Journal of Pathology and Translational Medicine

Original Articles

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

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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

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

Clinicopathological Analysis of Hepatocellular Adenoma According to New Bordeaux Classification: Report of Eight Korean Cases: Hyunchul Kim, Ja-June Jang, Dong-Sik Kim, Beom Woo Yeom, Nam Hee Won; Korean J Pathol. 2013;47(5):411-417. Published online October 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.5.411

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Abstract PDF

Background

Hepatocellular adenoma (HCA) is a rare benign tumor of the liver. A subtype classification of HCA (hepatocyte nuclear factor 1α [HNF1α]-mutated, β-catenin-mutated HCA, inflammatory HCA, and unclassified HCA) has recently been established based on a single institutional review of a HCA series by the Bordeaux group.

Methods

We used histologic and immunohistochemical parameters to classify and evaluate eight cases from our institution. We evaluated the new classification method and analyzed correlations between our results and those of other reports.

Results

Seven of our eight cases showed histologic and immunohistochemical results consistent with previous reports. However, one case showed overlapping histologic features, as previously described by the Bordeaux group. Four cases showed glutamine synthetase immunohistochemical staining inconsistent with their classification, indicating that glutamine synthetase staining may not be diagnostic for β-catenin-mutated HCA. HNF1α-mutated HCA may be indicated by the absence of liver fatty acid binding protein expression. Detection of amyloid A may indicate inflammatory HCA. HCA with no mutation in the HNF1α or β-catenin genes and no inflammatory protein expression is categorized as unclassified HCA.

Conclusions

Although the new classification is now generally accepted, validation through follow-up studies is necessary.

Citations

Citations to this article as recorded by

Relevance of morphological features for hepatocellular adenoma classification in pathology practice
Carla Henriques Agostini, Osmar Damasceno Ribeiro, Arlete Fernandes, Adriana Caroli-Bottino, Vera Lucia Pannain
Surgical and Experimental Pathology.2020;[Epub] CrossRef
The molecular functions of hepatocyte nuclear factors – In and beyond the liver
Hwee Hui Lau, Natasha Hui Jin Ng, Larry Sai Weng Loo, Joanita Binte Jasmen, Adrian Kee Keong Teo
Journal of Hepatology.2018; 68(5): 1033. CrossRef
Hepatocellular adenoma: Classification, variants and clinical relevance
Paulette Bioulac-Sage, Christine Sempoux, Charles Balabaud
Seminars in Diagnostic Pathology.2017; 34(2): 112. CrossRef
A Limited Immunohistochemical Panel Can Subtype Hepatocellular Adenomas for Routine Practice
Brent K. Larson, Maha Guindi
American Journal of Clinical Pathology.2017; 147(6): 557. CrossRef
Hepatocellular Neoplasms Arising in Association With Androgen Use
Sounak Gupta, Bita V. Naini, Richard Munoz, Rondell P. Graham, Benjamin R. Kipp, Michael S. Torbenson, Taofic Mounajjed
American Journal of Surgical Pathology.2016; 40(4): 454. CrossRef
Pigmented hepatocellular adenomas have a high risk of atypia and malignancy
Taofic Mounajjed, Saba Yasir, Patrice A Aleff, Michael S Torbenson
Modern Pathology.2015; 28(9): 1265. CrossRef

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

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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.

Immunohistochemical Study about the Origin of Bile Ductules Proliferation in Obstructive Liver Disease.: Hyun Jung Sung, Byung Chul Ann, Jae Tae Lee, Yoon Seup Kum, Jae Bok Park, Kwan Kyu Park; Korean J Pathol. 2009;43(2):126-132.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.2.126

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Abstract PDF: BACKGROUND
The relationship between bile duct proliferation and portal fibrosis in obstructive liver diseases remains unclear. The purpose of this study is to analyze the relationship between hepatic stellate cells (HSC), hepatocytes and bile ductule proliferation in obstructive liver disease using immunoreactivity for alpha-SMA (alpha-smooth muscle actin), CK7, and CK19.
METHODS
We used 20 human tissue samples with hepatic fibrosis due to intrahepatic stones and liver cirrhosis. Immunohistochemical staining was performed using the streptavidin-biotin method.
RESULTS
Proliferations of bile ductules at the periphery of the hepatic lobules, and diffuse HSC activation in the perisinusoidal spaces were observed in all cases. Immunoreactivity of the hepatocytes for CK7 and CK19 suggested a possible phenotypic transformation into bile duct epithelium during fibrogenesis. Immunohistochemical-analyses of alpha-SMA expression profiles showed that intralobular HSCs and some hepatocytes underwent early phenotypic changes, and that the accumulation of collagen coincides with that of alpha-SMA-labeled myofibroblasts around portal/septal ductular structures.
CONCLUSIONS
Our results showed the possibility of a phenotypic transformation of hepatocytes into bile ductular epithelium. It is suggested that hepatocytes might play a role in bile ductule proliferation in obstructive liver disease.

