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Original Article
Special AT-rich sequence-binding protein 2 (SATB2) in the differential diagnosis of osteogenic and non-osteogenic bone and soft tissue tumors
Sharon Milton, Anne Jennifer Prabhu, V. T. K. Titus, Rikki John, Selvamani Backianathan, Vrisha Madhuri
J Pathol Transl Med. 2022;56(5):270-280.   Published online September 13, 2022
DOI: https://doi.org/10.4132/jptm.2022.07.11
  • 1,951 View
  • 76 Download
  • 1 Web of Science
  • 1 Crossref
AbstractAbstract PDF
Background
The diagnosis of osteosarcoma (OSA) depends on clinicopathological and radiological correlation. A biopsy is considered the gold standard for OSA diagnosis. However, since OSA is a great histological mimicker, diagnostic challenges exist. Immunohistochemistry (IHC) can serve as an adjunct for the histological diagnosis of OSA. Special AT-rich sequence-binding protein 2 (SATB2) was recently described as a reliable adjunct immunohistochemical marker for the diagnosis of OSA.
Methods
We investigated the IHC expression of SATB2 in 95 OSA and 100 non-osteogenic bone and soft tissue tumors using a monoclonal antibody (clone EPNCIR30A). The diagnostic utility of SATB2 and correlation with clinicopathological parameters were analyzed.
Results
SATB2 IHC was positive in 88 out of 95 cases (92.6%) of OSA and 50 out of 100 cases (50.0%) of primary non-osteogenic bone and soft tissue tumors. Of the 59 bone tumors, 37 cases (62.7%) were positive for SATB2, and of the 41 soft tissue tumors, 13 cases (31.7%) were positive for SATB2. The sensitivity of SATB2 as a diagnostic test was 92.6%, specificity 50%, positive predictive value 63.8%, and negative predictive value 87.7%.
Conclusions
Although SATB2 is a useful diagnostic marker for OSA, other clinical, histological and immunohistochemical features should be considered for the interpretation of SATB2.

Citations

Citations to this article as recorded by  
  • Favorable treatment response to high‐grade sarcoma in neurofibromatosis 1
    Michelle H. Talukder, Mauli M. Patel, Tala Al‐Saghir, Ghadir K. Katato, Janet Poulik, William J. Powell, Alysia K. Kemp, Steven Miller, Danielle Bell, Jeffrey W. Taub
    Pediatric Blood & Cancer.2023;[Epub]     CrossRef
Case Study
Colorectal adenocarcinoma with enteroblastic differentiation: diagnostic challenges of a rare case encountered in clinical practice
Evi Abada, Ifeoma C. Anaya, Othuke Abada, Anthony Lebbos, Rafic Beydoun
J Pathol Transl Med. 2022;56(2):97-102.   Published online January 21, 2022
DOI: https://doi.org/10.4132/jptm.2021.10.28
  • 3,877 View
  • 159 Download
  • 4 Web of Science
  • 4 Crossref
AbstractAbstract PDF
Colorectal adenocarcinoma with enteroblastic differentiation (CAED) is a rare subtype of colonic adenocarcinoma characterized by increased α-fetoprotein (AFP) production and the expression of at least one enteroblastic marker including AFP, glypican 3 (GPC3), or Spalt like transcription factor 4 (SALL4). We report a case of a 26-year-old female who presented with low back pain and constipation which persisted despite supportive measures. Imaging revealed multiple liver lesions and enlarged retroperitoneal nodes. Tumor markers including AFP were markedly elevated. On biopsy, samples from the liver revealed infiltrating glands lined by columnar-type epithelium with mostly eosinophilic granular to focally clear cytoplasm. By immunohistochemistry, the tumor showed immunoreactivity with AFP, hepatocyte antigen, GPC3, SALL4, CDX2, SATB2, and cytokeratin 20. A colonoscopy performed subsequently revealed a mass in the sigmoid colon and biopsy of this mass revealed a similar histology as that seen in the liver. A diagnosis of CAED was made, following the results of gene expression profiling by the tumor with next-generation sequencing which identified pathogenic variants in MUTYH, TP53, and KDM6A genes and therefore supported its colonic origin. Cases such as this underscores the use of ancillary diagnostic techniques in arriving at the correct diagnosis in lesions with overlapping clinicopathologic characteristics.

