ERG和SPINK1蛋白在前列腺癌中表达的相互排斥性及其与预后的相关性

Prognostic significance of mutually exclusive expression of ERG and SPINK1 in endocrine-treated prostatic cancer

目的探讨ERG及SPINKl蛋白在前列腺癌中的表达及其与预后的相关性。方法选取进行内分泌治疗的前列腺癌穿刺标本118例，应用免疫组织化学EnVision法检测ERG及SPINKl蛋白在前列腺癌及正常前列腺组织中的表达情况，分析两者的表达与临床病理特征及预后之间的关系。结果118例前列腺癌活检标本中11例ERG蛋白表达阳性（11／118，9．3％），SPINKl蛋白在13例前列腺癌穿刺标本中表达阳性（13／118，11．0％）。未发现同时表达两种蛋白的病例。ERG阳性的患者具有较低的T分期（P=0．001），而患者的发病年龄、血清总前列腺特异性抗原（PSA）值、Gleason评分、肿瘤范围、远处转移等与ERG的表达均无相关性。SPINKl的表达与上述各项参数也无相关性。7例SPINKl阳性的患者（7／13）在治疗过程中出现了远处转移或者肿瘤相关性的死亡，相对于阴性的病例，具有较短的疾病进展时间（P=0．022）。根据ERG和SPINKl蛋白的表达情况将患者分为ERG’／SPINKl-、ERG-／SPINKl’以及ERG-／SPINKl—3组，分析其与疾病进展的相关性，显示3组之间差异有统计学意义，ERG一／SPINKl’组的患者与疾病进展具有显著相关性（P=0．029）。结论SPINKl和ERG蛋白的表达具有相互排斥性。前列腺癌中SPINKl蛋白的阳性表达与疾病进展之间存在明确相关性，可以作为判断患者预后的一个指标。

Objective To study the expression and prognostic significance of ERG and SPINK1 expression in endocrine-treated prostatic cancer. Methods Prostatic needle biopsies from 118 prostatic cancer patients primarily treated with endocrine therapy were reviewed. Immunohistochemical study for ERG and SPINK1 protein was carried out. Results Co-expression of ERG and SPINK1 was not observed. The frequency of ERG protein expression in the 118 biopsies studied was 9. 3% （11/118）. The positive expression correlated with T stage （ P = 0.04） but not with patient age at diagnosis, prostatic specific antigen level, Gleason＇s score, M stage, tumor area and progression-free survival. Positive expression of SPINK1 was demonstrated in 11.0% （ 13/118 ） of the biopsies. SPINKl-positive eases carried a significantly shorter progression-free survival, as compared with SPINKl-negative cases （ P = 0. 022 ）. The expression was not associated with any other clinicopathologie variables. The following expression pattern showed statistically significant correlation with the clinical progress （P =0. 029） ： ERG＋/SPINK1 - （11/118, 9.3% ）, ERG-/ SPINK1 ＋ （13/118, 11.0% ） and ERG-/SPINK1 - （94/118, 79. 7% ）. Conclusions ERG and SPINK1 proteins are mutually exclusive. SPINK1 expression is associated with more aggressive clinical behavior and can serve as a prognostic biomarker in prostatic cancer.