimating and monitoring
Pfogn0SIS.
The serum PsA of the common ma一e 15 less than 4 ng·ml.l，whose diurual variation 15
tiny.BPH and PCa，5 serum PSA are rising，whose age with disease are in eonformity.Their
excreting PSA ways are also different，which make the serunn PSA level disParated.80
percents of Pea serum PsA in elinic are more出an 4 ng·ml’1.HowevertheserumPsAof
BPH Patients are lighely rising because of their gland ePithelial tissue hyPerblastosis and
volume augmentation Primarily exeePt for their ages，and the major are in normal range(<4
ng·ml’l).But the serum PsA ofthe partial ones are rising disparitly.Aeeording to Hudson;s
rePorts， there are about 2 or 3 Pereents of the Patienis that their serum PSA are more than
long·ml’1，whieh eouldn，t be enough to be explained only on the above一mentioned
Physiologie factor’5 Point of view.And now there are not eorrelated rePorts.
ExcePt the above一mentioned factors that are able to effect the serum PSA as yet，
androgen and ejaeulation also may effect the density of PSA.The iatrogenie factors，for
examPle，Prostatic massage，Prostate bioPsy and TURP，may make the serum PSA rise
obviously.In addition，the Per reetum tyPe一B ultrasonie，eystoscoPe eheek，uroschesis and
bacteral Prostatitis ete，maybe influence the lever of PSA.Among the above一mentioned
factors excePt for the Physiologic ones，Prostatitis can Persistently effect the environment of
Prostate gland.Then whether or not that 15 the reason of the serurn PSA rising that BPH
Patients are with Prostatitis?
In view of the requirement to diagnose，differential diagnosis and treatment of PCa，
raising the PSA’5 sensitivity and sPecifieity as the tumorous mark，the toPie analyzes and
studies the 1 72 BPH patients’prostate specimen sliees whieh have been verificated on
Pathology.Form this we hoPe that we ean find out the reason of the BPH Patienis’serum
PSA rising and investigate the meehanisms.
objeetives
The toPie will analyze and study the 1 72 BPH Patienis’Prostate exairesis sPeeimen
sliees whieh have been verifieated on Pathology，HE dyeing and PSA
immunohistoehemistry dyeing utilized.Then we ean find out the variation of BPH Patients’
Prostate gland when the serurn PSArising，and ehanges of PSA seeretion and exPression on
Prostate，from whieh we eould investigate the etioPathogenisis and the meehanisms.
Methods:
l、HE dyeing
Sliee deParaffinaged in xylol，hydrated in gradieni aleohol，dyeing in Lillie Mayer
hematoxylin staining solution，differentiated inl%liquor of hydroehlorie aeid and aleohol，
flushed with water，dyeing eosine staining solution，flushed with water again，seParating
eolor.gradieni aleoholie dehydrated，the mixed liquor of fenol and xylol eleared，neutral
gurn mounied.
2、PSA dyeing
10%buffering neutral formalin fixed;routine arthydration，elearing，immerse wax，
embedding;1 .5一2 p m slice stretehed，sliee deParaffinaged in xylol，hydrated in gradieni
alcohol，dealed with3%hydrogen Peroxide，rinsed with PBS，antlgen restored，rinsed with
PBS again，attached with Polylysine，negative eontrolled with PBS rePlaeed of monantigen.
Dealed with mierowave oven for 1 0 minutes in 92一98oC，monantigen and diPlantigen
droPwised，rinsed with PBS again，eolourated with DAB，afterstained with hematoxylin.
routine dePrivated，elearing，mounting.
二
3 the serum PSA detection
Detection with radio
引文
1. Wang MC, Papsidero LD ,Kuriyama M. Prostate antigen: a new potential marker for prostatic cancer. Prostate, 1981,2: 89-96.
2. Papsidero LD ,Wang MC ,Valenzuela LA. A prostate antigen in sera of prostatic cancer patients. Cancer-Res. 1980,40: 2428-32.
3. Papsidero LD ,Kuriyama M ,Wang MC. Prostate antigen: a marker for human prostate epithelial cells. J-Natl-Cancer-Inst. 1981,66: 37-42,
4. Kuriyama M ,Wang MC ,Papsidero LD. Quantitation of prostate-specific antigen in serum by a sensitive enzyme immunoassay. Cancer-Res. 1980,40: 4658-62.
5. Papsidero LD, Wojcieszyn JW ,Horoszewicz JS. Isolation of prostatic acid phosphatase-binding immunoglobulin G from human sera and its potential for use as a tumor-localizing reagent. Cancer-Res. 1980,40(8 Pt 2): 3032-5.
