摘要
研究晚期前列腺癌（Pca）组织中癌基质表达及变化，与去势治疗抵抗的（CRPC）的临床相关性。148例晚期Pca患者接受药物或手术去势，治疗后48个月设为临床随访终结时间，记录患者是否出现CRPC及时间。采用Massontrichrome染色法和vimentin、desmin免疫组化法检测癌基质中癌相关成纤维细胞（CAFs）的表达及分布特征。评估CRPC与CAFs分布、vimentin和desmin表达的相关性。结果发现，CAFs分布与Gleason评分存在负相关性。在Gleason6—7分Pca中，癌巢内CAFs分布（Masson82．8％VS45．6％，P〈0．001）、vimentin表达（P=0．005）显著高于临近癌旁组织，desmin表达显著减少（P=0．004）。在Gleason8—9分PCa中，癌巢内CAFs分布显著减少（Masson15％VS82．8％，P〈0．001）。生存率曲线分析显示在Gleason6-7分中，癌巢内CAFs分布与CRPC存在相关性（P=0．009），vimentin高表达者或desrnin低表达者，患者发生CRPC时间早，预后不佳；多因素变量分析显示癌巢内vimentin表达可作为PCa患者去势治疗后独立的预后指标（P=0．012）。结果表明PCa基质变化与CRPC存在相关性。对于Gleason6—7分且癌基质中CAFs高表达者，检测vimentin有助于发现易发生去势抵抗的PCa患者，可作为新的预后判断指标。
Reactive stromal changes in prostate cancer （PCa） are likely involved in the emergence of castration-resistant PCa （CRPC）. This study was designed to investigate stromal changes in patients with clinically advanced PCa and analyze their prognostic significance. Prostate needle biopsies obtained from 148 patients before castration therapy were analyzed by Masson trichrome staining and immunohistochemical analysis of vimentin and desmin. Reactive stroma grading was inversely correlated with Gleason score. Stroma grade （Masson stain 82.8% vs 45.6%, P 〈 0.001） and vimentin expression （P = 0.005） were significantly higher, and desmin expression （P = 0.004） significantly lower, in reactive stroma of tumors with a Gleason score of 6-7 than in adjacent peritumoral tissue. Kaplan-Meier analysis showed a significant association between reactive stroma grade in tumors and the occurrence of CRPC in patients with a Gleason score of 6-7 （P= 0.009）. Furthermore, patients with higher vimentin or lower desmin expression had a shorter disease-free period. In multivariate analysis, only vimentin expression was a significant predictor of tumor relapse （hazard ratio 1.78, 95% confidence interval 1.12-10.26, P = 0.012）. These findings indicate that the intensity of reactive stroma is associated with castration responsiveness, especially in patients with a lower Gleason score where the abundant stroma component is most frequently found. High expression of vimentin in tumor stroma was independently associated with poor outcomes in patients with Gleason scores of 6-7, and may serve as a new prognostic marker in daily practice.