Expression of Met Protein in Colorectal Carcinoma.: Kyung Un Choi, Jin Sook Lee, Chang Hun Lee, Mee Young Sol, Kang Suk Suh; Korean J Pathol. 2000;34(7):501-508.

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Abstract PDF: Met protein is a transmembrane 190 kD heterodimer with tyrosine kinase activity, encoded by c-Met oncogene. It serves as a high affinity receptor for hepatocyte growth factor (HGF)/scatter factor (SF), a cytokine which stimulates cell proliferation, motility, and invasion. In this study, we immunohistochemically evaluated the expression of Met/hepatocyte growth factor receptor in colorectal cancers. Met protein was expressed in 31 of 72 patients (43.1%). The staining pattern was cytoplasmic in nature, present throughout the tumor, and showed variable intensity from case to case. The relationship between the expression rate and intensity, and age and sex of patients, tumor size (p=0.645), tumor site (p=0.902) and tumor differentiation (p=0.844) was not statistically significant. The expression rate and intensity were significantly correlated with lymphovascular invasion (p=0.001), lymph node metastasis (p=0.010), depth of invasion (0.019), and stage (p=0.023). Cytoplasmic accumulation of Met protein was not associated with enhanced PCNA index of tumor cells (p=0.052). These results suggest that Met protein may play an important role in the invasion and metastasis of colorectal cancer cells.

Analysis of DNA Ploidy Patterns and Nuclear Morphometry in Diethylnitrosamine Induced Hepatocyte Nodules and Hepatocellular Carcinoma of Rats.: Chan Choi, Myung Kwan Kim, Kwan Mook Chae, Eun Cheol Kim, Hyung Bae Moon; Korean J Pathol. 1993;27(3):226-234.

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Abstract PDF: This study was designed to answer the question; (1) How does the DNA ploidy pattern change in hepatocarcinogenesis? (2) How does the nuclear morphology change in hepatocarcinogenesis? Diethylnitrosamine(DEN) (16.5 mg per kg) was subcutaneously injected to female Sprague-Dawley rats(150~200g) by weekly interval for 30 weeks. DNA ploidy and parameters of nuclear morphology were measured by image analyser(IBAS 200, Kontron, FRG). The DNA ploidy pattern was divided into three basic patterns(diploid, polyploid, and aneuploid modes). In 8 cases of saline-injected control rats, the DNA histograms showed all polyploid pattern. Inhepatocyte nodules(hyperplastic nodules), DNA diploidy was the most frequent pattern, being followed by polyploid and aneuploid DNA patterns, contrast to hepatocelular carcinomas in which polyploid DNA pattern was most frequently noted being followed by diploid and aneuploid DNA pattern. Although the nuclei of hepatocytes in hepatocyte nodules and hepatocellular carcinomas were larger and more pleomorphic than those of normal hepatocytes, they were as same as those of normal hepatocytes in regard to nuclear hyperchromasia. DNA content, which was increased in hepatocarcinogenesis, was significantly related to the nuclear area.

Biologic Significance of Hepatocyte Hepatitis B Core Antigen Expression in Chronic Hepatitis B Virus Infection.: Hye Kung Lee, Sang Ho Kim; Korean J Pathol. 1989;23(3):287-291.

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Abstract PDF: To elucidate the biologic significause of hepatocyte B core antigen (HBcAg) expression and its relation to the natural course of hepatitis B virus (HBV) infection, we tried to correlate the patterns of HBcAg with the HBV replication state and with disease activity in 40 needle biopsies performed on hepatitis B surface antigen (HBsAg) carriers aged from 15 to 46 years. In 32 of 40 cases, HBcAg was present in the hepatocyte nucleus (nHBcAg), in the cytoplams (cHBcAg) or in both (mixed). Pure nHBcAg was seen only in minimal hepatitis, but a diffuse pattern of expression of cytoplasmic HBcAg and mixed cytoplasmic and nuclear expression of HBcAg were seen in active hepatitis. There was also a good correlation between liver HBcAg and serum HBeAg.
Case
s in which HBcAg expression were observed were positive for serum HBeAg (81%) and the cases negative for HBcAg were all positive for serum anti-HBe.

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