Journal of Pathology and Translational Medicine

Original Articles

Characteristics of RET gene mutations in Vietnamese medullary thyroid carcinoma patients: a single-center analysis: Van Hung Pham, Quoc Thang Pham, Minh Nguyen, Hoa Nhat Ngo, Thao Thi Thu Luu, Nha Dao Thi Minh, Trâm Đặng, Anh Tu Thai, Hoang Anh Vu, Dat Quoc Ngo; J Pathol Transl Med. 2025;59(2):125-132. Published online March 14, 2025; DOI: https://doi.org/10.4132/jptm.2025.01.18

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Abstract PDF Supplementary Material: Background
The RET gene point mutation is the main molecular alteration involved in medullary thyroid carcinoma (MTC) tumorigenesis. Previous studies in Vietnam mainly consisted of case reports, with limited data on larger sample sizes. In this study, we investigated RET gene mutations in exons 10, 11, and 16 and analyzed clinicopathological features of a series of Vietnamese MTC patients. Methods: We collected 33 tissue samples from patients with MTC and analyzed RET mutations using the Sanger sequencing method. The relationship between hotspot RET mutations (exons 10, 11, 16) and clinicopathological features were investigated. Results: Among the 33 analyzed cases, 17 tumors (52%) harbored RET mutations in exon 10, 11, or 16. A total of 10 distinct genetic alterations were identified, including eight missense mutations and two short indels. Of these, seven were classified as pathogenic mutations based on previous publications, with p.M918T being the most frequent (4 cases), followed by p.C634R (3 cases) and p.C618R (3 cases). Mutations were significantly associated with specific histological patterns, such as the nested/insular pattern (p=.026), giant cells (p=.007), nuclear pleomorphism (p=.018), stippled chromatin (p=.044), and amyloid deposits (p=.024). No mutations were found in germline analyses, suggesting these were somatic alterations. Conclusions: Our results provided the first comprehensive analysis of RET mutations in Vietnamese MTC patients. The most frequent mutation was p.M918T, followed by p.C634R and p.C618R. Mutations in these three exons were linked to specific histopathological features. Information on mutational profiles of patients with MTC will further aid in the development of targeted therapeutics to ensure effective disease management.

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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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.

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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

PLAG1, SOX10, and Myb Expression in Benign and Malignant Salivary Gland Neoplasms: Ji Hyun Lee, Hye Ju Kang, Chong Woo Yoo, Weon Seo Park, Jun Sun Ryu, Yuh-Seog Jung, Sung Weon Choi, Joo Yong Park, Nayoung Han; J Pathol Transl Med. 2019;53(1):23-30. Published online November 14, 2018; DOI: https://doi.org/10.4132/jptm.2018.10.12

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Abstract PDF

Background
Recent findings in molecular pathology suggest that genetic translocation and/oroverexpression of oncoproteins is important in salivary gland tumorigenesis and diagnosis. Weinvestigated PLAG1, SOX10, and Myb protein expression in various salivary gland neoplasm tissues.
Methods
A total of 113 cases of surgically resected salivary gland neoplasms at the NationalCancer Center from January 2007 to March 2017 were identified. Immunohistochemical stainingof PLAG1, SOX10, and Myb in tissue samples was performed using tissue microarrays.
Results
Among the 113 cases, 82 (72.6%) were benign and 31 (27.4%) were malignant. PLAG1 showednuclear staining and normal parotid gland was not stained. Among 48 cases of pleomorphicadenoma, 29 (60.4%) were positive for PLAG1. All other benign and malignant salivary glandneoplasms were PLAG1-negative. SOX10 showed nuclear staining. In normal salivary gland tissuesSOX10 was expressed in cells of acinus and intercalated ducts. In benign tumors, SOX10 expressionwas observed in all pleomorphic adenoma (48/48), and basal cell adenoma (3/3), but not inother benign tumors. SOX10 positivity was observed in nine of 31 (29.0%) malignant tumors.Myb showed nuclear staining but was not detected in normal parotid glands. Four of 31 (12.9%)malignant tumors showed Myb positivity: three adenoid cystic carcinomas (AdCC) and onemyoepithelial carcinoma with focal AdCC-like histology.
Conclusions
PLAG1 expression is specificto pleomorphic adenoma. SOX10 expression is helpful to rule out excretory duct origin tumor,but its diagnostic value is relatively low. Myb is useful for diagnosing AdCC when histology isunclear in the surgical specimen.

