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- 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
- 1,736 View
- 327 Download
- 1 Crossref
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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. -
Citations
Citations to this article as recorded by
- Tissue-Based Biomarkers Important for Prognostication and Management of Genitourinary Tumors, Including Surrogate Markers of Genomic Alterations
Leonie Beauchamp, Shreeya Indulkar, Eric Erak, Mohammad Salimian, Andres Matoso
Surgical Pathology Clinics.2025; 18(1): 175. CrossRef
- Tissue-Based Biomarkers Important for Prognostication and Management of Genitourinary Tumors, Including Surrogate Markers of Genomic Alterations
- Expression of c-MET in Invasive Meningioma
- Sumi Yun, Jae Moon Koh, Kyu Sang Lee, An Na Seo, Kyung Han Nam, Gheeyoung Choe
- J Pathol Transl Med. 2015;49(1):44-51. Published online January 15, 2015
- DOI: https://doi.org/10.4132/jptm.2014.10.13
- 10,105 View
- 72 Download
- 23 Web of Science
- 21 Crossref
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Abstract
PDF
- Background
Meningiomas show high recurrence rates even after curative tumor removal. The invasiveness of meningiomas may contribute to their high recurrence rates. Recently, c-MET and hepatocyte growth factor (HGF) have been reported to be involved in cancer invasion. Methods: We examined the immunohistochemical expression of c-MET and HGF in 100 cases of patients with meningiomas who have undergone complete tumor removal. Results: c-MET-High and HGFHigh were found in 17% and 13% of meningiomas, respectively. Brain invasion was observed in 17.6% of c-MET-High meningiomas, but in only 2.4% of c-MET-Low meningiomas (p=.033). Bone/ soft tissue invasion was observed in 23.5% of c-MET-High meningiomas and in 9.6% of c-MET-Low meningiomas (p=.119). HGF-High did not show statistical association with brain invasion or bone/ soft tissue invasion. c-MET-High demonstrated shorter recurrence-free survival (RFS, 93.5±8.2 months vs 96.1±1.9 months); however, this difference was not statistically significant (p=.139). There was no association of HGF-High with RFS. Conclusions: This study demonstrates that c- MET-High is associated with brain invasion of meningiomas, and that c-MET expression may be a useful predictive marker for meningioma recurrence. Patients with invasive meningiomas with high expressions of c-MET may be good candidates for targeted therapy using c-MET inhibitors. -
Citations
Citations to this article as recorded by- MRI morphological features combined with apparent diffusion coefficient can predict brain invasion in meningioma
Xiaoyu Huang, Yuntai Cao, Guojin Zhang, FuQiang Tang, Dandan Sun, Jialiang Ren, Wenyi Li, Junlin Zhou, Jing Zhang
Computers in Biology and Medicine.2025; 187: 109763. CrossRef - Drug target therapy and emerging clinical relevance of exosomes in meningeal tumors
Swati Sharma, Rashmi Rana, Prem Prakash, Nirmal Kumar Ganguly
Molecular and Cellular Biochemistry.2024; 479(1): 127. CrossRef - The efficacy of preoperative MRI features in the diagnosis of meningioma WHO grade and brain invasion
Jun Jiang, Juan Yu, Xiajing Liu, Kan Deng, Kaichao Zhuang, Fan Lin, Liangping Luo
Frontiers in Oncology.2023;[Epub] CrossRef - The Role of Pharmacotherapy in Treatment of Meningioma: A Systematic Review
Ataollah Shahbandi, Darsh S. Shah, Caroline C. Hadley, Akash J. Patel
Cancers.2023; 15(2): 483. CrossRef - Advances in the systemic therapy for recurrent meningiomas and the challenges ahead
Yi Li, Jan Drappatz
Expert Review of Neurotherapeutics.2023; 23(11): 995. CrossRef - Clinical and pathological impact of an optimal assessment of brain invasion for grade 2 meningioma diagnosis: lessons from a series of 291 cases
Thiébaud Picart, Chloé Dumot, Jacques Guyotat, Vladislav Pavlov, Nathalie Streichenberger, Alexandre Vasiljevic, Tanguy Fenouil, Anne Durand, Emmanuel Jouanneau, François Ducray, Timothée Jacquesson, Moncef Berhouma, David Meyronet
