Journal of Pathology and Translational Medicine

Original Articles

Histopathologic classification and immunohistochemical features of papillary renal neoplasm with potential therapeutic targets: Jeong Hwan Park, Su-Jin Shin, Hyun-Jung Kim, Sohee Oh, Yong Mee Cho; J Pathol Transl Med. 2024;58(6):321-330. Published online September 12, 2024; DOI: https://doi.org/10.4132/jptm.2024.07.31

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Abstract PDF: Background
Papillary renal cell carcinoma (pRCC) is the second most common histological subtype of renal cell carcinoma and is considered a morphologically and molecularly heterogeneous tumor. Accurate classification and assessment of the immunohistochemical features of possible therapeutic targets are needed for precise patient care. We aimed to evaluate immunohistochemical features and possible therapeutic targets of papillary renal neoplasms
Methods
We collected 140 papillary renal neoplasms from three different hospitals and conducted immunohistochemical studies on tissue microarray slides. We performed succinate dehydrogenase B, fumarate hydratase, and transcription factor E3 immunohistochemical studies for differential diagnosis and re-classified five cases (3.6%) of papillary renal neoplasms. In addition, we conducted c-MET, p16, c-Myc, Ki-67, p53, and stimulator of interferon genes (STING) immunohistochemical studies to evaluate their pathogenesis and value for therapeutic targets.
Results
We found that c-MET expression was more common in pRCC (classic) (p = .021) among papillary renal neoplasms and Ki-67 proliferation index was higher in pRCC (not otherwise specified, NOS) compared to that of pRCC (classic) and papillary neoplasm with reverse polarity (marginal significance, p = .080). Small subsets of cases with p16 block positivity (4.5%) (pRCC [NOS] only) and c-Myc expression (7.1%) (pRCC [classic] only) were found. Also, there were some cases showing STING expression and those cases were associated with increased Ki-67 proliferation index (marginal significance, p = .063).
Conclusions
Our findings suggested that there are subsets of pRCC with c-MET, p16, c-MYC, and STING expression and those cases could be potential candidates for targeted therapy.

Loss of aquaporin-1 expression is associated with worse clinical outcomes in clear cell renal cell carcinoma: an immunohistochemical study: Seokhyeon Lee, Bohyun Kim, Minsun Jung, Kyung Chul Moon; J Pathol Transl Med. 2023;57(4):232-237. Published online July 11, 2023; DOI: https://doi.org/10.4132/jptm.2023.06.17

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Background
Aquaporin (AQP) expression has been investigated in various malignant neoplasms, and the overexpression of AQP is related to poor prognosis in some malignancies. However, the expression of AQP protein in clear cell renal cell carcinoma (ccRCC) has not been extensively investigated by immunohistochemistry with large sample size.
Methods
We evaluated the AQP expression in 827 ccRCC with immunohistochemical staining in tissue microarray blocks and classified the cases into two categories, high and low expression.
Results
High expression of aquaporin-1 (AQP1) was found in 320 cases (38.7%), but aquaporin-3 was not expressed in ccRCC. High AQP1 expression was significantly related to younger age, low TNM stage, low World Health Organization/International Society of Urologic Pathology nuclear grade, and absence of distant metastasis. Furthermore, high AQP1 expression was also significantly associated with longer overall survival (OS; p<.001) and progression-specific survival (PFS; p<.001) and was an independent predictor of OS and PFS in ccRCC.
Conclusions
Our study revealed the prognostic significance of AQP1 protein expression in ccRCC. These findings could be applied to predict the prognosis of ccRCC.

Citations

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Serum Exosomal MiR-874 as a Potential Biomarker for Nonsmall Cell Lung Cancer Diagnosis and Prognosis
Amal F. Gharib, Saad S. Al-Shehri, Abdulraheem Almalki, Ayman Alhazmi, Mamdouh Allahyani, Ahmed Alghamdi, Amani A. Alrehaili, Maha M. Bakhuraysah, Althobaiti Naif Saad M., Weal H. Elsawy
Indian Journal of Medical and Paediatric Oncology.2024;[Epub] CrossRef

Loss of Nuclear BAP1 Expression Is Associated with High WHO/ISUP Grade in Clear Cell Renal Cell Carcinoma: Young Chan Wi, Ahrim Moon, Min Jung Jung, Yeseul Kim, Seong Sik Bang, Kiseok Jang, Seung Sam Paik, Su-Jin Shin; J Pathol Transl Med. 2018;52(6):378-385. Published online October 1, 2018; DOI: https://doi.org/10.4132/jptm.2018.09.21