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Head and Neck Pathology.2023; 17(3): 864. CrossRef
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Journal of Clinical Pathology.2023; 76(10): 649. CrossRef
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Malak Mohammed AlOsaimi, Abdulaziz Mohammed AlSubaheen, Taif Saleh Jameel, Rand Abdulrahman AlSalamah, Dalal Naseh AlAnzi, Norah Ameen AlOushan, Fahad Fadhel AlShammari, Cristalle Soman
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Current Issues in Molecular Biology.2023; 45(12): 10131. CrossRef
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American Journal of Clinical Pathology.2022; 157(1): 98. CrossRef
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Case Study

Abrupt Dyskeratotic and Squamoid Cells in Poorly Differentiated Carcinoma: Case Study of Two Thoracic NUT Midline Carcinomas with Cytohistologic Correlation: Taebum Lee, Sangjoon Choi, Joungho Han, Yoon-La Choi, Kyungjong Lee; J Pathol Transl Med. 2018;52(5):349-353. Published online July 27, 2018; DOI: https://doi.org/10.4132/jptm.2018.07.16

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Abstract PDF

Cytologic diagnosis of nuclear protein in testis (NUT) midline carcinoma (NMC) is important due to its aggressive behavior and miserable prognosis. Early diagnosis of NMC can facilitate proper management, and here we report two rare cases of thoracic NMC with cytohistologic correlation. In aspiration cytology, the tumor presented with mixed cohesive clusters and dispersed single cells, diffuse background necrosis and many neutrophils. Most of the tumor cells had scanty cytoplasm and medium-sized irregular nuclei, which had fine to granular nuclear chromatin. Interestingly, a few dyskeratotic cells or squamoid cell clusters were present in each case. Biopsy specimen histology revealed more frequent squamous differentiation, and additional immunohistochemistry tests showed nuclear expression of NUT. Because this tumor has a notorious progression and has been previously underestimated in terms of its prevalence, awareness of characteristic findings and proper ancillary tests should be considered in all suspicious cases.

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Diagnostic significance and cytological features of NUT carcinoma by EBUS‐FNA, a case report and literature review
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Cytopathology.2024; 35(4): 497. CrossRef
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Crystal Y. Li, Salih Salihoglu, Francisco J. Civantos, Jaylou M. Velez Torres
Diagnostic Cytopathology.2024;[Epub] CrossRef
Nuclear Protein in Testis (NUT) Carcinoma: A Comprehensive Immunohistochemical Analysis of 57 Cases With Consideration of Interpretation and Pitfall Recognition
Ayesha Farooq, Allison L. Kerper, Jennifer M. Boland, Ying-Chun Lo
Archives of Pathology & Laboratory Medicine.2024; 148(8): 898. CrossRef
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Sameer Chhetri Aryal, Shereen Zia, Shannon Rodgers, Yulei Shen, Kyle Perry, Lisi Yuan
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Ayae Saiki, Keita Sakamoto, Yuan Bee, Takehiro Izumo
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Frontiers in Oncology.2022;[Epub] CrossRef
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Rimlee Dutta, Aruna Nambirajan, Saurabh Mittal, Sinchita Roy‐Chowdhuri, Deepali Jain
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Virchows Archiv.2021; 478(1): 21. CrossRef
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Xiang Li, Hui Shi, Wei Zhang, Chong Bai, Miaoxia He, Na Ta, Haidong Huang, Yunye Ning, Chen Fang, Hao Qin, Yuchao Dong
Frontiers in Oncology.2021;[Epub] CrossRef
Prevalence of NUT carcinoma in head and neck: Analysis of 362 cases with literature review
Taebum Lee, Junhun Cho, Chung‐Hwan Baek, Young‐Ik Son, Han‐Sin Jeong, Man Ki Chung, Sang Duk Hong, Yong Chan Ahn, Dong Ryul Oh, Jae Myoung Noh, Keunchil Park, Myung‐Ju Ahn, Hyung‐Jin Kim, Yi Kyung Kim, Young Hyeh Ko
Head & Neck.2020; 42(5): 924. CrossRef
Lung nuclear protein in testis carcinoma in an elderly Korean woman: A case report with cytohistological analysis
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Thoracic Cancer.2020; 11(6): 1724. CrossRef
Clinicopathological characteristics of primary lung nuclear protein in testis carcinoma: A single‐institute experience of 10 cases
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Original Article

