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

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Jun Jiang, Juan Yu, Xiajing Liu, Kan Deng, Kaichao Zhuang, Fan Lin, Liangping Luo
Frontiers in Oncology.2023;[Epub] CrossRef
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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
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Nomogram based on MRI can preoperatively predict brain invasion in meningioma
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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
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Systemic therapy for recurrent meningioma
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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
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Effects of Fixation and Storage of Human Tissue Samples on Nucleic Acid Preservation: Soo Kyung Nam, Joon Im, Yoonjin Kwak, Nayoung Han, Kyung Han Nam, An Na Seo, Hye Seung Lee; Korean J Pathol. 2014;48(1):36-42. Published online February 25, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.1.36

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Abstract PDF

Background

Because of recent advances in the molecular diagnosis of cancer patients, tissue quality has become more important in daily practice.

Methods

To evaluate the effects of fixative, duration of fixation, decalcification, and storage periods on nucleic acid integrity, DNA and RNA were extracted from gastrointestinal cancer tissue. The yield and purity were analyzed, and polymerase chain reaction (PCR) for glyceraldehyde 3-phosphate dehydrogenase (GAPDH; 60 bp), β-actin (148 bp), and human growth hormone (hGH; 434 bp) and real-time reverse transcription-PCR for β-actin (97 bp) were performed.

Results

All formalin-fixed paraffin-embedded (FFPE) and methacarn-fixed paraffin-embedded (MFPE) samples tested positive for GAPDH and β-actin by PCR. hGH was successfully detected in all MFPE samples, but in only 46.7% of the FFPE samples. Prolonged formalin fixation resulted in fewer GAPDH and β-actin PCR products, and amplification of hGH was not successful. The PCR and reverse transcription-PCR results were significantly affected by the duration of decalcification. The yield, purity, and integrity of mRNA progressively decreased with increased storage periods of paraffin blocks.

Conclusions

Fixation and storage should therefore be standardized in order to improve the quality of molecular pathologic diagnosis.

Citations

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Immunohistochemical Classification of Primary and Secondary Glioblastomas: Kyu Sang Lee, Gheeyoung Choe, Kyung Han Nam, An Na Seo, Sumi Yun, Kyung Ju Kim, Hwa Jin Cho, Sung Hye Park; Korean J Pathol. 2013;47(6):541-548. Published online December 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.6.541

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Abstract PDF

Background

Glioblastomas may develop de novo (primary glioblastomas, P-GBLs) or through progression from lower-grade astrocytomas (secondary glioblastomas, S-GBLs). The aim of this study was to compare the immunohistochemical classification of glioblastomas with clinically determined P-GBLs and S-GBLs to identify the best combination of antibodies for immunohistochemical classification.

Methods

We evaluated the immunohistochemical expression of epidermal growth factor receptor (EGFR), p53, and isocitrate dehydrogenase 1 (IDH-1) in 150 glioblastoma cases.

Results

According to clinical history, the glioblastomas analyzed in this study consisted of 146 P-GBLs and 4 S-GBLs. Immunohistochemical expression of EGFR, p53, and IDH-1 was observed in 62.6%, 49.3%, and 11.1%, respectively. Immunohistochemical profiles of EGFR(+)/p53(-), IDH-1(-)/EGFR(+)/p53(-), and EGFR(-)/p53(+) were noted in 41.3%, 40.2%, and 28.7%, respectively. Expression of IDH-1 and EGFR(-)/p53(+) was positively correlated with young age. The typical immunohistochemical features of S-GBLs comprised IDH-1(+)/EGFR(-)/p53(+), and were noted in 3.6% of clinically P-GBLs. The combination of IDH-1(-) or EGFR(+) was the best set of immunohistochemical stains for identifying P-GBLs, whereas the combination of IDH-1(+) and EGFR(-) was best for identifying S-GBLs.

Conclusions

We recommend a combination of IDH-1 and EGFR for immunohistochemical classification of glioblastomas. We expect our results to be useful for determining treatment strategies for glioblastoma patients.

Citations

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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.