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Abstract PDF

Background
BRCA1-associated protein 1 (BAP1) mutations are frequently reported in clear cell renal cell carcinoma (ccRCC); however, very few studies have evaluated the role of these mutations in other renal cell carcinoma (RCC) subtypes. Therefore, we analyzed BAP1 protein expression using immunohistochemistry in several RCC subtypes and assessed its relationship with clinicopathological characteristics of patients.
Methods
BAP1 expression was immunohistochemically evaluated in tissue microarray blocks constructed from 371 samples of RCC collected from two medical institutions. BAP1 expression was evaluated based on the extent of nuclear staining in tumor cells, and no expression or expression in < 10% of tumor cells was defined as negative.
Results
Loss of BAP1 expression was observed in ccRCC (56/300, 18.7%), chromophobe RCC (6/26, 23.1%), and clear cell papillary RCC (1/4, 25%), while we failed to detect BAP1 expression loss in papillary RCC, acquired cystic disease-associated RCC, or collecting duct carcinoma. In ccRCC, loss of BAP1 expression was significantly associated with high World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grade (p = .002); however, no significant correlation was observed between loss of BAP1 expression and survival in ccRCC. Loss of BAP1 expression showed no association with prognostic factors in chromophobe RCC.
Conclusions
Loss of BAP1 nuclear expression was observed in both ccRCC and chromophobe RCC. In addition, BAP1 expression loss was associated with poor prognostic factors such as high WHO/ISUP grade in ccRCC.

Citations

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Clinical and Genomic Features of Patients with Renal Cell Carcinoma and Advanced Chronic Kidney Disease: Analysis of a Multi-Institutional Database
Corbin J. Eule, Junxiao Hu, Dale Hedges, Alkesh Jani, Thomas Pshak, Brandon J. Manley, Alejandro Sanchez, Robert Dreicer, Zin W. Myint, Yousef Zakharia, Elaine T. Lam
Cancers.2024; 16(10): 1920. CrossRef
Immune regulation and prognosis indicating ability of a newly constructed multi-genes containing signature in clear cell renal cell carcinoma
Ziwei Gui, Juan Du, Nan Wu, Ningning Shen, Zhiqing Yang, Huijun Yang, Xuzhi Wang, Na Zhao, Zixin Zeng, Rong Wei, Wenxia Ma, Chen Wang
BMC Cancer.2023;[Epub] CrossRef
Radiogenomic Associations Clear Cell Renal Cell Carcinoma: An Exploratory Study
Derek H Liu, Komal A Dani, Sharath S Reddy, Xiaomeng Lei, Natalie L Demirjian, Darryl H Hwang, Bino A Varghese, Suhn Kyong Rhie, Felix Y. Yap, David I. Quinn, Imran Siddiqi, Manju Aron, Ulka Vaishampayan, Haris Zahoor, Steven Y Cen, Inderbir S Gill, Vinay
Oncology.2023; 101(6): 375. CrossRef
Immunohistochemistry for the diagnosis of renal epithelial neoplasms
Mahmut Akgul, Sean R Williamson
Seminars in Diagnostic Pathology.2022; 39(1): 1. CrossRef
BRCA1-Associated Protein 1 (BAP-1) as a Prognostic and Predictive Biomarker in Clear Cell Renal Cell Carcinoma: A Systematic Review
Shuchi Gulati, Melissa Previtera, Primo N. Lara
Kidney Cancer.2022; 6(1): 23. CrossRef
Renal Cell Carcinoma in End-Stage Renal Disease: A Review and Update
Ziad M. El-Zaatari, Luan D. Truong
Biomedicines.2022; 10(3): 657. CrossRef
CD117, BAP1, MTAP, and TdT Is a Useful Immunohistochemical Panel to Distinguish Thymoma from Thymic Carcinoma
Mounika Angirekula, Sindy Y Chang, Sarah M. Jenkins, Patricia T. Greipp, William R. Sukov, Randolph S. Marks, Kenneth R. Olivier, Stephen D. Cassivi, Anja C Roden
Cancers.2022; 14(9): 2299. CrossRef
BAP1 in cancer: epigenetic stability and genome integrity
Sabrina Caporali, Alessio Butera, Ivano Amelio
Discover Oncology.2022;[Epub] CrossRef
Bioinformatic analysis identifying FGF1 gene as a new prognostic indicator in clear cell Renal Cell Carcinoma
Xiaoqin Zhang, Ziyue Wang, Zixin Zeng, Ningning Shen, Bin Wang, Yaping Zhang, Honghong Shen, Wei Lu, Rong Wei, Wenxia Ma, Chen Wang
Cancer Cell International.2021;[Epub] CrossRef
Identification of Four Pathological Stage-Relevant Genes in Association with Progression and Prognosis in Clear Cell Renal Cell Carcinoma by Integrated Bioinformatics Analysis
Dengyong Xu, Yuzi Xu, Yiming Lv, Fei Wu, Yunlong Liu, Ming Zhu, Dake Chen, Bingjun Bai
BioMed Research International.2020; 2020: 1. CrossRef
Functional characterisation guides classification of novel BAP1 germline variants
Jing Han Hong, Siao Ting Chong, Po-Hsien Lee, Jing Tan, Hong Lee Heng, Nur Diana Binte Ishak, Sock Hoai Chan, Bin Tean Teh, Joanne Ngeow
npj Genomic Medicine.2020;[Epub] CrossRef
Tissue-Based Immunohistochemical Markers for Diagnosis and Classification of Renal Cell Carcinoma
Liang G Qu, Vaisnavi Thirugnanasundralingam, Damien Bolton, Antonio Finelli, Nathan Lawrentschuk
Société Internationale d’Urologie Journal.2020; 1(1): 68. CrossRef
Radiogenomics: bridging imaging and genomics
Zuhir Bodalal, Stefano Trebeschi, Thi Dan Linh Nguyen-Kim, Winnie Schats, Regina Beets-Tan
Abdominal Radiology.2019; 44(6): 1960. CrossRef