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.

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Neurosurgical Review.2022; 45(6): 3729. CrossRef
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Farhad Mashayekhi, Soheila Talesh Sasani, Alia Saberi, Zivar Salehi
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American Journal of Surgical Pathology.2021; 45(3): 329. CrossRef
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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
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Xiaodong Chen, Fen Tian, Peng Lun, Yugong Feng, Ho Lin
Evidence-Based Complementary and Alternative Medicine.2021; 2021: 1. CrossRef
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Journal of Neurosurgery.2019; 130(3): 1030. CrossRef
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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
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World Neurosurgery.2016; 93: 346. CrossRef

Case Study

Anaplastic Transformation of Papillary Thyroid Carcinoma in a Young Man: A Case Study with Immunohistochemical and BRAF Analysis: Ji Hye Park, Hyeong Ju Kwon, Cheong Soo Park, SoonWon Hong; Korean J Pathol. 2014;48(3):234-240. Published online June 26, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.3.234

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Abstract PDF

This study reports a case of anaplastic transformation from a well-differentiated thyroid carcinoma in a young patient. The first recurrent tissue contained poorly differentiated foci that revealed lower thyroglobulin, thyroid transcription factor 1 (TTF-1), and galectin-3 expression than the well-differentiated area. However there was no increased p53 or Ki-67 expression in the poorly differentiated foci, nor in the well-differentiated area. The tissue subsequently relapsed and revealed only anaplastic features, complete loss of thyroglobulin, TTF-1, and galectin-3 expression and revealed an increase in p53 and Ki-67 expression. The BRAF V600E and BRAF V600V mutation were found in the initially diagnosed papillary thyroid carcinoma and the poorly differentiated foci of the recurring papillary thyroid carcinoma; however, only the BRAF V600V mutation was found in the anaplastic carcinoma. These results suggest that overexpression of p53 and Ki-67 contributed to the anaplastic transformation. We also found that the BRAF type changed during the tumor relapse.

Citations

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Regressed Papillary Thyroid Carcinoma with Anaplastic Transformation into Lymph Node Metastasis: Case Report with Review of the Literature
Bozidar Kovacevic, Bojana Rancic, Sasa Jovic, Snezana Cerovic, Vesna Skuletic, Jelena Karajovic, Milka Gardasevic, Gordana Supic, Kennichi Kakudo
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Rare but Complex: Outcomes and Challenges in Managing Composite Follicular-Anaplastic Thyroid Cancer
Dilay Aykan, Hala al Asadi, Anjani Turaga, Lutske Lodewijk, Brendan M. Finnerty, Thomas J. Fahey, Inne H. M. Borel Rinkes, Menno R. Vriens, Rasa Zarnegar
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Coexisting well-differentiated and anaplastic thyroid carcinoma in the same primary resection specimen: immunophenotypic and genetic comparison of the two components in a consecutive series of 13 cases and a review of the literature
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HDAC Inhibition Induces PD-L1 Expression in a Novel Anaplastic Thyroid Cancer Cell Line
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Pathology & Oncology Research.2020; 26(4): 2523. CrossRef
EWSR1 rearrangement is a frequent event in papillary thyroid carcinoma and in carcinoma of the thyroid with Ewing family tumor elements (CEFTE)
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Original Articles

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

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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 the c-Met gene by fluorescence in 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.