6. Glander HJ ,Kratzsch J ,Weisbrich C. Insulin-like growth factor-Ⅰ and alpha 2-macroglobulin in seminal plasma correlate with semen quality. Hum-Reprod. 1996 Nov; 11: 2454-60.
7. Peehl DM ,Cohen P ,Rosenfeld RG. The insulin-like growth factor system in the prostate.World-J-Urol. 1995,13: 306-11.
8. Fielder PJ ,Rosenfeld RG ,Graves HC . Biochemical analysis of prostate specific antigen-proteolyzed insulin-like growth factor binding protein-3. Growth-Regul. 1994,4: 164-72.
9. Clements J ,Mukhtar A. Glandular kallikreins and prostate-specific antigen are expressed in the human endometrium.J-Clin-Endocrinol-Metab. 1994,78: 1536-9.
10. Bjork T,Piironen T,Pettersson K. Comparison of analysis of the different prostate-specific antigen forms in serum for detection of clinically localized prostate cancer.Urology. 1996,48: 882-8.
11. Stenman UH ,Leinonen J ,Alfthan H. A complex between prostate-specific antigen and
alpha 1-antichymotrypsin is the major form of prostate-specific antigen in serum of patients with prostatic cancer: assay of the complex improves clinical sensitivity for cancer.Cancer-Res. 1991 ,51 : 222-6.
12. Naya Y ,Stamey TA ,Cheli CD. Can volume measurement of the prostate enhance the performance of complexed prostate-specific antigen?Urology. 2002 ,60(4 Suppl 1): 36-41.
13. Yamamoto M ,Hibi H ,Miyake K .Hinyokika-Kiyo. Prostate-specific antigen levels in acute and chronic bacterial prostatitis. 1993,39: 445-9.
14. Chybowski FM ,Bergstralh EJ ,Oesterling JE. The effect of digital rectal examination on the serum prostate specific antigen concentration: results of a randomized study.J Urol. 1992,148: 83-6.
15. Moon TD ,Clejan S ,Neal DE Jr . Prostate specific antigen and prostatitis. Ⅱ. PSA production and release kinetics in vitro. Prostate. 1992,20: 113-6.
16. Stamey TA ,Ekman PE ,Blankenstein MA. Tumor markers. Consensus Conference on Diagnosis and Prognostic Parameters in Localized Prostate Cancer. Stockholm, Sweden, May 12-13, 1993.Scand-J-Urol-Nephrol-Suppl. 1994,162: 73-87; discussion 115-27.
17. Herschman JD,Smith DS ,Catalona WJ. Effect of ejaculation on serum total and free prostate-specific antigen concentrations.Urology. 1997,50: 239-43.
18. Yuan JJ ,Coplen DE ,Petros JA . Effects of rectal examination, prostatic massage, ultrasonography and needle biopsy on serum prostate specific antigen levels.J-Urol. 1992,147(3 Pt 2): 810-4.
19. Bossens MM ,Van-Straalen JP ,De-Reijke TM. Kinetics of prostate-specific antigen after manipulation of the prostate.Eur-J-Cancer. 1995,31 A: 682-5.
20. Stamey TA ,Johnstone IM ,McNeal JE . Preoperative serum prostate specific antigen levels between 2 and 22 ng./ml, correlate poorly with post-radical prostatectomy cancer morphology: prostate specific antigen cure rates appear constant between 2 and 9 ng./ml.J-Urol. 2002,167: 103-11.
21. Oesterling JE ,Roy J ,Agha A. Biologic variability of prostate-specific antigen and its
usefulness as a marker tier prostate cancer: effects of tinasteride. The Finasteride PSA Study Group.Urology. 1997,50: 13-8.
22. Brawer MK ,Lin DW ,Williford WO. Effect of finasteride and/or terazosin on serum PSA: results of VA Cooperative Study #359.Prostate. 1999,39: 234-9.
23. Pansadoro V ,Emiliozzi P ,Defidio L. Prostate-specific antigen and prostatitis in men under fifty.Eur-Urol. 1996,30: 24-7.
24. Moon TD ,Clejan S ,Neal DE Jr . Prostate specific antigen and prostatitis. Ⅱ. PSA production and release kinetics in vitro.Prostate. 1992,20: 113-6.
25. Hasui Y ,Marutsuka K ,Asada Y. Relationship between serum prostate specific antigen and histological prostatitis in patients with benign prostatic hyperplasia.Prostate. 1994,25: 91-6.
26. Anim JT ,Udo C ,John B. Characterisation of inflammatory cells in benign prostatic hyperplasia.Acta-Histochem. 1998,100: 439-49.