Neurosurgical Review.2022; 45(4): 2797. CrossRef - Nomogram based on MRI can preoperatively predict brain invasion in meningioma
Jing Zhang, Yuntai Cao, Guojin Zhang, Zhiyong Zhao, Jianqing Sun, Wenyi Li, Jialiang Ren, Tao Han, Junlin Zhou, Kuntao Chen
Neurosurgical Review.2022; 45(6): 3729. CrossRef - Overexpression of Hepatocyte growth factor and its soluble receptor (s-cMet) in the serum of patients with different grades of meningioma
Farhad Mashayekhi, Soheila Talesh Sasani, Alia Saberi, Zivar Salehi
Journal of Clinical Neuroscience.2021; 93: 1. CrossRef - Brain-invasive meningiomas: molecular mechanisms and potential therapeutic options
Chaoying Qin, Meng Huang, Yimin Pan, Yuzhe Li, Wenyong Long, Qing Liu
Brain Tumor Pathology.2021; 38(3): 156. CrossRef - YAP1-FAM118B Fusion Defines a Rare Subset of Childhood and Young Adulthood Meningiomas
Kathleen M. Schieffer, Vibhuti Agarwal, Stephanie LaHaye, Katherine E. Miller, Daniel C. Koboldt, Tara Lichtenberg, Kristen Leraas, Patrick Brennan, Benjamin J. Kelly, Erin Crist, Jerome Rusin, Jonathan L. Finlay, Diana S. Osorio, Eric A. Sribnick, Jeffre
American Journal of Surgical Pathology.2021; 45(3): 329. CrossRef - Regression of Intracranial Meningiomas Following Treatment with Cabozantinib
Rupesh Kotecha, Raees Tonse, Haley Appel, Yazmin Odia, Ritesh R. Kotecha, Guilherme Rabinowits, Minesh P. Mehta
Current Oncology.2021; 28(2): 1537. CrossRef - Prognostic significance of brain invasion in meningiomas: systematic review and meta-analysis
Satoshi Nakasu, Yoko Nakasu
Brain Tumor Pathology.2021; 38(2): 81. CrossRef - Curcumin Inhibits HGF-Induced EMT by Regulating c-MET-Dependent PI3K/Akt/mTOR Signaling Pathways in Meningioma
Xiaodong Chen, Fen Tian, Peng Lun, Yugong Feng, Ho Lin
Evidence-Based Complementary and Alternative Medicine.2021; 2021: 1. CrossRef - Letter to the Editor. Preoperative seizures as predictive sign of brain invasion by meningioma
Mikhail F. Chernov
Journal of Neurosurgery.2019; 130(3): 1030. CrossRef - Investigating Trk Protein Expression between Oropharyngeal and Non-oropharyngeal Squamous Cell Carcinoma: Clinical Implications and Possible Roles of Human Papillomavirus Infection
Yoon Ah Cho, Ji Myung Chung, Hyunmi Ryu, Eun Kyung Kim, Byoung Chul Cho, Sun Och Yoon
Cancer Research and Treatment.2019; 51(3): 1052. CrossRef - Prediction of brain invasion in patients with meningiomas using preoperative magnetic resonance imaging
Alborz Adeli, Katharina Hess, Christian Mawrin, Eileen Maria Susanne Streckert, Walter Stummer, Werner Paulus, André Kemmling, Markus Holling, Walter Heindel, Rene Schmidt, Dorothee Cäcilia Spille, Peter B. Sporns, Benjamin Brokinkel
Oncotarget.2018; 9(89): 35974. CrossRef - Visceral and bone metastases of a WHO grade 2 meningioma: A case report and review of the literature
A. Paix, W. Waissi, D. Antoni, R. Adeduntan, G. Noël
Cancer/Radiothérapie.2017; 21(1): 55. CrossRef - Letter: Brain Invasion in Meningiomas—Sex-Associated Differences are not Related to Estrogen- and Progesterone Receptor Expression
Katharina Heß, Dorothee Cäcilia Spille, Andrea Wagner, Walter Stummer, Werner Paulus, Benjamin Brokinkel
Neurosurgery.2017; 81(2): E25. CrossRef - Brain invasion in meningiomas—clinical considerations and impact of neuropathological evaluation: a systematic review
Benjamin Brokinkel, Katharina Hess, Christian Mawrin
Neuro-Oncology.2017; 19(10): 1298. CrossRef - Systemic therapy for recurrent meningioma
E. Le Rhun, S. Taillibert, M. C. Chamberlain
Expert Review of Neurotherapeutics.2016; 16(8): 889. CrossRef - Brain Invasion in Meningiomas: Incidence and Correlations with Clinical Variables and Prognosis
Dorothee Cäcilia Spille, Katharina Heß, Cristina Sauerland, Nader Sanai, Walter Stummer, Werner Paulus, Benjamin Brokinkel
World Neurosurgery.2016; 93: 346. CrossRef
- MRI morphological features combined with apparent diffusion coefficient can predict brain invasion in meningioma