Citations

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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
Pathogens.2021; 10(11): 1429. CrossRef
The roles of PTEN, cMET, and p16 in resistance to cetuximab in head and neck squamous cell carcinoma
Alexandre A. B. A. da Costa, Felipe D’Almeida Costa, Daniel Vilarim Araújo, Marcos Pedro Guedes Camandaroba, Victor Hugo Fonseca de Jesus, Audrey Oliveira, Ana Caroline Fonseca Alves, Carlos Stecca, Larissa Machado, Andrea Cruz Feraz de Oliveira, Thiago B
Medical Oncology.2019;[Epub] CrossRef
Role of c‐Met expression on prognosis of head and neck cancer: A literature review and meta‐analysis
Lei Li, Zhijun Sun, Xin Huang, Xiao Li, Lihua Sun, Lei Zhang, Xiaodan Zhang, Longwei Ye, Jie Yuan, Limin Mao, Guolin Li
Head & Neck.2019; 41(6): 1999. CrossRef
MET Genomic Alterations in Head and Neck Squamous Cell Carcinoma (HNSCC): Rapid Response to Crizotinib in a Patient with HNSCC with a Novel MET R1004G Mutation
Lisa Pei Chu, Debra Franck, Christine A. Parachoniak, Jeffrey P. Gregg, Michael G. Moore, D. Gregory Farwell, Shyam Rao, Andreas M. Heilmann, Rachel L. Erlich, Jeffrey S. Ross, Vincent A. Miller, Siraj Ali, Jonathan W. Riess
The Oncologist.2019; 24(10): 1305. CrossRef
Understanding c-MET signalling in squamous cell carcinoma of the head & neck
P. Szturz, E. Raymond, C. Abitbol, S. Albert, A. de Gramont, S. Faivre
Critical Reviews in Oncology/Hematology.2017; 111: 39. CrossRef
Prognostic value of c-MET in head and neck cancer: A systematic review and meta-analysis of aggregate data
Petr Szturz, Marie Budíková, Jan B. Vermorken, Ivana Horová, Břetislav Gál, Eric Raymond, Armand de Gramont, Sandrine Faivre
Oral Oncology.2017; 74: 68. CrossRef
Activated HGF-c-Met Axis in Head and Neck Cancer
Levi Arnold, Jonathan Enders, Sufi Thomas
Cancers.2017; 9(12): 169. CrossRef
Clinicopathological impacts of high c-Met expression in head and neck squamous cell carcinoma: a meta-analysis and review
Jung Han Kim, Bum Jun Kim, Hyeong Su Kim
Oncotarget.2017; 8(68): 113120. CrossRef
High expression of c‑Met and EGFR is associated with poor survival of patients with glottic laryngeal squamous cell carcinoma
Mei Jiang, Hui Zhang, He Xiao, Zhimin Zhang, Dan Que, Jia Luo, Jian Li, Bijing Mao, Yuanyuan Chen, Meilin Lan, Ge Wang, Hualiang Xiao
Oncology Letters.2017;[Epub] CrossRef
Profiling of cMET and HER Family Receptor Expression in Pancreatic Ductal Adenocarcinomas and Corresponding Lymph Node Metastasis to Assess Relevant Pathways for Targeted Therapies
Alexander Muckenhuber, Galina Babitzki, Marlene Thomas, Gabriele Hölzlwimmer, Magdalena Zajac, Moritz Jesinghaus, Frank Bergmann, Jens Werner, Albrecht Stenzinger, Wilko Weichert
Pancreas.2016; 45(8): 1167. CrossRef
Absent and abundant MET immunoreactivity is associated with poor prognosis of patients with oral and oropharyngeal squamous cell carcinoma
Maria J. De Herdt, Stefan M. Willems, Berdine van der Steen, Rob Noorlag, Esther I. Verhoef, Geert J.L.H. van Leenders, Robert J.J. van Es, Senada Koljenović, Robert J. Baatenburg de Jong, Leendert H.J. Looijenga
Oncotarget.2016; 7(11): 13167. CrossRef
Biological, diagnostic and therapeutic relevance of the MET receptor signaling in head and neck cancer
Lluís Nisa, Daniel Matthias Aebersold, Roland Giger, Yitzhak Zimmer, Michaela Medová
Pharmacology & Therapeutics.2014; 143(3): 337. CrossRef
Frequent hepatocyte growth factor overexpression and low frequency of c-Met gene amplification in human papillomavirus–negative tonsillar squamous cell carcinoma and their prognostic significances
Mi Jung Kwon, Dong Hoon Kim, Hye-Rim Park, Hyung Sik Shin, Ji Hyun Kwon, Dong Jin Lee, Jin Hwan Kim, Seong Jin Cho, Eun Sook Nam
Human Pathology.2014; 45(7): 1327. CrossRef
Distinct c-Met activation mechanisms induce cell rounding or invasion through pathways involving integrins, RhoA and HIP1
Anja Mai, Ghaffar Muharram, Rachel Barrow-McGee, Habib Baghirov, Juha Rantala, Stéphanie Kermorgant, Johanna Ivaska
Journal of Cell Science.2014; 127(9): 1938. CrossRef