Case Study

An Intrarenal Adrenocortical Carcinoma Arising in an Adrenal Rest: Ji Hee Lee, Young Deuk Choi, Nam Hoon Cho; J Pathol Transl Med. 2018;52(6):416-419. Published online October 1, 2018; DOI: https://doi.org/10.4132/jptm.2018.07.20

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Abstract PDF

We describe a case of a 61-year-old Korean man who was diagnosed with renal cell carcinoma that was discovered on abdominopelvic computed tomography obtained after the patient complained of back pain. A radical nephrectomy was performed, and the surgical specimen showed a relatively well-circumscribed and yellowish lobulated hard mass. Microscopically, the tumor showed sheets and nests of hypercellular pleomorphic cells with thick fibrous septation, frequent mitoses, and areas of adrenal cortical-like tissue. Immunohistochemical staining revealed that the tumor cells were positive for inhibin-α, vimentin, synaptophysin, and melan A. It also revealed that the tumor cells were negative for pan-cytokeratin, epithelial membrane antigen, paired box 8, α-methylacyl-coenzyme A racemase, CD10, cytokeratin 7, carbonic anhydrase 9, c-Kit, renal cell carcinoma, transcription factor E3, human melanoma black 45, desmin, smooth muscle actin, S-100, chromogranin A, CD34, anaplastic lymphoma kinase, and integrase interactor 1. Based on these histopathological and immunohistochemical findings, we diagnosed the tumor as intrarenal adrenocortical carcinoma arising in an adrenal rest. Several cases of intrarenal adrenocortical carcinoma have been reported, although they are very rare. Due to its poor prognosis and common recurrence or metastasis, clinicians and pathologists must be aware of this entity.

Citations

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Non-functional Adrenocortical Carcinoma in the Wall of the Small Bowel
Shu-Juan Lin, Yan Gao, Chun-Juan Sun
Current Medical Imaging Reviews.2023;[Epub] CrossRef
Ectopic adrenal tissue in the kidney: A systematic review
Davide De Marchi, Alessandro Tafuri, Guglielmo Mantica, Aliasger Shakir, Federico Scarfò, Giovanni Passaretti, Salvatore Smelzo, Silvia Proietti, Lorenzo Rigatti, Roberta Luciano, Alessandro Antonelli, Vincenzo Pagliarulo, Rosario Leonardi, Gu
Archivio Italiano di Urologia e Andrologia.2021; 93(4): 481. CrossRef
Extra-adrenal, non-functional adrenocortical carcinoma presenting with acute abdomen: a case report
Alireza Mirsharifi, Mohammad Vasei, Ehsan Sadeghian, Ali Ghorbani-Abdehgah, Sara Naybandi Atashi
Journal of Medical Case Reports.2020;[Epub] CrossRef
Testicular Adrenal Rest Tumors: Current Insights on Prevalence, Characteristics, Origin, and Treatment
Manon Engels, Paul N Span, Antonius E van Herwaarden, Fred C G J Sweep, Nike M M L Stikkelbroeck, Hedi L Claahsen-van der Grinten
Endocrine Reviews.2019; 40(4): 973. CrossRef

Original Articles

Significance of Intratumoral Fibrosis in Clear Cell Renal Cell Carcinoma: Jae Won Joung, Hoon Kyu Oh, Sun Jae Lee, Young Ah Kim, Hyun Jin Jung; J Pathol Transl Med. 2018;52(5):323-330. Published online August 19, 2018; DOI: https://doi.org/10.4132/jptm.2018.07.21

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Abstract PDF

Background
Intratumoral fibrosis (ITF) is a frequent histologic finding in solid organ tumors. Renal cell carcinoma (RCC) is a highly vascularized tumor with different shapes and degrees of ITF and inflammation. ITF is a poor prognostic factor, especially in breast cancer, and is related to intratumoral necrosis (ITN) and intratumoral inflammation (ITI). However, the significance of ITF in RCC has not been fully studied. In this study, we evaluate the relationships between ITF and other clinicopathologic parameters associated with RCC prognosis.
Methods
ITF was evaluated in 204 clear cell renal cell carcinoma (CCRCC) specimens according to presence and grade of fibrosis, degree of ITI, and presence of ITN. Lysyl oxidase (LOX) expression in tumor cells was also evaluated with clinicopathologic parameters.
Results
Among 204 CCRCC cases, 167 (81.7%) showed ITF, 71 (34.8%) showed ITI, 35 (17.2%) showed ITN, and 111 (54.4%) showed LOX expression. ITF correlated with Fuhrman nuclear grade (p = .046), lymphovascular invasion (LVI) (p = .027), and ITN (p = .036). Patients with ITF had a poor five-year overall survival rate (p = .104).
Conclusions
ITF is related to other poor prognostic factors in CCRCC, such as Fuhrman nuclear grade, ITN, and LVI, but ITF itself had no significant correlation with prognosis of CCRCC.

