Bostwick D G, Pacelli A, Lopez-Beltran A
Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Prostate. 1996 Aug;29(2):117-34. doi: 10.1002/(SICI)1097-0045(199608)29:2<117::AID-PROS7>3.0.CO;2-C.
High-grade PIN is the most likely precursor of prostatic adenocarcinoma, according to virtually all available evidence to date. The clinical importance of recognizing PIN is based on its strong association with prostatic carcinoma. PIN has a high predictive value as a marker for adenocarcinoma. Its identification in biopsy specimens of the prostate warrants further search for concurrent invasive carcinoma. PIN is associated with progressive abnormalities of phenotype and genotype intermediate between normal prostatic epithelium and cancer, indicating impairment of cell differentiation and regulatory control with advancing stages of prostatic carcinogenesis. There is progressive gain or loss of a wide variety of biomarkers, including morphometric markers, differentiation markers, stromal markers, growth factors and associated receptors, oncogenes, tumor suppressor genes, and chromosomes. Abnormalities in expression of most biomarkers are amplified in the progression from high-grade PIN to localized cancer, metastatic cancer, and hormone-refractory cancer. Oncogenesis of prostatic carcinoma probably occurs through the selection of several genetic changes, each modifying the expression or function of genes controlling cell growth and differentiation. Further studies are needed to evaluate the function and prognostic value of oncogene expression in the normal, preneoplastic, and neoplastic prostate.
根据目前所有可得证据，高级别前列腺上皮内瘤变（PIN）很可能是前列腺腺癌的前驱病变。认识PIN的临床重要性基于其与前列腺癌的紧密关联。PIN作为腺癌的标志物具有较高的预测价值。在前列腺活检标本中发现PIN，就需要进一步查找是否同时存在浸润性癌。PIN与正常前列腺上皮和癌症之间表型及基因型的渐进性异常有关，这表明随着前列腺癌发生进程的推进，细胞分化和调控受到损害。包括形态学标志物、分化标志物、基质标志物、生长因子及其相关受体、癌基因、肿瘤抑制基因和染色体在内的多种生物标志物会出现渐进性增减。在从高级别PIN进展为局限性癌、转移性癌和激素难治性癌的过程中，大多数生物标志物表达的异常情况会加剧。前列腺癌的发生可能是通过选择多种基因变化实现的，每种变化都会改变控制细胞生长和分化的基因的表达或功能。需要进一步研究来评估癌基因表达在正常、癌前和肿瘤性前列腺组织中的功能及预后价值。