Oncocytoma and Oncocytic Carcinoma of the Salivary Glands, Single Institute Experience.: Jeong Hyeon Jo, Seung Ho Choi, Jong Lyel Roh, Soon Yuhl Nam, Sang Yoon Kim, Kyung Ja Cho; Korean J Pathol. 2010;44(4):370-375.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.4.370

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Abstract PDF

BACKGROUND
Oncocytic neoplasms of the salivary glands are rare and the differential diagnosis between oncocytic carcinomas (OCs) and oncocytomas is difficult. We present 5 cases of oncocytoma and 3 cases of OC of the salivary glands with clinicopathological and immunohistochemical comparisons.
METHODS
Eight cases of oncocytic neoplasms diagnosed at Asan Medical Center between 1998 and 2009 were reviewed for clinical data and histological features. Immunohistochemical staining for epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (Her-2), c-kit, p53, and Ki-67 was done.
RESULTS
Cytological differences between oncocytomas and OCs were not obvious, but unequivocal infiltrative growths were identified in 3 cases, rendering the diagnosis of oncocytic carcinoma. When the remaining cases were classified as oncocytomas, there was no difference in age, size, and clinical symptoms between oncocytomas and OCs. Two of 3 OCs showed strong membranous expression of c-kit, but all oncocytomas were negative. The proportion of p53-positive cells was larger in OCs than oncocytomas. Her-2 or EGFR expression was absent, and Ki-67 labeling indices were less than 1% in all cases.
CONCLUSIONS
An infiltrative growth pattern, strong membranous expression of c-kit, and an increased proportion of p53-positive cells are features that can differentiate OCs from oncocytomas of the salivary glands.

Citations

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Primary oncocytic carcinoma of ectopic salivary gland: a unique case
E. Touli, A. Manganaris, C. Nikolaidou, I. Karasmanis
International Journal of Oral and Maxillofacial Surgery.2022; 51(4): 463. CrossRef

Immunohistochemical Array for Clear Cell Type Mucoepidermoid Carcinoma.: Yeon Sook Kim, Sang Shin Lee, Ji Yong Song, Eun Cheol Kim, Suk Keun Lee; Korean J Pathol. 2010;44(3):284-294.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.284

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Abstract PDF

BACKGROUND
The protein expression profile of clear cell type mucoepidermoid carcinoma (MEC) is not well known.
METHODS
We examined a case of clear cell type MEC by immunohistochemical (IHC) array using 59 antibodies against oncoproteins, proliferation-related proteins, apoptosis-related proteins, growth factor-related proteins, angiogenesis-related proteins, and matrix proteins.
RESULTS
MEC tumor cells showed 40 to 60% more expression of BCL-2 and cyclin-dependent kinase 4 than normal gingival tissue, and 20-40% more expression of BCL-2-associated agonist of cell death, deleted in malignant brain tumors 1, E-cadherin, eIF5A, hypoxia-inducible factor, vimentin, and Wnt-1. Expression of other proteins, including p53, epidermal growth factor receptor, proliferating cell nuclear antigen, survivin, carcinoembryonic antigen, beta-catenin, poly-ADP ribose-polymerase, etc. were relatively weak in MEC tumor cells.
CONCLUSIONS
The IHC array for our MEC contained strong oncogenic signals involving Wnt-1/adenomatous polyposis coli, tumor necrosis factor a/signal transducer and activator of transcription 3/BCL-2, and pAKT pathways, signals that could result in the prolonged survival of clear tumor cells.

