Expression of L1 Cell Adhesion Molecule, a Nephronal Principal Cell Marker, in Nephrogenic Adenoma

IF 7.1 1区 医学 Q1 PATHOLOGY Modern Pathology Pub Date : 2024-06-18 DOI:10.1016/j.modpat.2024.100540
Rahul Mannan , Xiaoming Wang , Somnath Mahapatra , Susanna Wang , Anya K. Chinnaiyan , Stephanie L. Skala , Yuping Zhang , Lisa M. McMurry , Sylvia Zelenka-Wang , Xuhong Cao , Ankur R. Sangoi , Vipulkumar Dadhania , Maria M. Picken , Santosh Menon , Hikmat Al-Ahmadie , Arul M. Chinnaiyan , Saravana M. Dhanasekaran , Rohit Mehra
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Abstract

Nephrogenic adenoma (NA) is a benign, reactive lesion seen predominantly in the urinary bladder and often associated with antecedent inflammation, instrumentation, or an operative history. Its histopathologic diversity can create diagnostic dilemmas and pathologists use morphologic evaluation along with available immunohistochemical (IHC) markers to navigate these challenges. IHC assays currently do not designate or specify NA’s potential putative cell of origin. Leveraging single-cell RNA-sequencing technology, we nominated a principal (P) cell–collecting duct marker, L1 cell adhesion molecule (L1CAM), as a potential biomarker for NA. IHC characterization revealed L1CAM to be positive in all 35 (100%) patient samples of NA; negative expression was seen in the benign urothelium, benign prostatic glands, urothelial carcinoma (UCA) in situ, prostatic adenocarcinoma, majority of high-grade UCA, and metastatic UCA. In the study, we also used single-cell RNA sequencing to nominate a novel compendium of biomarkers specific for the proximal tubule, loop of Henle, and distal tubule (DT) (including P and intercalated cells), which can be used to perform nephronal mapping using RNA in situ hybridization and IHC technology. Employing this technique on NA we found enrichment of both the P-cell marker L1CAM and, the proximal tubule type-A and -B cell markers, PDZKI1P1 and PIGR, respectively. The cell-type markers for the intercalated cell of DTs (LINC01187 and FOXI1), and the loop of Henle (UMOD and IRX5), were found to be uniformly absent in NA. Overall, our findings show that based on cell type–specific implications of L1CAM expression, the shared expression pattern of L1CAM between DT P cells and NA. L1CAM expression will be of potential value in assisting surgical pathologists toward a diagnosis of NA in challenging patient samples.

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肾源性腺瘤中肾主细胞标志物 L1 细胞粘附分子 (L1CAM) 的表达
肾腺瘤是一种主要见于膀胱的良性反应性病变,通常与前驱炎症、器械操作或手术史有关。其组织病理学的多样性会造成诊断上的困境,病理学家利用形态学评估和可用的免疫组化标记来应对这些挑战。目前,免疫组化检测并不能指定或明确肾腺瘤的潜在原发细胞。利用单细胞 RNA 测序技术,我们确定了一种主要的细胞收集管标记--L1 细胞粘附分子(L1CAM)--作为肾腺瘤的潜在生物标记。免疫组化鉴定显示,35 例(100%)肾源性腺瘤患者样本中的 L1CAM 均为阳性;良性尿路上皮、良性前列腺、尿路上皮原位癌、前列腺腺癌、大部分高级别尿路上皮癌和转移性尿路上皮癌中的 L1CAM 均为阴性表达。在这项研究中,我们还利用单细胞 RNA 测序技术,为近端肾小管、亨列襻和远端肾小管(包括主细胞和闰细胞)确定了一系列新的特异性生物标记物,这些标记物可用于利用 RNA 原位杂交和免疫组化技术绘制肾小球图谱。通过对肾腺瘤采用这种技术,我们发现主细胞标志物 L1CAM 以及近端小管 A 型和 B 型细胞标志物 PDZKI1P1 和 PIGR 都富集了。远端肾小管闰层细胞(LINC01187 和 FOXI1)和亨列襻细胞(UMOD 和 IRX5)的细胞类型标记物在肾腺瘤中则一致缺失。总之,我们的研究结果表明,根据 L1CAM 表达的细胞类型特异性影响,远端肾小管主细胞(P)和肾腺瘤之间存在 L1CAM 的共同表达模式。L1CAM 的表达在协助外科病理学家诊断具有挑战性的患者样本中的肾腺瘤方面具有潜在价值。
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来源期刊
Modern Pathology
Modern Pathology 医学-病理学
CiteScore
14.30
自引率
2.70%
发文量
174
审稿时长
18 days
期刊介绍: Modern Pathology, an international journal under the ownership of The United States & Canadian Academy of Pathology (USCAP), serves as an authoritative platform for publishing top-tier clinical and translational research studies in pathology. Original manuscripts are the primary focus of Modern Pathology, complemented by impactful editorials, reviews, and practice guidelines covering all facets of precision diagnostics in human pathology. The journal's scope includes advancements in molecular diagnostics and genomic classifications of diseases, breakthroughs in immune-oncology, computational science, applied bioinformatics, and digital pathology.
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