Etiology of Development of BPH and the mechanism of Hormon-Refractory prostate cancer in the Human Prostate

人类前列腺中 BPH 发生的病因学和激素难治性前列腺癌的机制

• 批准号: 12671524
• 负责人: KATO Haruaki
• 金额: $ 2.11万
• 依托单位: Shinshu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671524/
• 关键词: Prostate; Benign prostatic; Hormon-Refractory Prostate Cancer; neuroendocrine cell; paraurethral gland; Female diverticular cancer; Mullerin duet remnant; 傍尿道腺

The distribution of neuroendocaine ( NE ) cells in human prostate showed a decrease in density in the peripheral acini and an increase in the main prostatic ductal systems. In BPH, the NE cells are completely absent in its acini. Thus the NE cells are not related to the prostate growth and the generally accepted stem cell theory can not be adapted to the development of BPH. Furthermore, basal cells may lose the ability to differentiate into the NE cells in the BPH from the study ofPSA and Keratin 34 beta E 12. Another important finding we observed is that the focal atrophic glands mimicking cancer tissue are mainly consist of the basal cell layer with no positive PSA staining. We tried to stain various nerve fibers in relation to development of BPH. However, we could not find any relationship between their distribution and zonal anatomy of the human prostate at present. We successfully classified the Mullerian remnant diseases by the accumulated knowledge of immunohistochemical study o … More f the utricle. The results of immunohistochemical study of cathepsin D showed that expression of cathepsin D granules was intense in the proximal ducts while it was weak or absent in the peripheral acini in normal adult prostate. Conversely, strong expression of the granules was observed in the peripheral acini and its expression wasmarkedly reduced in the proximal ducts after androgen ablation. In the cases of ductal prostatic cancer, carcinoembryonic antigen ( CEA ) positive nests observed. This suggests the ductal part of the prostate can be differentiated into CEA positive cancer. We investigated six cases of female urethral diverticular adenocarcinoma, which was presumed to originate from the paraurethral gland ( homologous to male prostate gland ). All mucous producing cancer showed positivity of CEA and 2 of them showed neuroendocrine differentiation. In view of nomal histology of female paraurethral gland, these findings suggested that the mucous secreting adenocarcinoma might originate from the proximal part of the ducts. Less

人前列腺中神经内卡因 (NE) 细胞的分布显示，周围腺泡密度降低，而主前列腺导管系统密度增加。在 BPH 中，腺泡中完全不存在 NE 细胞。因此NE细胞与前列腺生长无关，普遍接受的干细胞理论不能适应BPH的发展。此外，从PSA和角蛋白34βE 12的研究来看，BPH中基底细胞可能失去分化为NE细胞的能力。我们观察到的另一个重要发现是，模仿癌组织的局灶性萎缩腺体主要由没有PSA阳性染色的基底细胞层组成。我们尝试对与 BPH 发展相关的各种神经纤维进行染色。然而，目前我们还没有发现它们的分布与人类前列腺的带状解剖之间的任何关系。通过对椭圆囊的免疫组织化学研究积累的知识，我们成功地对苗勒氏管残余疾病进行了分类。组织蛋白酶D免疫组化研究结果显示，正常成人前列腺组织蛋白酶D颗粒在近端导管中表达强烈，而在周围腺泡中表达较弱或不表达。相反，在雄激素消融后，在外周腺泡中观察到颗粒的强烈表达，并且在近端导管中其表达显着减少。在导管前列腺癌病例中，观察到癌胚抗原（CEA）阳性巢。这表明前列腺导管部分可以分化为 CEA 阳性癌症。我们调查了六例女性尿道憩室腺癌，推测其起源于尿道旁腺（与男性前列腺同源）。所有产生粘液的癌症均显示 CEA 阳性，其中 2 个显示神经内分泌分化。鉴于女性尿道旁腺的正常组织学，这些结果提示分泌粘液的腺癌可能起源于尿道旁腺的近端部分。较少的

项目成果

Ogihara S, Kato H: "Endocrine cell distribution and expression of tissue-associated antigens in human female parauietinal duct"Int.J.Urol. 7. 10-15 (2000)

Ogihara S、Kato H：“人类女性子宫旁管中内分泌细胞的分布和组织相关抗原的表达”Int.J.Urol。

Islam M., Kato H., et al.: "Adenocarcinoma of female parauretinal duct showing neuroendocrine differentiation"Urology. 58. 1058iv-1058vi (2001)

Islam M.、Kato H. 等人：“显示神经内分泌分化的女性尿管旁管腺癌”泌尿学。

Kato,H. et al: "Histopathological study of the mullerian duct remnant: clarification of desease categories and terminology"J. Urol. 167. 133-136 (2002)

加藤，H.

Ogihara S, Kato H: "Endocrine cell distribution and expression of tissue-associated antigens in human female paraurethral duct"Int. J. Urol. 7. 10-15 (2000)

Ogihara S、Kato H：“人类女性尿道旁管中内分泌细胞的分布和组织相关抗原的表达”Int。

Islam M, Kato H et al.: "Adenocarcinoma of female para meteral duct showing neuroendocrine differentiation"Urology. 58. 1058iv-1058vi (2001)

Islam M、Kato H 等人：“显示神经内分泌分化的女性子宫旁管腺癌”泌尿外科。