Citations

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Adolescent tongue base tumour with diagnostic histopathological dilemma
Mousam Maiti, Ajay Mallick, Debangshu Ghosh, Indranil Chakrabarti
BMJ Case Reports.2024; 17(8): e259570. CrossRef
A review: Immunological markers for malignant salivary gland tumors
P.C. Anila Namboodiripad
Journal of Oral Biology and Craniofacial Research.2014; 4(2): 127. CrossRef
DISPLACEMENT OF MAXILLARY LATERAL INCISOR CAUSED BY IDIOPATHIC GINGIVAL FIBROMATOSIS
Ji-Sook Jung, Ho-Won Park, Ju-Hyun Lee, Hyun-Woo Seo, Suk-Keun Lee
THE JOURNAL OF THE KOREAN ACADEMY OF PEDTATRIC DENTISTRY.2011; 38(3): 296. CrossRef

Prognostic Value of Phosphorylated Akt and Survivin Expression in Gastric Adenocarcinoma.: Soong Lee, Yun Cheol Kim, Hyeon Min Lee, Ki Sang Lee, Byung Chul Shin, Hyung Seok Kim, Jae Hyuk Lee, Chang Soo Park, Kyung Hwa Lee; Korean J Pathol. 2010;44(3):252-258.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.252

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Abstract PDF

BACKGROUND
pAkt (the phosphorylated form of the proto-oncogene protein c-akt) and survivin (human BIRC5 protein) are candidate apoptosis-related molecules that may be responsible for cancer progression. The aim of this study was to determine the expression of pAkt and survivin in malignant stomach neoplasm, and their value as prognostic indicators of cancer.
METHODS
The expression of pAkt and survivin in 144 cases of gastric cancer was detected by immunohistochemistry and compared with established clinicopathological parameters and prognosis of this disease.
RESULTS
Expression of pAkt showed significant correlations with depth of invasion, lymph node and distant metastasis, as well as the stage (p < 0.05 for all three correlations), but not with the Lauren classification. Survivin expression closely correlated with histological type, Lauren classification, depth of invasion, metastasis, and stage (p < 0.05 for all). The overall survival of patients with pAkt/survivin expression was inferior to that of patients with loss of pAkt/survivin expression. Cox multivariate analysis demonstrated a significant correlation between stage (p = 0.04), survivin expression (p = 0.02), and prognosis.
CONCLUSIONS
Patients with pAkt/survivin expression in gastric cancer are at increased risk of cancer-related mortality via the apoptosis resistance pathway. Expression of pAkt and survivin could be used as a prognostic indicator for gastric cancer.

Citations

Citations to this article as recorded by

Transcriptome analysis reveals GPNMB as a potential therapeutic target for gastric cancer
Feifei Ren, Qitai Zhao, Bin Liu, Xiangdong Sun, Youcai Tang, Huang Huang, Lu Mei, Yong Yu, Hui Mo, Haibin Dong, Pengyuan Zheng, Yang Mi
Journal of Cellular Physiology.2020; 235(3): 2738. CrossRef
The Relationship Between Estrogen/Progesterone Receptor and Expression of mTOR/pAkt Proteins and the Analysis of Prognosis in Breast Cancer
Sun Wook Han, Moon Soo Lee, Sung Yong Kim, Gil Ho Kang, Zi Sun Kim, Cheol Wan Lim, Ji Hyun Lee, Hyun Ju Lee, Mee-Hye Oh, Min Hyuk Lee
Journal of Breast Disease.2013; 1(1): 8. CrossRef
Clinicopathological correlations of mTOR and pAkt expression in non-small cell lung cancer
Mee-Hye Oh, Hyun Ju Lee, Seol Bong Yoo, Xianhua Xu, Jae Sung Choi, Yong Hoon Kim, Seok Yeol Lee, Choon-Taek Lee, Sanghoon Jheon, Jin-Haeng Chung
Virchows Archiv.2012; 460(6): 601. CrossRef