27．夏同礼，孔祥田，宓培，等．我国成人前列腺非特异性炎．中华泌尿外科杂志．1995，16：711-712．
28. van Krieken JH. Am J Surg Pathol .Prostate marker immunoreactivity in salivary gland neoplasms. A rare pitfall in immunohistochemistry. 1993,17:410-414.
29. Yu H, Diamandis EP ,Sutherland DJ .Immunoreactive prostate-specific antigen levels in female and male breast tumors and its association with steroid hormone receptors and patient age .Clin Biochem. 1994,27:75-79.
30. Yu H ,Giai M ,Diamandis EP .Prostate-specific antigen is a new favorable prognostic indicator for women with breast cancer .Cancer Res. 1995,55:2104-2110.
31. Monne M ,Croce CM ,Yu H .Molecular characterization of prostate-specific antigen messenger RNA expressed in breast tumors .Cancer Res. 1994,54:6344-6347.
32. Clements JA ,The human kallikrein gene family: a diversity of expression and function .Mol Cell Endocrin. 1994,99:C 1-6.
33. Yu H ,Diamandis EP. Prostate-specific antigen in milk of lactating women .Clin Chem .1995,41:54-58.
34. Kirollos MM. Prostate-specific antigen and age ,is there a correlation ?And why does it seem to vary ?Eur Urol ,1996,30:296-301.
35. Collins GN ,Lee RJ ,Mckelivie GB .Relationship between prostate specific antigen prostate volume and age in the benign prostate .Br J Urol. 1993,71:445-450.
36. Wu B ,Itoh Y ,Saitoh M .The realationship between serum PSA value and the weight of the inner gland of the prostate in the cases of benign prostatic hyporplasiax .Nippon Hinyokika Gakai Easshi. 1995,86:1525.
37. Cevik I ,Turkeri LN ,Ozveri H .Short-term effect of digital rectal examination on serum prostate-specific antigen levels ,A prospextive study .Eur Urol. 1996,29:403-406.
38. Matzkin H ,Laufer M ,Chen J .Effect of eletive prolonged urethral catheterization on serum prostate-specific antigen concentration .Urology. 1996,48:63-66.
39. Crawford ED 3rd ,Mackenzie SH ,Safford HR .The effect of bicycle riding on serum prostate specific antigen levels.J Urol. 1996,156:103-105.
40. Yuan JJ ,Coplen DE ,Petros JA .Effects of rectal examination ,prostatic massage ,ultrasonography and needle biopsy on serum prostate specific antigen levels .J Urol. 1992,147:810-814.
41. Pansadoro V ,Emiliozzi P ,Defidi L .Prostate specific antigen and prostatitis in men undeerfifty .Eur Urol. 1996,30:24-27.
42．梅骅．前列腺癌的临床诊断[M]．见：郭应禄主编．前列腺增生及前列腺癌．北京：人民卫生出版社，1998．177．
43. Tchegen MB, Oesterling JE. The role of prostate-specific antigen in the evaluation of benign prostatic hyperplasia. Urol Clin North Am, 1995,22:333-336.
44. Stamey TA, Kabalin JN, Mcneal JE,et al.Prostate specific antigen in the diagnosis and treatment of adenocarcinoma of the prostate. Ⅱ Radical prostatectomy treated patients. J Urol,1989,141:1076-1083.
45. Kibel AS ,Krithivas K ,Shamel LB .Constitutive expression of high levels of prostate-specific antigen in the absence of prostate carcinoma. Urology. 1996, 48: 741-746.
46. Irani J, Levillain P, Geujon JM. Inflammation in benign prostatic hyperplasia: correlation with prostate specific antigen value .J Urol. 1997, 157, 1301-1303.
47. Yuan JJJ, Coplen DE, petros JA, et al. Effects of rectal examination , prostatic massage, ultrasonography and needle biopsy on serum prostate specific antigen levels. J Urol,1992,147:810-814.
48. Jung K ,Meyer A ,Lein M .Ratio of free-to-total prostate specific antigen in serum cannot distinguish patients with prostate cancer from those with chronic inflammation of the prostate .J Urol. 1998,159:1595-1598.
2. Papsidero LD ,Wang MC ,Valenzuela LA. A prostate antigen in sera of prostatic cancer patients. Cancer-Res. 1980,40: 2428-32.
3. Papsidero LD ,Kuriyama M ,Wang MC. Prostate antigen: a marker for human prostate epithelial cells. J-Natl-Cancer-Inst. 1981,66: 37-42,
4. Kuriyama M ,Wang MC ,Papsidero LD. Quantitation of prostate-specific antigen in serum by a sensitive enzyme immunoassay. Cancer-Res. 1980,40: 4658-62.