Citations

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New insights into fibrotic signaling in renal cell carcinoma
Jiao-Yi Chen, Wai-Han Yiu, Patrick Ming-Kuen Tang, Sydney Chi-Wai Tang
Frontiers in Cell and Developmental Biology.2023;[Epub] CrossRef
Tumor-associated fibrosis impairs the response to immunotherapy
Angha Naik, Andrew Leask
Matrix Biology.2023; 119: 125. CrossRef
Decreased renal expression of PAQR5 is associated with the absence of a nephroprotective effect of progesterone in a rat UUO model
P. A. Abramicheva, D. S. Semenovich, L. D. Zorova, I. B. Pevzner, I. A. Sokolov, V. A. Popkov, E. P. Kazakov, D. B. Zorov, E. Y. Plotnikov
Scientific Reports.2023;[Epub] CrossRef
Intratumoral fibrosis and patterns of immune infiltration in clear cell renal cell carcinoma
Songchen Han, Wenbo Yang, Caipeng Qin, Yiqing Du, Mengting Ding, Huaqi Yin, Tao Xu
BMC Cancer.2022;[Epub] CrossRef
Siglec-F–expressing neutrophils are essential for creating a profibrotic microenvironment in renal fibrosis
Seungwon Ryu, Jae Woo Shin, Soie Kwon, Jiwon Lee, Yong Chul Kim, Yoe-Sik Bae, Yong-Soo Bae, Dong Ki Kim, Yon Su Kim, Seung Hee Yang, Hye Young Kim
Journal of Clinical Investigation.2022;[Epub] CrossRef
The atypical sphingosine 1‐phosphate variant, d16:1 S1P, mediates CTGF induction via S1P2 activation in renal cell carcinoma
Melanie Glueck, Alexander Koch, Robert Brunkhorst, Nerea Ferreiros Bouzas, Sandra Trautmann, Liliana Schaefer, Waltraud Pfeilschifter, Josef Pfeilschifter, Rajkumar Vutukuri
The FEBS Journal.2022; 289(18): 5670. CrossRef
The Synergistic Cooperation between TGF-β and Hypoxia in Cancer and Fibrosis
Pramod Mallikarjuna, Yang Zhou, Maréne Landström
Biomolecules.2022; 12(5): 635. CrossRef
In Vitro Characterization of Renal Drug Transporter Activity in Kidney Cancer
Pedro Caetano-Pinto, Nathanil Justian, Maria Dib, Jana Fischer, Maryna Somova, Martin Burchardt, Ingmar Wolff
International Journal of Molecular Sciences.2022; 23(17): 10177. CrossRef
PD-1 immunobiology in glomerulonephritis and renal cell carcinoma
Colleen S. Curran, Jeffrey B. Kopp
BMC Nephrology.2021;[Epub] CrossRef
Intratumoral Fibrosis in Facilitating Renal Cancer Aggressiveness: Underlying Mechanisms and Promising Targets
Chao Hu, Yufeng Zhao, Xuanchuan Wang, Tongyu Zhu
Frontiers in Cell and Developmental Biology.2021;[Epub] CrossRef
What Mediates Fibrosis in the Tumor Microenvironment of Clear Renal Cell Carcinoma
Wenbo Yang, Caipeng Qin, Jingli Han, Songchen Han, Wenjun Bai, Yiqing Du, Tao Xu
Frontiers in Genetics.2021;[Epub] CrossRef
Kidney Cancer and Chronic Kidney Disease: Too Close for Comfort
Pedro Caetano Pinto, Cindy Rönnau, Martin Burchardt, Ingmar Wolff
Biomedicines.2021; 9(12): 1761. CrossRef
The Significance of Fibrosis Quantification as a Marker in Assessing Pseudo-Capsule Status and Clear Cell Renal Cell Carcinoma Prognosis
Caipeng Qin, Huaqi Yin, Huixin Liu, Feng Liu, Yiqing Du, Tao Xu
Diagnostics.2020; 10(11): 895. CrossRef
The challenges of adoptive cell transfer in the treatment of human renal cell carcinoma
Zuzana Strizova, Jirina Bartunkova, Daniel Smrz
Cancer Immunology, Immunotherapy.2019; 68(11): 1831. CrossRef
Procollagen-lysine, 2-oxoglutarate 5-dioxygenases 1, 2, and 3 are potential prognostic indicators in patients with clear cell renal cell carcinoma
Wen-Hao Xu, Yue Xu, Jun Wang, Xi Tian, Junlong Wu, Fang-Ning Wan, Hong-Kai Wang, Yuan-Yuan Qu, Hai-Liang Zhang, Ding-Wei Ye
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Implication of PHF2 Expression in Clear Cell Renal Cell Carcinoma: Cheol Lee, Bohyun Kim, Boram Song, Kyung Chul Moon; J Pathol Transl Med. 2017;51(4):359-364. Published online June 13, 2017; DOI: https://doi.org/10.4132/jptm.2017.03.16

