The Journal of Pathology

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ISSN / EISSN : 0022-3417 / 1096-9896
Published by: Wiley-Blackwell (10.1002)
Total articles ≅ 9,965
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Daniela C. Salles, Kaushal Asrani, Juhyung Woo, Thiago Vidotto, Hans B. Liu, Igor Vidal, Andres Matoso, George J. Netto, Pedram Argani,
Published: 24 January 2022
The Journal of Pathology; https://doi.org/10.1002/path.5875

Abstract:
GPNMB (Glycoprotein nonmetastatic B) and other TFE3/TFEB transcriptional targets have been proposed as markers for MiT translocation renal cell carcinomas (tRCC). We recently demonstrated that constitutive mTORC1 activation via TSC1/2 loss leads to increased activity of TFE3/TFEB, suggesting that the pathogenesis and molecular markers for tRCC and TSC1/2-associated tumors may be overlapping. We examined GPNMB expression in human kidney and angiomyolipoma (AML) cell lines with TSC2 and/or TFE3/TFEB loss produced using CRISPR-Cas9 genome editing as well as in a mouse model of Tsc2 inactivation-driven renal tumorigenesis. Using an automated immunohistochemistry (IHC) assay for GPNMB, digital image analysis was employed to quantitatively score expression in clear cell RCC (ccRCC, n=87), papillary RCC (papRCC, n=53), chromophobe RCC (chRCC, n=34), oncocytoma (n=4), TFE3- or TFEB-driven tRCC (n=56), eosinophilic solid and cystic RCC (ESC, n=6), eosinophilic vacuolated tumor (EVT, n=4) and low grade oncocytic tumor (LOT, n=3) as well as AML (n=29) and PEComa (n=8). In cell lines, GPNMB was up-regulated following TSC2 loss in a MiT/TFE- and mTORC1-dependent fashion. Renal tumors in Tsc2+/- A/J mice showed upregulation of GPNMB compared to normal kidney. Mean GPNMB expression was significantly higher in tRCC compared to ccRCC (p<0.0001), papRCC (p<0.0001) and chRCC (p<0.0001). GPNMB expression in TSC1/2/MTOR alteration-associated renal tumors (including ESC, LOT, AML and PEComa) was comparable to that in tRCC. The immunophenotype of tRCC and TSC1/2/MTOR alteration-associated renal tumors is highly overlapping, likely due to the increased activity of TFE3/TFEB in both, revealing an important caveat regarding the use of TFE3/TFEB-transcriptional targets as diagnostic markers.
Yunjing Yan, Hui Shi, Zhenggang Zhao, Shuai Wang, Sujin Zhou, Yunping Mu, Ning Ding, Yimei Lai, Allan Z. Zhao, Lixian Cheng, et al.
Published: 24 January 2022
The Journal of Pathology; https://doi.org/10.1002/path.5874

The publisher has not yet granted permission to display this abstract.
, Casey G. Langdon, Matthew R. Garcia, Annaleigh Benton, Nadia A. Lanman, David Finkelstein, Jerold E. Rehg,
Published: 23 January 2022
The Journal of Pathology; https://doi.org/10.1002/path.5873

The publisher has not yet granted permission to display this abstract.
Sara Lahoz, Iván Archilla, Elena Asensio, Eva Hernández‐Illán, Queralt Ferrer, Sandra López‐Prades, Ferran Nadeu, Javier del Rey, Rebeca Sanz‐Pamplona, Juan José Lozano, et al.
Published: 23 January 2022
The Journal of Pathology; https://doi.org/10.1002/path.5870

The publisher has not yet granted permission to display this abstract.
Giovanni Di Maira, Beatrice Foglia, Lucia Napione, Cristian Turato, Marina Maggiora, Salvatore Sutti, Erica Novo, Maria Alvaro, Riccardo Autelli, Sebastiano Colombatto, et al.
Published: 22 January 2022
The Journal of Pathology; https://doi.org/10.1002/path.5871

The publisher has not yet granted permission to display this abstract.
, Daniel Pissaloux, Jeremie Poilane, , Anne Tallet, Christine Collin, Matthias Tallegas, Patricia Berthon, Pauline Gaboriaud, Pierre Sohier, et al.
Published: 20 January 2022
The Journal of Pathology; https://doi.org/10.1002/path.5872

The publisher has not yet granted permission to display this abstract.
Huiya Xu, Wei Li, Chongmei Zhu, Na Cheng, Xiaoxia Li, Fengyun Hao, Junfeng Zhu, Liyun Huang, Ran Wang, Liantang Wang, et al.
Published: 18 January 2022
The Journal of Pathology; https://doi.org/10.1002/path.5869

Abstract:
Mucinous tubular and spindle cell carcinoma (MTSCC) is a relatively rare renal epithelial neoplasm resembling type 1 papillary renal cell carcinoma (PRCC) morphologically and immunohistochemically. The accurate diagnosis of MTSCC remains a challenge. Here, by using proteomic profiling, we characterized MTSCC and PRCC to identify diagnostic biomarkers. We found that MTSCC tumor proteome was significantly enriched in B cell-mediated immunity when compared with the proteome of adjacent normal tissues of MTSCC or tumors of PRCC. Importantly, we identified MZB1, VCAN, and SOSTDC1 as diagnostic biomarkers to distinguish MTSCC from solid variant of type 1 PRCC, with an AUC of 0.985 when combined. MZB1 was inversely correlated with tumor clinical stage and may play an anti-tumor role by activating the complement system. Finally, unsupervised clustering revealed two molecular subtypes of MTSCC, displaying different morphology, expression signatures of oxidative phosphorylation, and aggravation. In summary, our analyses identified a three-protein diagnostic panel and molecular subtypes for MTSCC.
Daisuke Yamamoto, Hiroko Oshima, Dong Wang, Haruna Takeda, Kenji Kita, Xuelian Lei, Mizuho Nakayama, Kazuhiro Murakami, Takashi Ohama, Hirofumi Takemura, et al.
Published: 17 January 2022
The Journal of Pathology; https://doi.org/10.1002/path.5868

The publisher has not yet granted permission to display this abstract.
Kelly Mulfaul, Nathaniel K. Mullin, Joseph C. Giacalone, Andrew P. Voigt, Melette DeVore, Edwin M. Stone, Budd A. Tucker,
Published: 17 January 2022
The Journal of Pathology; https://doi.org/10.1002/path.5867

The publisher has not yet granted permission to display this abstract.
, Ruchika Verma, Chuheng Chen, Cheng Lu, Pingfu Fu, Joseph Willis, Anant Madabhushi
Published: 10 January 2022
The Journal of Pathology; https://doi.org/10.1002/path.5864

The publisher has not yet granted permission to display this abstract.
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