- Expression of c-Met Is Different along the Location and Associated with Lymph Node Metastasis of Head and Neck Carcinoma
- Ji-Young Choe, Ji Yun Yun, Soo-Jeong Nam, Ji Eun Kim
- Korean J Pathol. 2012;46(6):515-522. Published online December 26, 2012
- DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.6.515
- 7,433 View
- 50 Download
- 18 Crossref
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Abstract
PDF
Background Activation of the c-Met pathway is involved in cancer progression and the prognosis. We aimed to identify any association of c-Met protein expression with a number of clinicopathologic variables including infection of human papillomavirus and Epstein-Barr virus (EBV) in head and neck carcinomas (HNCa).
Methods Eighty-two cases were enrolled in this study. Expression of c-Met and p16 was investigated immunohistochemically. EBV was detected by
in situ hybridization and amplification of thec-Met gene by fluorescencein situ hybridization.Results The c-Met protein was expressed in 41.5% (34/82), and gene amplification was found in 1.4% (1/71). High expression of c-Met was associated with the primary location of the tumor; the hypopharynx showed the highest expression, followed by the oral cavity, larynx, and nasal cavity. Squamous cell carcinoma expressed c-Met more frequently than undifferentiated carcinoma. Also, p16 immunoreactivity or EBV infection was associated with the tumor location and well-differentiated histologic type, but were not linked to c-Met expression. The patients with positive c-Met expression showed frequent lymph node metastasis.
Conclusions Activation of the c-Met pathway might be involved in a subset of HNCa. Cases showing positive c-Met expression should be carefully monitored because of the high probability of lymph node metastasis.
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Citations
Citations to this article as recorded by- c-MET pathway in human malignancies and its targeting by natural compounds for cancer therapy
Chakrabhavi Dhananjaya Mohan, Muthu K Shanmugam, Siddegowda Gopalapura Shivanne Gowda, Arunachalam Chinnathambi, Kanchugarakoppal S. Rangappa, Gautam Sethi
Phytomedicine.2024; 128: 155379. CrossRef - Nadir paranazal sinüs kanserlerinde yeni tanımlanan reseptör tirozin kinaz mutasyonları ve potansiyel fonksiyonel etkileri
Bakiye GÖKER BAGCA, Sercan GÖDE, Göksel TURHAL, Neslihan Pınar ÖZATEŞ, Ali VERAL, Cumhur GÜNDÜZ, Çığır Biray AVCI
Ege Tıp Dergisi.2023; 62(1): 139. CrossRef - The Emerging Role of c-Met in Carcinogenesis and Clinical Implications as a Possible Therapeutic Target
Antonio Faiella, Ferdinando Riccardi, Giacomo Cartenì, Martina Chiurazzi, Livia Onofrio, Rengyun Liu
Journal of Oncology.2022; 2022: 1. CrossRef - NK4 Regulates Laryngeal Squamous Cell Carcinoma Cell Properties and Inhibits Tumorigenicity by Modulating the DKK1/Wnt/β-Catenin Axis
Shoukai Zhang, Hulai Wei, Xiaoqin Ha, Yueyu Zhang, Yufen Guo
Frontiers in Oncology.2021;[Epub] CrossRef - Epstein-Barr Virus-Associated Carcinoma of the Larynx: A Systematic Review with Meta-Analysis
Marcos Antonio Pereira de Lima, Álife Diêgo Lima Silva, Antônio Carlos Silva do Nascimento Filho, Thiago Lima Cordeiro, João Pedro de Souza Bezerra, Maria Aline Barroso Rocha, Sally de França Lacerda Pinheiro, Roberto Flávio Fontenelle Pinheiro Junior, Ma
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P. Szturz, E. Raymond, C. Abitbol, S. Albert, A. de Gramont, S. Faivre
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Petr Szturz, Marie Budíková, Jan B. Vermorken, Ivana Horová, Břetislav Gál, Eric Raymond, Armand de Gramont, Sandrine Faivre
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Levi Arnold, Jonathan Enders, Sufi Thomas
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Jung Han Kim, Bum Jun Kim, Hyeong Su Kim
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- c-MET pathway in human malignancies and its targeting by natural compounds for cancer therapy
- Expression of Hepatocyte Growth Factor/c-met by RT-PCR in Meningiomas.