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Abstract PDF

Background
Clear cell renal cell carcinoma (CCRCC) is presumed to be associated with adipogenic differentiation. Histone modification is known to be important for adipogenesis, and the function of histone demethylase plant homeodomain finger 2 (PHF2) has been noted. In addition, PHF2 may act as a tumor suppressor via epigenetic regulation of p53 and is reported to be reduced in colon cancer and stomach cancer tissues. In this study, we examined PHF2 expression in CCRCC specimens by immunohistochemistry.
Methods
We studied 254 CCRCCs and 56 non-neoplastic renal tissues from patients who underwent radical or partial nephrectomy between 2000 and 2003 at the Seoul National University Hospital. Tissue microarray blocks were prepared, and immunohistochemical staining for PHF2 was performed.
Results
Among 254 CCRCC cases, 150 cases (59.1%) showed high expression and 104 cases (40.1%) showed low expression. High expression of PHF2 was significantly correlated with a low Fuhrman nuclear grade (p < .001), smaller tumor size (p < .001), low overall stage (p = .003), longer cancer-specific survival (p = .002), and progression-free survival (p < .001) of the patients. However, it was not an independent prognostic factor in multivariate analysis adjusted for Fuhrman nuclear grade and overall stage.
Conclusions
Our study showed that low expression of PHF2 is associated with aggressiveness and poor prognosis of CCRCC.

Citations

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The role of histone methylation in renal cell cancer: an update
Yanguang Hou, Yan Yuan, Yanze Li, Lei Wang, Juncheng Hu, Xiuheng Liu
Molecular Biology Reports.2023; 50(3): 2735. CrossRef
Phosphorylation of PHF2 by AMPK releases the repressive H3K9me2 and inhibits cancer metastasis
Ying Dong, Hao Hu, Xuan Zhang, Yunkai Zhang, Xin Sun, Hanlin Wang, Weijuan Kan, Min-jia Tan, Hong Shi, Yi Zang, Jia Li
Signal Transduction and Targeted Therapy.2023;[Epub] CrossRef
HIF-1α-mediated augmentation of miRNA-18b-5p facilitates proliferation and metastasis in osteosarcoma through attenuation PHF2
Peng Luo, Yan-dong Zhang, Feng He, Chang-jun Tong, Kai Liu, He Liu, Shi-zhuang Zhu, Jian-zhou Luo, Bing Yuan
Scientific Reports.2022;[Epub] CrossRef
Integration of meta-analysis and supervised machine learning for pattern recognition in breast cancer using epigenetic data
Reza Panahi, Esmaeil Ebrahimie, Ali Niazi, Alireza Afsharifar
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PHF2 regulates homology-directed DNA repair by controlling the resection of DNA double strand breaks
Ignacio Alonso-de Vega, Maria Cristina Paz-Cabrera, Magdalena B Rother, Wouter W Wiegant, Cintia Checa-Rodríguez, Juan Ramón Hernández-Fernaud, Pablo Huertas, Raimundo Freire, Haico van Attikum, Veronique A J Smits
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Emerging of lysine demethylases (KDMs): From pathophysiological insights to novel therapeutic opportunities
Sarder Arifuzzaman, Mst Reshma Khatun, Rabeya Khatun
Biomedicine & Pharmacotherapy.2020; 129: 110392. CrossRef
Biology and targeting of the Jumonji-domain histone demethylase family in childhood neoplasia: a preclinical overview
Tyler S. McCann, Lays M. Sobral, Chelsea Self, Joseph Hsieh, Marybeth Sechler, Paul Jedlicka
Expert Opinion on Therapeutic Targets.2019; 23(4): 267. CrossRef
MiR-221 Promotes Hepatocellular Carcinoma Cells Migration via Targeting PHF2
Yi Fu, Mingyan Liu, Fengxia Li, Li Qian, Ping Zhang, Fengwei Lv, Wenting Cheng, Ruixing Hou
BioMed Research International.2019; 2019: 1. CrossRef
PHF2 histone demethylase prevents DNA damage and genome instability by controlling cell cycle progression of neural progenitors
Stella Pappa, Natalia Padilla, Simona Iacobucci, Marta Vicioso, Elena Álvarez de la Campa, Claudia Navarro, Elia Marcos, Xavier de la Cruz, Marian A. Martínez-Balbás
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Plant homeodomain finger protein 2 as a novel IKAROS target in acute lymphoblastic leukemia
Zheng Ge, Yan Gu, Qi Han, Justin Sloane, Qinyu Ge, Goufeng Gao, Jinlong Ma, Huihui Song, Jiaojiao Hu, Baoan Chen, Sinisa Dovat, Chunhua Song
Epigenomics.2018; 10(1): 59. CrossRef

Case Studies

Clear Cell Renal Cell Carcinoma with Intratumoral Granulomatous Reaction: A Case Report and Review of the Literature: Hayeon Kim, Jong Wook Kim, Aeree Kim, Hyeyoon Chang; J Pathol Transl Med. 2017;51(3):325-328. Published online March 14, 2017; DOI: https://doi.org/10.4132/jptm.2016.09.08

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Abstract PDF: Granulomatous reaction associated with clear cell renal cell carcinoma (CCRCC) is a rare finding, and only a few cases have been described in the literature. It is postulated to occur due to cancer- related antigenic factors such as cancer cells themselves or soluble tumor antigens shed into the blood. Herein, we describe a case of a 56-year-old male patient diagnosed with CCRCC with intratumoral granulomatous inflammation.

