Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, United States of America.
Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, United States of America.
Exp Mol Pathol. 2020 Jun;114:104400. doi: 10.1016/j.yexmp.2020.104400. Epub 2020 Feb 12.
The morphology of Gleason 4 prostate cancer (PCa) can be subdivided into cribriform and non-cribriform patterns. A large body of evidence has shown that pattern 4 cribriform PCa (especially non-glomeruloid type) is associated with adverse pathologic features and clinical outcomes compared with non-cribriform pattern 4 PCa. The underlying mechanisms for the aggressiveness of cribriform PCa are not fully understood. The aim of this study is to compare the immunohistochemical expression of various biomarkers and to determine the potential proteins that may account for their biologic and clinical differences. A total of 14 biomarkers were studied. The number of non-glomeruloid cribriform PCa cases studied for each biomarker ranged from 18 to 74 and the number of non-cribriform pattern 4 PCa studied for each biomarker ranged from 29 to 112. We demonstrated that, compared with non-cribriform Gleason pattern 4 PCa, EGFR was significantly upregulated and standard CD44 (CD44s) was significantly downregulated in cribriform PCa; no significant differences were found in the expression of AR, NKX3.1, ERG, EZH2, p53, Rb, C-Myc, BCL2, p16, CyclinD1, Her2/Neu, and Synaptophysin between these two groups of pattern 4 PCa. The study also showed, compared to non-cribriform PCa, cribriform PCa presented with significantly higher serum PSA and more advanced tumor stage. The significant overexpression of EGFR and downregulation of CD44s in non-glomeruloid cribriform PCa may, at least, partly explain the unfavorable pathology and clinical results for this growth pattern. Given that EGFR targeted inhibitors are now available, the findings may also have significant therapeutic implications.
格里森 4 级前列腺癌（PCa）的形态可以细分为筛状和非筛状模式。大量证据表明，与非筛状 4 级 PCa 相比，模式 4 筛状 PCa（尤其是非肾小球样型）与不良病理特征和临床结局相关。筛状 PCa 侵袭性的潜在机制尚未完全阐明。本研究旨在比较各种生物标志物的免疫组化表达，并确定可能导致其生物学和临床差异的潜在蛋白。共研究了 14 种生物标志物。每种生物标志物研究的非肾小球样筛状 PCa 病例数为 18-74 例，每种生物标志物研究的非筛状 4 级 PCa 病例数为 29-112 例。我们表明，与非筛状格里森 4 级 PCa 相比，EGFR 在筛状 PCa 中显著上调，标准 CD44（CD44s）显著下调；在 AR、NKX3.1、ERG、EZH2、p53、Rb、C-Myc、BCL2、p16、CyclinD1、Her2/Neu 和突触素的表达方面，两组 4 级 PCa 之间无显著差异。该研究还表明，与非筛状 PCa 相比，筛状 PCa 的血清 PSA 水平更高，肿瘤分期更晚。非肾小球样筛状 PCa 中 EGFR 的显著过表达和 CD44s 的下调，至少部分解释了这种生长模式的不良病理和临床结果。鉴于现在已有 EGFR 靶向抑制剂，这些发现也可能具有重要的治疗意义。