Citations

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Giovanni Maria Iannantuono, Silvia Riondino, Stefano Sganga, Mario Roselli, Francesco Torino
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ESC, ALK, HOT and LOT: Three Letter Acronyms of Emerging Renal Entities Knocking on the Door of the WHO Classification
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ALK-rearranged renal cell carcinoma with a novel PLEKHA7-ALK translocation and metanephric adenoma-like morphology
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Characteristics of Renal Cell Carcinoma Harboring TPM3-ALK Fusion
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Lack of expression of ALK and CD30 in breast carcinoma by immunohistochemistry irrespective of tumor characteristics
Samer Nassif, Ziad M. El-Zaatari, Michel Attieh, Maya Hijazi, Najla Fakhreddin, Tarek Aridi, Fouad Boulos
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Xiao-tong Wang, Ru Fang, Sheng-bing Ye, Ru-song Zhang, Rui Li, Xuan Wang, Rong-hao Ji, Zhen-feng Lu, Heng-hui Ma, Xiao-jun Zhou, Qiu-yuan Xia, Qiu Rao
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Adam Gorczynski, Piotr Czapiewski, Aleksandra Korwat, Lukasz Budynko, Monika Prelowska, Krzysztof Okon, Wojciech Biernat
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ALK-TPM3 rearrangement in adult renal cell carcinoma: a case report and literature review
Jing Yang, Lei Dong, Hong Du, Xiu-bo Li, Yan-xiao Liang, Guo-rong Liu
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Reza Alaghehbandan, Delia Perez Montiel, Ana Silvia Luis, Ondrej Hes
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ALK-TPM3 rearrangement in adult renal cell carcinoma: Report of a new case showing loss of chromosome 3 and literature review
Yohan Bodokh, Damien Ambrosetti, Valérie Kubiniek, Branwel Tibi, Matthieu Durand, Jean Amiel, Morgane Pertuit, Anne Barlier, Florence Pedeutour
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BMC Cancer.2018;[Epub] CrossRef
Responses to Alectinib in ALK-rearranged Papillary Renal Cell Carcinoma
Sumanta K. Pal, Paulo Bergerot, Nazli Dizman, Cristiane Bergerot, Jacob Adashek, Russell Madison, Jon H. Chung, Siraj M. Ali, Jeremy O. Jones, Ravi Salgia
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Genetic analysis and clinicopathological features of ALK‐rearranged renal cell carcinoma in a large series of resected Chinese renal cell carcinoma patients and literature review
Wenjuan Yu, Yuewei Wang, Yanxia Jiang, Wei Zhang, Yujun Li
Histopathology.2017; 71(1): 53. CrossRef
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Yuzo Oyama, Haruto Nishida, Takahiro Kusaba, Hiroko Kadowaki, Motoki Arakane, Tsutomu Daa, Dai Watanabe, Yasuyuki Akita, Fuminori Sato, Hiromitsu Mimata, Shigeo Yokoyama
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New and emerging renal tumour entities
Naoto Kuroda, Ondřej Hess, Ming Zhou
Diagnostic Histopathology.2016; 22(2): 47. CrossRef
ALK‐rearranged renal cell carcinomas in children
Mariana M. Cajaiba, Lawrence J. Jennings, Stephen M. Rohan, Antonio R. Perez‐Atayde, Adrian Marino‐Enriquez, Jonathan A. Fletcher, James I. Geller, Katrin M. C. Leuer, Julia A. Bridge, Elizabeth J. Perlman
Genes, Chromosomes and Cancer.2016; 55(5): 442. CrossRef
Two Cases of Renal Cell Carcinoma Harboring a Novel STRN-ALK Fusion Gene
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Expanding the spectrum of ALK‐rearranged renal cell carcinomas in children: Identification of a novel HOOK1‐ALK fusion transcript
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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.