Oncocytic Renal Cell Carcinoma with Tubulopapillary Growth Having a Fat Component: Na Rae Kim, Hyun Yee Cho; J Pathol Transl Med. 2015;49(5):413-417. Published online July 30, 2015; DOI: https://doi.org/10.4132/jptm.2015.07.01

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Abstract PDF: We report a rare case of oncocytic renal cell carcinoma (RCC) with tubulopapillary growth in the background of tuberculous end-stage kidney disease. Histology of the renal mass consisted of oncocytic cells forming solid, thin tubules and rare papillae. The tumor had abundant eosinophilic oncocytic cells containing occasional cytoplasmic Mallory body–like hyaline globules and a tiny focus of clear cells with intervening mature fat. Both the oncocytic cells and clear cells were immunoreactive for a-methylacyl-CoA racemase, vimentin, pancytokeratin, and CD10, and negative for transcription factor E3, CD15, human melanoma black 45, and c-kit. Mallory body–like hyaline globules were positive for CAM 5.2 and periodic acid–Schiff with or without diastase. Ultrastructurally, the tumor cells had abundant cytoplasmic mitochondria. The present case is a rare case of oncocytic RCC with tubulopapillary growth pattern. The case is unique in that the tumor was mixed with fat component, which is not common in RCC and thus can lead to misdiagnosis.

Original Articles

Transglutaminase 2 Expression and Its Prognostic Significance in Clear Cell Renal Cell Carcinoma: Min Jee Park, Hae Woon Baek, Ye-Young Rhee, Cheol Lee, Jeong Whan Park, Hwal Woong Kim, Kyung Chul Moon; J Pathol Transl Med. 2015;49(1):37-43. Published online January 15, 2015; DOI: https://doi.org/10.4132/jptm.2014.10.25

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Abstract PDF

Background
A few recent studies have demonstrated a possible role of transglutaminase 2 (TG2) in tumorigenesis or progression of renal cell carcinoma (RCC). The aim of this study was to examine TG2 expression and its clinicopathologic significance in a large number of human clear cell RCCs (CCRCCs). Methods: We analyzed 638 CCRCC patients who underwent partial or radical nephrectomy between 1995 and 2005. The expression of TG2 was determined by immunohistochemistry and categorized into four groups, according to staining intensity: negative (0), mild (1+), moderate (2+), and strong (3+). Results: TG2 staining intensity was negative in 8.5% of CCRCC (n=54), 1+ in 32.6% (n=208), 2+ in 50.5% (n=322), and 3+ in 8.5% (n=54). Strong TG2 expression was correlated with high Fuhrman nuclear grade (p=.011), high T category (p=.049), metastasis (p=.043) and male sex (p<.001) but not with N category.The survival analysis showed a significant association between strong TG2 expression and worse overall and cancer-specific survival (p=.027 and p=.010, respectively). On multivariate analysis, strong TG2 expression was a marginally significant prognostic indicator for Fuhrman nuclear grade and TNM staging (p=.054). Conclusions: Our study is the first to demonstrate the clinicopathologic significance of TG2 expression in a large number of human CCRCC samples. Strong TG2 expression was associated with high nuclear grade and poor prognosis.

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Burge Ulukan, Ajna Bihorac, Tarik Sipahioglu, Robert Kiraly, Laszlo Fesus, Dilek Telci
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Renal Cell Carcinoma Is Abrogated by p53 Stabilization through Transglutaminase 2 Inhibition
Seon-Hyeong Lee, Won-Kyu Lee, Nayeon Kim, Joon Hee Kang, Kyung-Hee Kim, Seul-Gi Kim, Jae-Seon Lee, Soohyun Lee, Jongkook Lee, Jungnam Joo, Woo Sun Kwon, Sun Young Rha, Soo-Youl Kim
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Tissue transglutaminase expression is necessary for adhesion, metastatic potential and cancer stemness of renal cell carcinoma
Yesim Bagatur, Ayca Zeynep Ilter Akulke, Ajna Bihorac, Merve Erdem, Dilek Telci
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Bryan J. Thibodeau, Matthew Fulton, Laura E. Fortier, Timothy J. Geddes, Barbara L. Pruetz, Samreen Ahmed, Amy Banes-Berceli, Ping L. Zhang, George D. Wilson, Jason Hafron
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María Jesús Fernández-Aceñero, Sofía Torres, Irene Garcia-Palmero, Cristina Díaz del Arco, J. Ignacio Casal
Virchows Archiv.2016; 469(6): 611. CrossRef

IMP3, a Promising Prognostic Marker in Clear Cell Renal Cell Carcinoma: Ji Young Park, Misun Choe, Yuna Kang, Sang Sook Lee; Korean J Pathol. 2014;48(2):108-116. Published online April 28, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.2.108

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Abstract PDF

Background

Insulin-like growth factor II mRNA-binding protein 3 (IMP3) has been reported as a prognostic biomarker in various cancers. To validate IMP3 as a prognostic biomarker in renal cell carcinoma (RCC), we investigated the expression of IMP3, p53, and Ki-67, and their associations with clinicopathologic outcomes.

