Journal of Pathology and Translational Medicine

Original Articles

Association of PTTG1 expression with invasiveness of non-functioning pituitary adenomas: Su Jung Kum, Hye Won Lee, Soon Gu Kim, Hyungsik Park, Ilseon Hwang, Sang Pyo Kim; J Pathol Transl Med. 2022;56(1):22-31. Published online October 15, 2021; DOI: https://doi.org/10.4132/jptm.2021.08.31

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Background
Pituitary tumor transforming gene 1 (PTTG1), paired-like homeodomain 2 (PITX2), and galectin-3 have been widely studied as predictive biomarkers for various tumors and are involved in tumorigenesis and tumor progression. We evaluated the usefulness of PTTG1, PITX2, and galectin-3 as predictive biomarkers for invasive non-functioning pituitary adenomas (NFPAs) by determining the relationship between the expressions of these three proteins and the invasiveness of the NFPAs. We also investigated whether PTTG1, E-cadherin, and Ki-67, which are known to be related to each other, show a correlation with NFPA features.
Methods
A retrospective study was conducted on 87 patients with NPFAs who underwent surgical removal. The NFPAs were classified into three groups based on magnetic resonance imaging findings of suprasellar extension and cavernous sinus invasion. Immunohistochemical staining for PTTG1, PITX2, galectin-3, E-cadherin, and Ki-67 was performed on tissue microarrays.
Results
PTTG1 expression showed a statistically significant correlation with the invasiveness of NFPAs, whereas PITX2 and galectin-3 did not have a relationship with the invasiveness of NFPAs. Moreover, there was no association among PTTG1, E-cadherin, and Ki-67 expression.
Conclusions
PTTG1 has the potential to serve as a predictive biomarker for invasive NFPA. Furthermore, this study may serve as a reference for the development of PTTG1-targeted therapeutic agents.

Citations

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Neoplasms and tumor-like lesions of the sellar region: imaging findings with correlation to pathology and 2021 WHO classification
Lorenzo Ugga, Raduan Ahmed Franca, Alessandra Scaravilli, Domenico Solari, Sirio Cocozza, Fabio Tortora, Luigi Maria Cavallo, Marialaura Del Basso De Caro, Andrea Elefante
Neuroradiology.2023; 65(4): 675. CrossRef
A comprehensive characterisation of phaeochromocytoma and paraganglioma tumours through histone protein profiling, DNA methylation and transcriptomic analysis genome wide
Prodromos Chatzikyriakou, Dimitria Brempou, Mark Quinn, Lauren Fishbein, Roberta Noberini, Ioannis N. Anastopoulos, Nicola Tufton, Eugenie S. Lim, Rupert Obholzer, Johnathan G. Hubbard, Mufaddal Moonim, Tiziana Bonaldi, Katherine L. Nathanson, Louise Izat
Clinical Epigenetics.2023;[Epub] CrossRef
Expression and clinical significance of Cathepsin K and MMPs in invasive non-functioning pituitary adenomas
Hongyan Liu, Saichun Zhang, Ting Wu, Zhaohui Lv, Jianming Ba, Weijun Gu, Yiming Mu
Frontiers in Oncology.2022;[Epub] CrossRef

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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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

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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
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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
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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
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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
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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
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p53 Expression and Ki-67 Labeling Index in Brain Tumor with Special Reference to Tumor and Histologic Grade.: Duck Hwan Kim, Yeon Lim Suh, Dong Ik Shin, Hyung Jin Shin, Jong Hyun Kim; Korean J Pathol. 1998;32(2):81-87.