KIT/PDGFRA Expression and Mutation in Testicular Seminoma and Ovarian Dysgerminoma.: Song Yi Choi, Kwang Sun Suh, Yong Beom Kim, Hyun Jeong Lee, Eun Sun Kim, Mee Ja Park; Korean J Pathol. 2009;43(6):528-534.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.6.528

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Abstract PDF

BACKGROUND
KIT and PDGFRA are tyrosine kinase receptors. Stem cell factor/KIT-mediated signaling plays a role in normal spermatogenesis, and the alteration of KIT is important in the pathogenesis of seminomas/dysgerminomas (SD). METHODS: To determine the role of expression and mutation of the KIT and PDGFRA genes, we analyzed 16 seminoma cases, 4 spermatocytic seminoma (SS) cases and 8 dysgerminoma cases for KIT and PDGFRA expression and mutation of KIT (exons 9, 11, 13, and 17) and PDGFRA (exons 12 and 18) using PCR-SSCP methods. RESULTS: KIT was immunohistochemically positive in all 24 SD cases, and one of four (25%) SS cases. PDGFRA was immunohistochemically evident in 16 of the 24 (66.6%) SD cases, and two of the four (50%) SS cases. KIT expression was significantly reduced in SS compared with seminoma (p=0.0035). Four cases (14.3%) displayed mutation in KIT exon 17 or PDGFRA exon 12. Distant metastasis was present in three cases (10.7%), one of which had a nonsense mutation in KIT. CONCLUSIONS: These results indicate that KIT is expressed in the majority of SD cases, but not in most SS cases. However, there was no significant correlation between the clinicopathologic features and mutation or expression of KIT and PDGFRA.

Citations

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Expression of DOG1, PDGFRA, and p16 in Gastrointestinal Stromal Tumors
Sung Hee Jung, Kwang Sun Suh, Dae Young Kang, Dong Wook Kang, Young-Beum Kim, Eun-Sun Kim
Gut and Liver.2011; 5(2): 171. CrossRef

Expression of P-glycoprotein and Apoptosis in Diffuse Large B-cell Lymphoma.: Ji Eun Kim, Young A Kim, Mee Soo Chang, Yunkyeong Jeon, JinHo Paik, Seon Og Yoon; Korean J Pathol. 2009;43(4):317-320.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.4.317

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Abstract PDF: BACKGROUND
Diffuse large B-cell lymphoma (DLBCL) is the most common type of malignant lymphoma which responds well to conventional chemotherapy. However, quite a few patients have a recurrence with more aggressive forms after completion of therapy. Multidrug resistance proteins (MRP) are related to this process in several ways such as cell cycle alteration and modulation of apoptosis. METHODS: We investigated the expression of P-glycoprotein (Gp), one of the well-known MRP, as well as apoptosis associated proteins in DLBCL. Immunohistochemical staining for Gp, p53, Bcl-2, Ki-67, active caspase 3 and FADD was done in forty DLBCL cases. The association between MRP and apoptosis associated proteins to clinical findings was also tested. RESULTS: Twenty-nine patients out of 40 (73%) with DLBCL were positive for Gp, and 26 cases (65%) had a strong positive for Gp. Gp expression was stronger in high-grade lesions than in low-grade lesions and was associated to Bcl-2 expression. However, we could not find an adverse impact of Gp expression on patients' overall survival or relapse free survival rate. CONCLUSIONS: Our study revealed a high frequency of expression for Gp in DLBCL with a possible relationship between the expressions of Gp to apoptosis associated proteins.

Primary Extragastrointestinal Stromal Tumor (EGIST) of the Greater Omentum.: Kyung Un Choi, Jee Yeun Kim, Do Youn Park, Chang Hun Lee, Mee Young Sol, Kang Suek Suh, Jun Woo Lee; Korean J Pathol. 2001;35(4):347-350.