Methods

We studied 148 clear cell RCCs (CCRCCs) from patients who underwent radical nephrectomy. The expression levels of IMP3, p53, and Ki-67 were assessed by immunohistochemical staining and the clinical and pathologic parameters were retrospectively reviewed.

Results

Twenty-nine percent of CCRCCs expressed IMP3. Forty-one percent of IMP3-immunopositive tumors developed metastases, while only 11.4% of IMP3-negative tumors developed metastases (p<.001). A Kaplan-Meier curve showed that patients with IMP3-immunopositive tumors had lower metastasis-free survival and cancer-specific survival than did those with IMP3-immunonegative tumors (p<.001 and p<.001, respectively). Expression of high Ki-67 proliferation index was also associated with a higher metastatic rate. In the multivariate Cox regression analysis, pT stage and IMP3-positivity were independently associated with disease-specific survival.

Conclusions

IMP3 is an independent prognostic biomarker for patients with CCRCC to predict metastasis and poor outcome.

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Natividad Martin-Morales, Miguel Padial-Molina, Isabel Tovar, Virginea De Araujo Farias, Pedro Hernández-Cortés, Esperanza Ramirez-Moreno, Mercedes Caba-Molina, Justin Davis, Alejandro Carrero Castaño, Jose Mariano Ruiz de Almodovar, Pablo Galindo-Moreno,
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circRARS synergises with IGF2BP3 to regulate RNA methylation recognition to promote tumour progression in renal cell carcinoma
Yuenan Liu, Kailei Chen, Yi Shou, Sen Li, Jun Wang, Qingyang Zhang, Ziwei Huang, Jiaju Xu, Mingfeng Li, Di Liu, Huageng Liang, Hongmei Yang, Xiaoping Zhang
Clinical and Translational Medicine.2023;[Epub] CrossRef
Prognostic value of insulin‑like growth factor 2 mRNA‑binding protein 3 and vascular endothelial growth factor‑A in patients with primary non‑small‑cell lung cancer
Jiannan Liu, Ying Liu, Wenjing Gong, Xiangshuo Kong, Congcong Wang, Shuhua Wang, Aina Liu
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Epithelial‑mesenchymal transition in colorectal carcinoma cells is mediated by DEK/IMP3
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Renal Histologic Parameters Influencing Postoperative Renal Function in Renal Cell Carcinoma Patients: Myoung Ju Koh, Beom Jin Lim, Kyu Hun Choi, Yon Hee Kim, Hyeon Joo Jeong; Korean J Pathol. 2013;47(6):557-562. Published online December 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.6.557

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Abstract PDF

Background

Pre-existing non-neoplastic renal diseases or lesions may influence patient renal function after tumor removal. However, its description is often neglected or omitted in pathologic reports. To determine the incidence and clinical significance of non-neoplastic lesions, we retrospectively examined renal tissues obtained during 85 radical nephrectomies for renal cell carcinoma.

Methods

One paraffin-embedded tissue block from each case containing a sufficient amount of non-tumorous renal parenchyma was cut and processed with hematoxylin and eosin and periodic acid-Schiff methods. Non-neoplastic lesions of each histological compartment were semi-quantitatively and quantitatively evaluated.

Results

Among the various histologic lesions found, tubular atrophy, arterial intimal thickening, and glomerulosclerosis were the most common (94.1%, 91.8%, and 88.2%, respectively). Glomerulosclerosis correlated with estimated glomerular filtration rate at the time of surgery, as well as at 1- and 5-years post-surgery (p=.0071), but tubulointerstitial fibrosis or arterial fibrous intimal thickening did not. Post-hoc analysis revealed that glomerulosclerosis of more than 20% predicted post-operative renal function. However, its significance disappeared when gender and age were considered.

Conclusions

In conclusion, non-neoplastic lesions, especially with regard to glomerulosclerosis percentage, should be described in pathology reports to provide additional information on renal function decline.

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Amira R. Mahmoud, Nehad Fouda, Eman Mohamed Helmy, Ali Elsorougy
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Chronic kidney damage pathology score for systematic assessment of the non-neoplastic kidney tissue and prediction of post-operative renal function outcomes
Yong Jia, Seyed M.M. Poor, Brenden Dufault, Vivian Lu, Jasmir G. Nayak, Deepak K. Pruthi, Ian W. Gibson
Human Pathology.2022; 124: 76. CrossRef
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Qingqiang Zhu, Wenrong Zhu, Jing Ye, Jingtao Wu, Wenxin Chen, Zhihua Hao
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Conventional and Papillary Renal Cell Carcinomas and Focal Segmental Glomerulosclerosis in a Nephrectomy
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ALK-Positive Renal Cell Carcinoma in a Large Series of Consecutively Resected Korean Renal Cell Carcinoma Patients: Cheol Lee, Jeong Whan Park, Ja Hee Suh, Kyung Han Nam, Kyung Chul Moon; Korean J Pathol. 2013;47(5):452-457. Published online October 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.5.452

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Abstract PDF

Background

Recently, there have been a few reports of renal cell carcinoma (RCC) cases with anaplastic lymphoma kinase (ALK) gene fusion. In this study, we screened consecutively resected RCCs from a single institution for ALK protein expression by immunohistochemistry, and then we performed fluorescence in situ hybridization to confirm the ALK gene alteration in ALK immunohistochemistry-positive cases.

