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肾损伤分子-1在病理T1b期透明细胞肾细胞癌中的表达:一种高免疫炎症状态和复发的潜在生物标志物

Kidney Injury Molecule-1 Expression in Pathological T1b Clear Cell Renal Cell Carcinoma: A Putative Biomarker of High Immune-Inflamed Status and Recurrence.

作者信息

Sugai Ayuna, Miyai Kosuke, Ito Keiichi, Matsukuma Susumu, Sato Kimiya

机构信息

Department of Basic Pathology, National Defense Medical College, Tokorozawa, Japan.

Department of Laboratory Medicine, National Defense Medical College Hospital, National Defense Medical College, Tokorozawa, Japan.

出版信息

Pathol Int. 2025 Jul;75(7):340-348. doi: 10.1111/pin.70024. Epub 2025 May 14.

Abstract

Kidney injury molecule-1 (KIM-1) is a potential prognostic marker of advanced-stage clear cell renal cell carcinoma (ccRCC) and is associated with tumor immunogenicity. Little is known about its role in early-stage ccRCC, especially in pathological T1b (pT1b) disease, which shows a higher recurrence rate than pT1a disease. Resected specimens from 112 pT1b ccRCC cases were reviewed and immunohistochemically analyzed for KIM-1 expression. High membranous KIM-1 expression was defined as H score ≥ 140, based on the immunoreactive intensity and area, and cytoplasmic expression in ≥ 10% of cancer cells was considered as high cytoplasmic KIM-1 expression. KIM-1 expression status was compared with clinicopathological variables, including tumor-associated immune cell (TAIC) status. Among the 112 cases, high membranous and cytoplasmic KIM-1 expression was observed in 30 (27%) and 38 (34%) cases, respectively. High membranous KIM-1 expression was significantly associated with a higher nuclear grade, tumor necrosis, hot TAIC status, and shorter recurrence-free survival (RFS) and cancer-specific survival, whereas high cytoplasmic expression was only related to a higher nuclear grade. Multivariate Cox regression analysis revealed that high membranous KIM-1 expression and tumor necrosis were independent predictors of shorter RFS. Our results indicate that membranous KIM-1 expression could be a biomarker for predicting postnephrectomy recurrence in pT1b ccRCC.

摘要

肾损伤分子-1(KIM-1)是晚期透明细胞肾细胞癌(ccRCC)的一种潜在预后标志物,且与肿瘤免疫原性相关。目前对其在早期ccRCC中的作用知之甚少,尤其是在病理T1b(pT1b)疾病中,该疾病的复发率高于pT1a疾病。回顾了112例pT1b ccRCC病例的切除标本,并对KIM-1表达进行了免疫组织化学分析。基于免疫反应强度和面积,高膜性KIM-1表达定义为H评分≥140,且≥10%的癌细胞中的细胞质表达被视为高细胞质KIM-1表达。将KIM-1表达状态与临床病理变量进行比较,包括肿瘤相关免疫细胞(TAIC)状态。在这112例病例中,分别在30例(27%)和38例(34%)中观察到高膜性和高细胞质KIM-1表达。高膜性KIM-1表达与更高的核分级、肿瘤坏死、活跃TAIC状态以及更短的无复发生存期(RFS)和癌症特异性生存期显著相关,而高细胞质表达仅与更高的核分级有关。多变量Cox回归分析显示,高膜性KIM-1表达和肿瘤坏死是RFS缩短的独立预测因素。我们的结果表明,膜性KIM-1表达可能是预测pT1b ccRCC肾切除术后复发的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c46/12288442/228c2793af13/PIN-75-340-g004.jpg

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