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Abstract PDF: Mutation in the p53 suppressor gene is the most common genetic alteration found in human cancers including primary brain tumors. Ki-67 labeling index(LI) is known to be a marker of proliferating activity. The purpose of this study was to verify whether an immunohistochemical expression of p53 antibody and Ki-67 LI could be related to different clinicopathologic parameters including histologic grade, size, invasiveness and recurrence of the brain tumors. Materials were based on the 147 surgically resected brain tumors during the last two years. Of the 147 brain tumors, there were 35 astrocytic tumors, 35 meningiomas, 10 oligodendrogliomas, 7 craniopharyngiomas, 5 dysembryoplastic neuroepithelial tumors, 4 medulloblastomas, 5 ependymomas, 23 pituitary adenomas, 9 schwannomas, and 14 other brain tumors. The p53 expression and Ki-67 LI were higher in malignant brain tumors including astrocytic tumors, medulloblastoma, PNET and gliosarcoma. The p53 positivity was correlated with histologic grades and tumor recurrence. The brain tumors with a high Ki-67 LI(>6%) also showed a close relationship to a higher histologic grading, radiological invasiveness and recurrence. There was no evident correlation with the age and tumor size with p53 expression and Ki-67 LI. These results suggest that p53 overexpression and high proliferation potential of the tumor cells are associated with the higher histologic grade and aggressive clinical course in the central nervous system tumors.

Expression of Matrix Metalloproteinase-2 and -9 in Oral Squamous Cell Carcinomas in Relation to the Histologic Invasiveness and Cellular Differentiation.: Seong Doo Hong, San Pyo Hong, Yong Sik Kim, Jae Il Lee, Chang Yun Lim; Korean J Pathol. 1999;33(4):243-250.

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Abstract PDF: A poor prognosis of oral squamous cell carcinoma (SCC) is partly due to the invasiveness and metastasis of the tumor. A key element in tumor invasion and metastasis in the degradation of extracellular matrix is matrix metalloproteinases (MMPs). This study was performed to determine the expression of MMP-2 and MMP-9 of oral SCCs with regard to the histologic invasiveness and differentiation in 5 normal oral mucosa and 36 oral SCCs. The histologic invasiveness of oral SCCs were classified into 4 grades. The differentiation of oral SCCs was divided into 3 grades. The streptavidin-biotin immunohistochemical staining, using MMP-2 and MMP-9 monoclonal antibodies, was performed to determine the expression of MMP-2 and MMP-9. The expression of MMP-2 was positive in 6 of 17 oral SCCs with weak invasiveness and was positive in 7 of 19 oral SCCs with strong invasiveness. The MMP-2 expression did not increase significantly with respect to the invasiveness of oral SCCs (P>0.05). The expression of MMP-9 was strongly positive in 6 out of 17 SCCs with weak invasiveness and was strongly positive in 14 of 19 SCCs with strong invasiveness. The MMP-9 expression increased significantly with respect to the invasiveness of oral SCCs; the stronger the expression, the stronger the invasiveness (P<0.05). The expression of MMP-9 was in 57.9% of well differentiated SCCs, 57.1% of moderately differentiated ones, and 33.3% of poorly differentiated SCCs. The expression of MMP-2 and MMP-9 did not increase significantly with respect to the histologic differentiation. We conclude that with respect to the invasiveness, the MMP-9 expression increases significantly in oral SCCs but the MMP-2 expression does not; and that with respect to the histologic differentiation, their expressions do not increase significantly. These results suggeste that MMP-9 can be used as a tool to evaluate the invasiveness of oral SCCs.

Study on the Function of NAG-1 in Hepatocellular and Gastric Carcinoma Cells.: Tae Jung Jang; Korean J Pathol. 2007;41(4):244-251.

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Abstract PDF: BACKGROUND
Nonsteroidal anti-inflammatory drug activated gene (NAG-1) has proapoptotic activities in the colon and also in gastric cancer cells that lack any endogenous COX-2 expression. Recent studies have suggested that the proa- poptotic activity of NAG-1 is cell type specific. I investigated the cell proliferation, invasiveness and apoptosis in Hep3B cells and SNU719 cells by determining the different expression levels of NAG-1. In addition, I examined the gene profile in the Hep3B cells that have a stable expression of NAG-1.
METHODS
SNU719 cells and several clones of Hep3B cells with a stable expression of NAG-1 were used. I reduced the expression level of NAG-1 via the RNAi method. An Agilent Human 22k microarray was used for studying the gene profile in Hep3B cells that had a stable expression of NAG-1.
RESULTS
The expression level of NAG-1 did not influence apoptosis, cell proliferation and invasiveness in Hep3B cells. There was no correlation between the reduction of the endogenous NAG-1 expression and cell proliferation, including invasiveness, in the SNU719 cells. However, a knocked-down NAG-1 expression protected against apoptosis in the SNU719 cells. The microarray analysis results showed that 0.25% (58/22,575) of the genes were induced or repressed more than three fold in the Hep3B cells that had a stable expression of NAG-1.
CONCLUSIONS
Proapoptotic activity of NAG-1 is found in gastric cancer cells, but not in hepatocellular cancer cells.