Methods

We screened 829 RCCs by ALK immunohistochemistry, and performed fluorescence in situ hybridization analysis using ALK dual-color break-apart rearrangement probe. Histological review and additional immunohistochemistry analyses were done in positive cases.

Results

One ALK-positive case was found. Initial diagnosis of this case was papillary RCC type 2. This comprises 0.12% of all RCCs (1/829) and 1.9% of papillary RCCs (1/53). This patient was a 44-year-old male with RCC found during routine health check-up. He was alive without evidence of disease 12 years after surgery. The tumor showed a papillary and tubular pattern, and showed positivity for CD10 (focal), epithelial membrane antigen, cytokeratin 7, pan-cytokeratin, PAX-2, and vimentin.

Conclusions

We found the first RCC case with ALK gene rearrangement in Korean patients by ALK immunohistochemistry among 829 RCCs. This case showed similar histological and immunohistochemical features to those of previous adult cases with ALK rearrangement, and showed relatively good prognosis.

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Histologic Variations and Immunohistochemical Features of Metastatic Clear Cell Renal Cell Carcinoma: Cheol Lee, Jeong-Whan Park, Ja Hee Suh, Kyung Han Nam, Kyung Chul Moon; Korean J Pathol. 2013;47(5):426-432. Published online October 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.5.426

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Abstract PDF

Background

Due to advancements in treatment of metastatic and advanced renal cell carcinoma (RCC), it has become increasingly important to diagnose metastatic RCC and the specific subtype. In this study, we investigated the diverse histologic features of metastatic clear cell renal cell carcinoma (CCRCC) cases in comparison with corresponding primary lesions.

Methods

We identified 119 metastatic CCRCC cases from 81 corresponding primary lesions diagnosed between 1995 and 2010 and evaluated the diverse histologic and immunohistochemical features of these lesions.

Results

A total of 44 primary lesions (54.3%) had a non-clear cell component in addition to a typical clear cell component. Of the 119 metastatic lesions, 63 lesions (52.9%) contained a non-clear cell component, and 29 metastatic lesions were composed of a non-clear cell component only. Rhabdoid features were the most frequent non-clear cell histology among the metastatic lesions. Metastatic CCRCCs mainly showed positive CD10 and epithelial membrane antigen staining and negative cytokeratin 7 staining.

Conclusions

Metastatic CCRCC commonly showed a variety of histologic features. If there is a difficulty to diagnose metastatic CCRCC due to a variety of histologic features or small biopsy specimen, histologic review of the primary lesion and immunohistochemical analysis can help determine the correct diagnosis.

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Adebowale J. Adeniran, Brian Shuch, Peter A. Humphrey
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Clear Cell Papillary Renal Cell Carcinoma: A Report of 15 Cases Including Three Cases of Concurrent Other-Type Renal Cell Carcinomas: Jeong Hwan Park, Cheol Lee, Ja Hee Suh, Kyung Chul Moon; Korean J Pathol. 2012;46(6):541-547. Published online December 26, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.6.541

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Abstract PDF

Background

Clear cell papillary renal cell carcinoma (CCPRCC) is a recently established subtype of renal epithelial tumor. The aim of this study was to identify the diagnostic criteria of CCPRCC with an emphasis on immunohistochemical studies, and to report three cases with concurrent other-type renal cell carcinoma (RCC).

Methods

A total of 515 RCC patients that consecutively underwent surgical resection at Seoul National University Hospital from 1 January 2010 to 31 December 2011 were screened. Each case was reviewed based on the histologic features and was evaluated immunohistochemically.

Results

A total of 15 CCPRCCs were identified, which composed 2.9% of the total RCCs. The mean age was 52 years, and the average tumor size was 1.65 cm. All 15 cases showed low nuclear grade, no lymph node metastasis and no distant metastasis. The CCPRCCs showed variable architectural patterns including cystic, trabecular, papillary, and acinar. All of the cases showed moderate to intense immunoreactivity for cytokeratin 7 (CK7). CD10 was negative or showed focal weak positivity. Three cases had concurrent other-type RCC, including a clear cell RCC and an acquired cystic disease-associated RCC.

Conclusions

The strong CK7 and negative or focal weak CD10 expression will be useful for the diagnosis of CCPRCC.

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Case Report

Multifocal Renal Cell Carcinoma of Different Histological Subtypes in Autosomal Dominant Polycystic Kidney Disease: Ki Yong Na, Hyun-Soo Kim, Yong-Koo Park, Sung-Goo Chang, Youn Wha Kim; Korean J Pathol. 2012;46(4):382-386. Published online August 23, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.4.382

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Abstract PDF

Renal cell carcinoma (RCC) in autosomal dominant polycystic kidney (ADPKD) is rare. To date, 54 cases of RCC in ADPKD have been reported. Among these, only 2 cases have different histologic types of RCC. Here we describe a 45-year-old man who received radical nephrectomy for multifocal RCC with synchronous papillary and clear cell histology in ADPKD and chronic renal failure under regular hemodialysis. The case reported herein is another example of the rare pathological finding of RCC arising in a patient with ADPKD.

Citations

Citations to this article as recorded by

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