5. Papsidero LD, Wojcieszyn JW ,Horoszewicz JS. Isolation of prostatic acid phosphatase-binding immunoglobulin G from human sera and its potential for use as a tumor-localizing reagent. Cancer-Res. 1980,40(8 Pt 2): 3032-5.
6. Glander HJ ,Kratzsch J ,Weisbrich C. Insulin-like growth factor-Ⅰ and alpha 2-macroglobulin in seminal plasma correlate with semen quality. Hum-Reprod. 1996 Nov; 11: 2454-60.
7. Peehl DM ,Cohen P ,Rosenfeld RG. The insulin-like growth factor system in the prostate.World-J-Urol. 1995,13: 306-11.
8. Fielder PJ ,Rosenfeld RG ,Graves HC . Biochemical analysis of prostate specific antigen-proteolyzed insulin-like growth factor binding protein-3. Growth-Regul. 1994,4: 164-72.
9. Clements J ,Mukhtar A. Glandular kallikreins and prostate-specific antigen are expressed in the human endometrium.J-Clin-Endocrinol-Metab. 1994,78: 1536-9.
10. Bjork T,Piironen T,Pettersson K. Comparison of analysis of the different prostate-specific antigen forms in serum for detection of clinically localized prostate cancer.Urology. 1996,48: 882-8.
11. Stenman UH ,Leinonen J ,Alfthan H. A complex between prostate-specific antigen and
alpha 1-antichymotrypsin is the major form of prostate-specific antigen in serum of patients with prostatic cancer: assay of the complex improves clinical sensitivity for cancer.Cancer-Res. 1991 ,51 : 222-6.
12. Naya Y ,Stamey TA ,Cheli CD. Can volume measurement of the prostate enhance the performance of complexed prostate-specific antigen?Urology. 2002 ,60(4 Suppl 1): 36-41.
13. Yamamoto M ,Hibi H ,Miyake K .Hinyokika-Kiyo. Prostate-specific antigen levels in acute and chronic bacterial prostatitis. 1993,39: 445-9.
14. Chybowski FM ,Bergstralh EJ ,Oesterling JE. The effect of digital rectal examination on the serum prostate specific antigen concentration: results of a randomized study.J Urol. 1992,148: 83-6.
15. Moon TD ,Clejan S ,Neal DE Jr . Prostate specific antigen and prostatitis. Ⅱ. PSA production and release kinetics in vitro. Prostate. 1992,20: 113-6.
16. Stamey TA ,Ekman PE ,Blankenstein MA. Tumor markers. Consensus Conference on Diagnosis and Prognostic Parameters in Localized Prostate Cancer. Stockholm, Sweden, May 12-13, 1993.Scand-J-Urol-Nephrol-Suppl. 1994,162: 73-87; discussion 115-27.
17. Herschman JD,Smith DS ,Catalona WJ. Effect of ejaculation on serum total and free prostate-specific antigen concentrations.Urology. 1997,50: 239-43.
18. Yuan JJ ,Coplen DE ,Petros JA . Effects of rectal examination, prostatic massage, ultrasonography and needle biopsy on serum prostate specific antigen levels.J-Urol. 1992,147(3 Pt 2): 810-4.
19. Bossens MM ,Van-Straalen JP ,De-Reijke TM. Kinetics of prostate-specific antigen after manipulation of the prostate.Eur-J-Cancer. 1995,31 A: 682-5.
20. Stamey TA ,Johnstone IM ,McNeal JE . Preoperative serum prostate specific antigen levels between 2 and 22 ng./ml, correlate poorly with post-radical prostatectomy cancer morphology: prostate specific antigen cure rates appear constant between 2 and 9 ng./ml.J-Urol. 2002,167: 103-11.
21. Oesterling JE ,Roy J ,Agha A. Biologic variability of prostate-specific antigen and its
usefulness as a marker tier prostate cancer: effects of tinasteride. The Finasteride PSA Study Group.Urology. 1997,50: 13-8.
22. Brawer MK ,Lin DW ,Williford WO. Effect of finasteride and/or terazosin on serum PSA: results of VA Cooperative Study #359.Prostate. 1999,39: 234-9.
23. Pansadoro V ,Emiliozzi P ,Defidio L. Prostate-specific antigen and prostatitis in men under fifty.Eur-Urol. 1996,30: 24-7.
24. Moon TD ,Clejan S ,Neal DE Jr . Prostate specific antigen and prostatitis. Ⅱ. PSA production and release kinetics in vitro.Prostate. 1992,20: 113-6.