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Abstract PDF: Gastrointestinal stromal tumors (GISTs) were recently defined as spindle cell, epithelioid, or occasionally, pleomorphic mesenchymal tumors of the gastrointestinal tract that express the CD117 (proto-oncogene c-kit protein, stem cell factor receptor), as detected using immunohistochemistry. And they show a new tendency to include the CD117-positive mesenchymal spindle cell or epithelioid neoplasms primary in the omentum and mesentery, and is so termed extragastrointestinal stromal tumors (EGISTs). Omental EGISTs are very rare and similar to their gastrointestinal counterpart. We present a case of primary EGIST of the greater omentum in a 58-year-old man. The resected tumor mass measured 20X15X5 cm and weighed 1,150 g. The cut surface displayed a central cystic change and partial mural nodules. Microscopically, most parts of the tumor were composed of round or polygonal cells, with many of them containing perinuclear vacuoles. The mitotic count was less than one per 50 high-power-fields. Immunohistochemically, the tumor cells were diffusely positive for CD117 and vimentin, and focally for smooth muscle actin and CD34. Ultrastructurally, partially smooth muscle differentiation was confirmed in this case.

Immunohistochemical Expression of CD117, CD34, Vimentin and alpha-Smooth Muscle Actin in Gastrointestinal Stromal Tumors.: Jong Kuk Kim, O Jun Kwon, Byung Heon Kim; Korean J Pathol. 2001;35(6):506-512.

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Abstract: BACKGROUND
The interstitial cell of Cajal (ICC), the cell of origin for gastrointestinal stromal tumor (GIST), expresses CD117 (c-kit) which is a receptor for KIT ligand in cell membranes. It is immunohistochemically positive for CD117, CD34 and vimentin, but not for alpha-smooth muscle actin (SMA).
METHODS
We performed the immunohistochmical study with anti-CD117, anti-CD34, anti-VMT and anti-alpha-SMA in paraffin-embedded tissue of 28 GISTs and 19 smooth muscle tumors arising in the gastrointestinal tract, mesentery, omentum and retroperitoneum (GISMT) to determine the precise nature of GIST cells.
RESULTS
The positive rates of CD117, CD34 and vimentin in extraGISTs were significantly higher than in GISMTs. The positive rate of alpha-SMA in GIST was not significantly different than in GISMTs.
CONCLUSIONS
A subset of GISTs may express alpha-SMA as well as CD117 and the cell of their origin may be a ICC precursor cell which is capable of differentiating bidirectionally into ICC and smooth muscle cell. This explains why GISTs may arise out of gut where ICC is not present and that they may represent the tumors arising from ICC precursor cell present around the gastrointestinal tract.

Clinicopathological Analysis of Systemic Anaplastic Large Cell Lymphoma.: Soo Young Chung, Han Suk Ryu, Jae Soo Ko, Baek Youl Ryoo, Seung Sook Lee; Korean J Pathol. 2006;40(6):399-405.

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Abstract PDF: BACKGROUND
Several studies from western countries have reported variable prognoses for patients with systemic anaplastic large cell lymphoma (ALCL) depending strongly on the expression of anaplastic lymphoma kinase (ALK). However, no prognostic significance of ALK expression in Koreans was reported in a single report regarding these patients, although the number of cases was limited in that study.
METHODS
We analyzed the clinicopathological features of ALK+ ALCL and ALK- ALCL in 30 Korean patients diagnosed with primary systemic ALCL.
RESULTS
ALK expression was detected in 60% of all ALCL patients (18/30), and there was no statistical significance to ALK expression in overall survival. Patients with ALK+ ALCL were younger in age and had negative bcl-2 expression; these differences were statistically significant. Tumors positive for ALK protein and granzyme B expression, and negative for bcl-2 expression with a null-cell phenotype tended to have better survival outcomes, althought this trend failed to reach statistical significance (p<0.2), probably due to the limited number of cases in this study.
CONCLUSION
ALK protein expression and the absence of bcl-2 in tumor cells tend to result in better survival despite the failure of this trend to achieve statistical significance. Further studies that examine potential pathologic prognostic factors combined with the expression of ALK and apoptotic factors such as bcl-2 are needed. Additional larger-scale studies are also needed to conclude that ALK expression has no prognostic significance among Koreans.

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