- Na Rae Kim, Yang Seok Chae, Weon Jeong Lim, Seong Jin Cho
- Korean J Pathol. 2011;45(5):463-468.
- DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.463
- 3,411 View
- 29 Download
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Abstract
PDF
- BACKGROUND
Hepatocyte growth factor (HGF) is a potent mitogenic cytokine. C-met protein, which is known to be the HGF receptor has transmembrane tyrosine kinase activity and is encoded by the c-met oncogene. The HGF/c-met signaling pathway may play various roles in the carcinogenesis of various organs.
METHODS
We examined HGF and c-met mRNA expression by utilizing reverse transcription polymerase chain reaction on 40 surgically resected intracranial meningiomas (25 benign, 10 atypical, and 5 anaplastic cases).
RESULTS
An HGF overexpression was detected in 28%, 50%, and 80% of the benign, atypical and anaplastic meningiomas, respectively; a high expression of HGF or the coexpression of HGF/c-met was detected in the high grade meningiomas (the atypical and anaplastic cases, p=0.046, p=0.014). An HGF expression was statistically significant in the recurrent meningiomas (p=0.003), and HGF expression was significantly lower than c-met mRNA expression in benign meningiomas (p=0.034).
CONCLUSIONS
There was no correlation between histologic subtypes and HGF/c-met expression. Determination of HGF expression can be used as a molecular predictor for recurrence of meningioimas. These results suggest that HGF and c-met expression in meningiomas may be associated with anaplastic progression.
- The Expressions of Tyrosine Kinase Receptors, EphA2, c-met and c-erbB-2 in the Human Breast.
- Soo Kee Min, Hyun Deuk Cho, Seong Jin Cho, Hye Rim Park, Hyung Sik Shin, Young Euy Park, Bom Woo Yeom
- Korean J Pathol. 2005;39(1):15-22.
- 1,842 View
- 22 Download
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Abstract
PDF
- BACKGROUND
Tyrosine kinase receptor (TKR) is an important protein for normal-development, growth and tumorigenesis in human tissues. The purpose of this study was to evaluate the effect of TKR in the progression of breast cancer.
METHODS
The expressions of EphA2, c-met and c-erbB-2 were examined, by using immunohistochemical methods and RT-PCR, in samples of breast tissue that included 111 samples of normal epithelium, 34 samples of ductal carcinoma in situ (DCIS), and 109 samples of invasive ductal carcinomas (IDC). The results were compared with the prognostic parameters of breast cancer including the tumor grade, growth pattern, lymph node metastasis and the expressions of ER, PR, p53 and Ki-67.
RESULTS
The protein expressions of the three TKRs were higher in DCIS and IDC than in normal epithelium. The protein expression of EphA2 was correlated with a tumor grade, a labeling index of Ki-67, and the protein expression of c-met. Overexpression of c-erbB-2 was correlated with lymph node metastasis. The mRNA levels of the three TKRs were correlated with each other in normal tissue and IDC. The level of c-met mRNA was higher in the low grade tumors.
CONCLUSIONS
The three TKRs may play roles in the tumorigenesis of human breast cancer. The overexpressions of EphA2 and c-erbB-2 may be a poor prognostic parameter in breast cancers.
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