2022年世界卫生组织（WHO）分类不再推荐乳头状肾细胞癌（PRCC）组织学亚型分型。目前，WHO/ISUP核仁分级是PRCC的唯一接受的预后组织学参数。在PRCC中，ABCC2(一种肾脏药物转运蛋白)已被证明能显著预测结果。在这项研究中，我们评估了大型多机构PRCC队列中ABCC2免疫组织化学（IHC）染色模式的预后意义，并评估了这些模式与ABCC2 mRNA表达的关联。我们对254例PRCC进行了ABCC2 IHC反应模式评估，并分为阴性、细胞质、刷状缘＜50%和刷状缘≥50%。我们采用RNA原位杂交（ISH）来确定每组转录水平。我们使用SPSS和GraphPad软件进行生存分析。RNA-ISH显示，与阴性/细胞质组相比，任何刷状缘染色的ABCC2组与显著增加的转录水平相关（P=0.034）。在单变量分析中，刷状缘＜50%（P=0.024）和刷状缘≥50%（P<0.001）的ABCC2组也与更差的无病生存期（DFS）相关。多变量分析显示，只有ABCC2 IHC刷状缘（<50%和≥50%）反应组（分别为P=0.037和P=0.003），以及高期疾病（P<0.001）具有预后意义的DFS。此外，ABCC2刷状缘在pT1a（P=0.014）、pT1（P=0.013）、≤4cm肿瘤（P=0.041）和高期（P=0.014）组中显示出显著较差的DFS，而这些组中高WHO/ISUP分级的类似分析不显著。ABCC2 IHC刷状缘在PRCC中与显著较高的基因表达相关，并且独立预测生存结果。© 2023 The Authors. John Wiley＆Sons Ltd.发表的组织病理学。

Papillary renal cell carcinoma (PRCC) histologic subtyping is no longer recommended in the 2022 WHO classification. Currently, WHO/ISUP nucleolar grade is the only accepted prognostic histologic parameter for PRCC. ABCC2, a renal drug transporter, has been shown to significantly predict outcomes in PRCC. In this study we evaluated the prognostic significance of ABCC2 IHC staining patterns in a large, multi-institutional PRCC cohort and assessed the association of these patterns with ABCC2 mRNA expression.We assessed 254 PRCCs for ABCC2 IHC reactivity patterns that were stratified into negative, cytoplasmic, brush-border <50%, and brush-border ≥50%. RNA in situ hybridization (ISH) was used to determine the transcript level of each group. Survival analysis was performed with SPSS and GraphPad software. RNA-ISH showed that the ABCC2 group with any brush-border staining was associated with a significant increase in the transcript level, when compared to the negative/cytoplasmic group (P = 0.034). Both ABCC2 groups with brush-border <50% (P = 0.024) and brush-border ≥50% (P < 0.001) were also associated with worse disease-free survival (DFS) in univariate analysis. Multivariate analysis showed that only ABCC2 IHC brush-border (<50% and ≥50%) reactivity groups (P = 0.037 and P = 0.003, respectively), and high-stage disease (P < 0.001) had a DFS of prognostic significance. In addition, ABCC2 brush-border showed significantly worse DFS in pT1a (P = 0.014), pT1 (P = 0.013), ≤4 cm tumour (P = 0.041) and high stage (P = 0.014) groups, while a similar analysis with high WHO/ISUP grade in these groups was not significant.ABCC2 IHC brush-border expression in PRCC correlates with significantly higher gene expression and also independently predicts survival outcomes.© 2023 The Authors. Histopathology published by John Wiley & Sons Ltd.