Differential Expression of CD34 and Smooth Muscle Actin in the Stroma of Small Lung Adenocarcinoma with Mixed Bronchioloalveolar and Invasive Components.: Mee Sook Roh, Jong Woo Choi, Hyoun Wook Lee, Hyuk Chan Kwon, Tae Ho Park, Phil Jo Choi, Chang Hun Lee, Bong Kwon Cheon; Korean J Pathol. 2005;39(3):158-163.

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Abstract PDF: BACKGROUND
Absence of CD34-positive fibroblasts was reported within the stroma associated with invasive carcinomas. Conversely, tumor-associated desmoplastic stroma is characterized by the presence of smooth muscle actin (SMA)-reactive myofibroblasts. The present study was undertaken in order to elucidate whether the different distributions of stromal CD34-positive fibroblasts and SMA-reactive myofibroblasts are sensitive or specific markers of tumor invasion in small lung adenocarcinomas.
METHODS
Immunohistochemical stainings for CD34 and SMA were done in 37 peripheral adenocarcinomas less than 3.0 cm in diameter, including 16 adenocarcinomas with bronchioloalveolar carcinoma (BAC) and invasive components (mixed), and 21 invasive adenocarcinomas without BAC components (invasive).
RESULTS
The fibroblasts within the BAC components of the mixed group were mainly CD34-positive (81.2%) and preferentially SMA-negative (56.3%). In contrast, the fibroblasts within the invasive components of the mixed group were mainly CD34-negative (75.0%) and SMApositive (87.5%). The stromal cells of the invasive group were mostly negative for CD34 (90.5%) and positive for SMA (95.3%).
CONCLUSIONS
The loss of CD34 and the acquisition of SMA in the stromal cells within the tumor were related to tumor invasion (p<0.05). Thus, expression patterns of CD34 and SMA can be used to detect small foci of early stromal invasion in adenocarcinomas of the lung.

CD24 Expression in Gastric Adenocarcinoma Is Associated with Tumor Invasiveness.: Kyeong Cheon Jung, Jae Nam Seo, Tae Woon Kim, Young Mi Choi, Kwon Ik Oh, Hun Ho Song, Hyung Sik Shin, Young Euy Park; Korean J Pathol. 2004;38(6):388-393.

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Abstract PDF: BACKGROUND
CD24, also referred to as the heat stable antigen in mice, is a glycosyl phosphatidylinositol- linked glycoprotein expressed by thymocytes, B cells, neutrophils and immature neuronal cells. It has been recently observed in a variety of human malignancy. Here, we demonstrated the expression of CD24 in gastric adenocarcinomas.
METHODS
A total of 40 gastric adenocarcinomas and 20 tubular adenomas were immunohistochemically examined for the expression of CD24 and matrix metalloproteinase-2 (MMP-2) proteins. The immunoreactivity of CD24 was semiquantitatively scored (0, 1+, 2+) and compared with clinicopathologic variables and MMP-2 expression in tumor cells.
RESULTS
CD24 was rarely expressed in normal gastric tissue and not expressed in tubular adenoma. In contrast, a moderate/strong expression (2+) of CD24 was observed in 25% of gastric adenocarcinomas, and 30% cases showed a weak CD24 staining (1+). Moreover, CD24 expression was significantly correlated with the depth of tumor invasion and MMP-2 expression.
CONCLUSION
These results suggest that the aberrant expression of CD24 in gastric adenocarcinomas might be associated with tumor progression and invasiveness.

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