25. Hasui Y ,Marutsuka K ,Asada Y. Relationship between serum prostate specific antigen and histological prostatitis in patients with benign prostatic hyperplasia.Prostate. 1994,25: 91-6.
26. Anim JT ,Udo C ,John B. Characterisation of inflammatory cells in benign prostatic hyperplasia.Acta-Histochem. 1998,100: 439-49.
27．夏同礼，孔祥田，宓培，等．我国成人前列腺非特异性炎．中华泌尿外科杂志．1995，16：711-712．
28. van Krieken JH. Am J Surg Pathol .Prostate marker immunoreactivity in salivary gland neoplasms. A rare pitfall in immunohistochemistry. 1993,17:410-414.
29. Yu H, Diamandis EP ,Sutherland DJ .Immunoreactive prostate-specific antigen levels in female and male breast tumors and its association with steroid hormone receptors and patient age .Clin Biochem. 1994,27:75-79.
30. Yu H ,Giai M ,Diamandis EP .Prostate-specific antigen is a new favorable prognostic indicator for women with breast cancer .Cancer Res. 1995,55:2104-2110.
31. Monne M ,Croce CM ,Yu H .Molecular characterization of prostate-specific antigen messenger RNA expressed in breast tumors .Cancer Res. 1994,54:6344-6347.
32. Clements JA ,The human kallikrein gene family: a diversity of expression and function .Mol Cell Endocrin. 1994,99:C 1-6.
33. Yu H ,Diamandis EP. Prostate-specific antigen in milk of lactating women .Clin Chem .1995,41:54-58.
34. Kirollos MM. Prostate-specific antigen and age ,is there a correlation ?And why does it seem to vary ?Eur Urol ,1996,30:296-301.
35. Collins GN ,Lee RJ ,Mckelivie GB .Relationship between prostate specific antigen prostate volume and age in the benign prostate .Br J Urol. 1993,71:445-450.
36. Wu B ,Itoh Y ,Saitoh M .The realationship between serum PSA value and the weight of the inner gland of the prostate in the cases of benign prostatic hyporplasiax .Nippon Hinyokika Gakai Easshi. 1995,86:1525.
37. Cevik I ,Turkeri LN ,Ozveri H .Short-term effect of digital rectal examination on serum prostate-specific antigen levels ,A prospextive study .Eur Urol. 1996,29:403-406.
38. Matzkin H ,Laufer M ,Chen J .Effect of eletive prolonged urethral catheterization on serum prostate-specific antigen concentration .Urology. 1996,48:63-66.
39. Crawford ED 3rd ,Mackenzie SH ,Safford HR .The effect of bicycle riding on serum prostate specific antigen levels.J Urol. 1996,156:103-105.
40. Yuan JJ ,Coplen DE ,Petros JA .Effects of rectal examination ,prostatic massage ,ultrasonography and needle biopsy on serum prostate specific antigen levels .J Urol. 1992,147:810-814.
41. Pansadoro V ,Emiliozzi P ,Defidi L .Prostate specific antigen and prostatitis in men undeerfifty .Eur Urol. 1996,30:24-27.
42．梅骅．前列腺癌的临床诊断[M]．见：郭应禄主编．前列腺增生及前列腺癌．北京：人民卫生出版社，1998．177．
43. Tchegen MB, Oesterling JE. The role of prostate-specific antigen in the evaluation of benign prostatic hyperplasia. Urol Clin North Am, 1995,22:333-336.
44. Stamey TA, Kabalin JN, Mcneal JE,et al.Prostate specific antigen in the diagnosis and treatment of adenocarcinoma of the prostate. Ⅱ Radical prostatectomy treated patients. J Urol,1989,141:1076-1083.
45. Kibel AS ,Krithivas K ,Shamel LB .Constitutive expression of high levels of prostate-specific antigen in the absence of prostate carcinoma. Urology. 1996, 48: 741-746.
46. Irani J, Levillain P, Geujon JM. Inflammation in benign prostatic hyperplasia: correlation with prostate specific antigen value .J Urol. 1997, 157, 1301-1303.
47. Yuan JJJ, Coplen DE, petros JA, et al. Effects of rectal examination , prostatic massage, ultrasonography and needle biopsy on serum prostate specific antigen levels. J Urol,1992,147:810-814.
48. Jung K ,Meyer A ,Lein M .Ratio of free-to-total prostate specific antigen in serum cannot distinguish patients with prostate cancer from those with chronic inflammation of the prostate .J Urol. 1998,159:1595-1598.