Foster C S, Bostwick D G, Bonkhoff H, Damber J E, van der Kwast T, Montironi R, Sakr W A
Department of Pathology, Liverpool University, UK.
Scand J Urol Nephrol Suppl. 2000(205):19-43. doi: 10.1080/003655900750169284.
Prostate cancer is usually heterogeneous and multifocal, with diverse clinical and morphologic manifestations. Current understanding of the molecular basis for this heterogeneity is limited, particularly for prostatic intraepithelial neoplasia (PIN), the only putative precursor which can be identified according to morphologic criteria. However, it is likely that prostatic adenocarcinoma might arise from precursor lesions other than PIN, although these cannot be recognized with certainty at the present time. In this review, we summarize the current state of knowledge regarding the cell-biological and genetic bases for linking PIN and prostatic adenocarcinoma. It is conceivable that a stem cell of basal phenotype, or an amplifying cell, is the target of prostatic carcinogenesis. Prominent genetic heterogeneity is characteristic of both PIN and carcinoma; and multiple foci of PIN arise independently within the same prostate. This observation suggests that a field effect probably underlies prostatic neoplasia. Multiple foci of cancer also often arise independently, lending additional support to this hypothesis. The strong genetic similarities between PIN and cancer strongly suggest that evolution and clonal expansion of PIN, or other precursor lesions, may account for the multifocal etiology of carcinoma. Uncertainties with respect to identification of those precursor lesions which are most likely to progress to invasive and metastatic prostate cancer reinforce the requirement for objective immunohistochemical or molecular biological markers of the aggressive phenotype.
前列腺癌通常具有异质性且多灶性，有着多样的临床和形态学表现。目前对这种异质性的分子基础的理解有限，尤其是对于前列腺上皮内瘤变（PIN）而言，它是唯一可根据形态学标准识别的假定前体病变。然而，前列腺腺癌可能起源于PIN以外的前体病变，尽管目前尚不能确切识别这些病变。在本综述中，我们总结了关于将PIN与前列腺腺癌联系起来的细胞生物学和遗传基础的当前知识状态。可以想象，具有基底表型的干细胞或扩增细胞是前列腺癌发生的靶点。显著的遗传异质性是PIN和癌的特征；并且PIN的多个病灶在同一前列腺内独立出现。这一观察结果表明，一种场效应可能是前列腺肿瘤形成的基础。多个癌灶也常常独立出现，为这一假说提供了更多支持。PIN和癌之间强大的遗传相似性强烈表明，PIN或其他前体病变的演变和克隆性扩增可能解释了癌的多灶性病因。对于那些最有可能进展为侵袭性和转移性前列腺癌的前体病变的识别存在不确定性，这强化了对侵袭性表型的客观免疫组化或分子生物学标志物的需求。