Citations

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Sarcomatoid and Rhabdoid Renal Cell Carcinoma
Adebowale J. Adeniran, Brian Shuch, Peter A. Humphrey
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Harrison C. Gottlich, Reza Nabavizadeh, Mihai Dumbrava, Rodrigo Rodrigues Pessoa, Ahmed M. Mahmoud, Ishita Garg, Jacob Orme, Brian A. Costello, John Cheville, Fabrice Lucien
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Painful, bleeding fingertip papule
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Development and initial clinical testing of a multiplexed circulating tumor cell assay in patients with clear cell renal cell carcinoma
Rory M. Bade, Jennifer L. Schehr, Hamid Emamekhoo, Benjamin K. Gibbs, Tamara S. Rodems, Matthew C. Mannino, Joshua A. Desotelle, Erika Heninger, Charlotte N. Stahlfeld, Jamie M. Sperger, Anupama Singh, Serena K. Wolfe, David J. Niles, Waddah Arafat, John
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Laparoscopic cytoreductive nephrectomy and adrenalectomy for metachronous RCC metastases—Case report
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Does CARMENA mark the end of cytoreductive nephrectomy for metastatic renal cell carcinoma?
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Cheol Lee, Bohyun Kim, Boram Song, Kyung Chul Moon
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Sarah P. Psutka, John C. Cheville, Brian A. Costello, Suzanne B. Stewart-Merrill, Christine M. Lohse, Bradley C. Leibovich, Stephen A. Boorjian, R. Houston Thompson
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Cyclooxygenase-2 Expression and Its Prognostic Significance in Clear Cell Renal Cell Carcinoma: Ji Won Lee, Jeong Hwan Park, Ja Hee Suh, Kyung Han Nam, Ji-Young Choe, Hae Yoen Jung, Ji Yoen Chae, Kyung Chul Moon; Korean J Pathol. 2012;46(3):237-245. Published online June 22, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.3.237

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Abstract PDF

Background

The prognostic value of cyclooxygenase-2 (COX-2) in human renal cell carcinoma (RCC) remains unclear. The purposes of this study are to elucidate the clinical significance of COX-2 in clear cell RCC (CCRCC) and to assess the treatment effect of COX-2 inhibition on CCRCC cell lines.

Methods

Using tumor samples obtained from 137 patients who had undergone nephrectomy at Seoul National University Hospital, we evaluated COX-2 expression on immunohistochemistry. Moreover, we performed the cell proliferation assay using 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) and cell invasion assay. Thus, we evaluated the effect of meloxicam, an inhibitor of COX-2, in two human CCRCC cell lines.

Results

Cancer-specific survival (p=0.038) and progression-free survival (p=0.031) were shorter in the COX-2 high expression group. A multivariate logistic regression model showed that COX-2 expression was an independent risk factor for pTNM stage and Fuhrman nuclear grade. The MTT assay revealed that COX-2 inhibition led to the suppression of the proliferation of CCRCC cell lines. Moreover, it also reduced their invasion capacity.

Conclusions

This study postulates that COX-2 is a poor prognostic indicator in human CCRCC, suggesting that COX-2 inhibition can be a potential therapy in CCRCC.

Citations

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Free-fatty acid receptor-1 (FFA1/GPR40) promotes papillary RCC proliferation and tumor growth via Src/PI3K/AKT/NF-κB but suppresses migration by inhibition of EGFR, ERK1/2, STAT3 and EMT
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Markers for Screening Lynch Syndrome Are Reliable and Useful for Identifying the Specimen Mislabeling: Sun-ju Byeon, Jiwoon Choi, Kyung Han Nam, Bo-Gun Jang, Hee Eun Lee, Min A Kim, Woo Ho Kim; Korean J Pathol. 2012;46(2):131-136. Published online April 25, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.2.131

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Abstract PDF

Background

During specimen processing in surgical pathology laboratories, specimen-related adverse events (SRAEs), such as mislabeling and specimen mixed-up might occur. In these situations, molecular techniques using short tandem repeat (STR) loci are required to identify the personal identity. Microsatellite instability (MSI) test is widely used for screening the hereditary non-polyposis colon cancer (Lynch syndrome) in surgical pathologies using polymorphic STR markers. We tried to evaluate the applicability of the MSI test for SRAEs.

Methods

We obtained 253 MSI test results to analyze the allele frequencies. After calibrating the estimated nucleotide lengths, we calculated the allele frequencies, a random match probability, and a likelihood ratio (LR) of three dinucleotide STR markers (D5S349, D17S250, and D2S123).

Results

The distribution of LR was 136.38 to 5,606,213.10. There was no case of LR<100. In addition, there were 153 cases (60.5%) of LR ranging from 100 to 10,000 and 100 cases (39.5%) of LR>10,000. Furthermore, the combined probability of identity was 9.23×10^-4 and the combined power of exclusion was 0.99908.

Conclusions

Using the three STR markers that are recommended for MSI test, all the cases were positively identified in 1% range and about one-third cases showed high LR (>10,000). These results showed that MSI tests are useful to screen the personal identity in case of SRAE in pathology laboratories.

Citations

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