Lee Jennifer, Yu Xiuping, Yeh Yunshin A
Pathology and Laboratory Medicine Service, Overton Brooks VA Medical Center Shreveport, LA 71101, USA.
Department of Pathology and Translational Pathobiology, Louisiana State University Health Shreveport Shreveport, LA 71103, USA.
Am J Clin Exp Urol. 2025 Aug 15;13(4):284-293. doi: 10.62347/EGWC8899. eCollection 2025.
Clear cell and papillary renal cell carcinomas (RCC) are the two most common RCC subtypes, accounting for approximately 70% and 15% of kidney cancers, respectively. Clear cell RCC is commonly associated with alterations, while papillary RCC typically exhibits chromosomal abnormalities such as +7, +17, and -Y. Furthermore, clear cell RCCs are less likely to exhibit and alterations. This study aims to improve the accuracy of RCC diagnosis by investigating molecular alterations in RCC cases with clear cells, papillary structures, and other atypical histological features.
Nine RCC cases were retrospectively selected and analyzed using histologic slides and immunohistochemical staining for CAIX, RCC, CD10, CK7, P504S, Vimentin, and EMA. Next-generation sequencing was performed on all cases to identify genetic mutations, and cytogenetic analysis was conducted on one case.
The cohort consisted of nine male patients aged 49 to 68 years (mean 61.4). Surgical specimens included six radical and three partial nephrectomies; seven tumors were located in the left kidney and two in the right. Tumor sizes ranged from 0.8 to 15.2 cm. Immunohistochemical analysis revealed positive staining for RCC (6/9), CAIX (3/4), CD10 (6/6), and CK7 (5/9). In six clear cell RCCs, next-generation sequencing identified mutations in four tumors, alterations in three, and mutations in one. Five tumors with papillary fronds, sarcomatous components, or unclassified features harboring , , and/or mutations were reclassified as clear cell RCC. One clear cell RCC with leiomyomatous stroma showed mutations. A case of clear cell papillary renal cell neoplasm showed no reportable gene mutations. The role of a mutation in one papillary RCC remains uncertain. Cytogenetic analysis of one case (Case #5) revealed 50, X, -Y, +3, +7, +16, +17, +20, consistent with papillary RCC.
Next-generation sequencing is a useful method for categorizing RCCs with clear cells, papillary features, and unusual histology. Additionally, mutations could be a promising target for personalized treatment in clear cell RCCs and their histologic variants.
透明细胞肾细胞癌和乳头状肾细胞癌（RCC）是两种最常见的RCC亚型，分别占肾癌的约70%和15%。透明细胞RCC通常与某些改变相关，而乳头状RCC通常表现出染色体异常，如+7、+17和-Y。此外，透明细胞RCC较少表现出某些改变。本研究旨在通过调查具有透明细胞、乳头状结构和其他非典型组织学特征的RCC病例中的分子改变，提高RCC诊断的准确性。
回顾性选择9例RCC病例，使用组织学切片以及针对CAIX、RCC、CD10、CK7、P504S、波形蛋白和EMA的免疫组织化学染色进行分析。对所有病例进行二代测序以鉴定基因突变，并对1例病例进行细胞遗传学分析。
该队列包括9名年龄在49至68岁之间的男性患者（平均61.4岁）。手术标本包括6例根治性肾切除术和3例部分肾切除术；7个肿瘤位于左肾，2个位于右肾。肿瘤大小范围为0.8至15.2厘米。免疫组织化学分析显示RCC（6/9）、CAIX（3/4）、CD10（6/6）和CK7（5/9）呈阳性染色。在6例透明细胞RCC中，二代测序在4个肿瘤中鉴定到某些基因突变，3个肿瘤中有某些改变，1个肿瘤中有某些基因突变。5个具有乳头状叶、肉瘤样成分或具有某些基因突变的未分类特征的肿瘤被重新分类为透明细胞RCC。1例具有平滑肌瘤样间质的透明细胞RCC显示出某些基因突变。1例透明细胞乳头状肾细胞肿瘤未显示可报告的基因突变。1例乳头状RCC中某基因突变的作用仍不确定。对1例病例（病例#5）的细胞遗传学分析显示50,X,-Y,+3,+7,+16,+17,+20，符合乳头状RCC。
二代测序是对具有透明细胞、乳头状特征和异常组织学的RCC进行分类的有用方法。此外，某些基因突变可能是透明细胞RCC及其组织学变体个性化治疗的一个有前景的靶点。