Citations

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  • Ureteral Metastasis of Colonic Adenocarcinoma with Enteroblastic Differentiation: A Rare Case to be Distinguished from Clear Cell Adenocarcinoma of the Urinary Tract
    Hiroshi Minato, Akane Yoshikawa, Sho Tsuyama, Kazuyoshi Katayanagi, Kengo Hayashi, Yusuke Sakimura, Hiroyuki Bando, Tomohiro Hori, Yosuke Kito
    International Journal of Surgical Pathology.2023; 31(8): 1553.     CrossRef
  • Beyond liver cancer, more application scenarios for alpha-fetoprotein in clinical practice
    Chenyu Ma, Yuexinzi Jin, Yuhan Wang, Huaguo Xu, Jiexin Zhang
    Frontiers in Oncology.2023;[Epub]     CrossRef
  • AIEgens assisted label free DNA supersandwich immunoassay for ultrasensitive α-fetoprotein detection
    Xiaowen Ou, Jingman Dai, Yiting Huang, Xiaoqin Xiong, Zhi Zheng, Xiaoding Lou, Fan Xia
    Giant.2022; 11: 100110.     CrossRef
  • Rectal carcinoma with dual differentiation toward enteroblastic and neuroendocrine features arising in a patient with ulcerative colitis: a case report
    Takako Kihara, Ryuichi Kuwahara, Kurando Kusunoki, Tomohiro Minagawa, Yuki Horio, Motoi Uchino, Hiroki Ikeuchi, Seiichi Hirota
    World Journal of Surgical Oncology.2022;[Epub]     CrossRef
Original Article
SMARCA4/BRG1 protein-deficient thoracic tumors dictate re-examination of small biopsy reporting in non–small cell lung cancer
Anurag Mehta, Divya Bansal, Rupal Tripathi, Ankush Jajodia
J Pathol Transl Med. 2021;55(5):307-316.   Published online June 21, 2021
DOI: https://doi.org/10.4132/jptm.2021.05.11
  • 5,807 View
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  • 4 Web of Science
  • 5 Crossref
AbstractAbstract PDF
Background
SMARCA4/BRG1 protein–deficient lung adenocarcinomas and thoracic sarcoma are recently described entities that lack distinctive histological features, transcription termination factor 1 (TTF1) reactivity, and actionable driver mutations. The current diagnostic path for small lung biopsies as recommended by the World Health Organization (WHO, 2015) is likely to categorize these as non– small cell carcinoma–not otherwise specified (NSCC-NOS). The present study attempts to define the subtle but distinctive clinicopathologic features of SMARCA4/BRG1 protein-deficient thoracic tumors; highlight their unique biology; and addresses the unmet need to segregate these using a new, tissue-proficient diagnostic pathway.
Methods
All lung biopsies and those from metastatic sites in patients with suspected advanced lung cancer and classified as NSCC-NOS as per WHO (2015) guidelines were subjected to BRG1 testing by immunohistochemistry. SMARCA4/BRG1 protein–deficient thoracic tumors were evaluated by an extended immunohistochemistry panel. Predictive biomarker and programmed death–ligand 1 testing was conducted in all cases.
Results
Of 110 cases, nine were found to be SMARCA4/BRG1 protein-deficient; six were identified as SMARCA4/BRG1 protein–deficient lung adenocarcinomas, and three were SMARCA4/BRG1 protein-deficient thoracic sarcomas. The histology ranged from poorly differentiated to undifferentiated to rhabdoid. None of the cases showed significant expression of TTF1 or p40, and no actionable mutation was identified.
Conclusions
It is difficult to separate BRG1-deficient lung adenocarcinomas and thoracic sarcomas based on morphology alone. We propose a diagnostic pathway for small biopsies of thoracic tumors to segregate these distinct entities so that they can be studied more efficaciously for new biomarkers and therapeutic options.

Citations

Citations to this article as recorded by  
  • Case report: The first account of undifferentiated sarcoma with epithelioid features originating in the pleura
    Ling-Xi Xiao, Li Liu, Wang Deng
    Frontiers in Medicine.2024;[Epub]     CrossRef
  • Chemotherapy and Immune Checkpoint Inhibitors in a Case of SMARCA4-dUT: A Case Report and Review of Literature
    Akriti Pokhrel, Ruchi Yadav, Kapil Kumar Manvar, Richard Wu, Vijay Jaswani, Carrie Brooke Wasserman, Jen C. Wang
    Journal of Investigative Medicine High Impact Case Reports.2023; 11: 232470962311762.     CrossRef
  • TTF1-positive SMARCA4/BRG1 deficient lung adenocarcinoma
    Anurag Mehta, Himanshi Diwan, Divya Bansal, Manoj Gupta
    Journal of Pathology and Translational Medicine.2022; 56(1): 53.     CrossRef
  • Delineation of a SMARCA4-specific competing endogenous RNA network and its function in hepatocellular carcinoma
    Lei Zhang, Ting Sun, Xiao-Ye Wu, Fa-Ming Fei, Zhen-Zhen Gao
    World Journal of Clinical Cases.2022; 10(29): 10501.     CrossRef
  • Artificial intelligence platform, RADR®, aids in the discovery of DNA damaging agent for the ultra-rare cancer Atypical Teratoid Rhabdoid Tumors
    Joseph McDermott, Drew Sturtevant, Umesh Kathad, Sudhir Varma, Jianli Zhou, Aditya Kulkarni, Neha Biyani, Caleb Schimke, William C. Reinhold, Fathi Elloumi, Peter Carr, Yves Pommier, Kishor Bhatia
    Frontiers in Drug Discovery.2022;[Epub]     CrossRef
Case Study
Hepatoid thymic carcinoma: a case report of a rare subtype of thymic carcinoma
Ji-Seon Jeong, Hyo Jeong Kang, Uiree Jo, Min Jeong Song, Soon Yeol Nam, Joon Seon Song
J Pathol Transl Med. 2021;55(3):230-234.   Published online April 14, 2021
DOI: https://doi.org/10.4132/jptm.2021.03.10
  • 2,786 View
  • 103 Download
  • 3 Web of Science
  • 1 Crossref
AbstractAbstract PDF
Hepatoid thymic carcinoma is an extremely rare subtype of primary thymus tumor resembling “pure” hepatoid adenocarcinomas with hepatocyte paraffin 1 (Hep-Par-1) expression. A 53-year-old man presented with voice change and a neck mass. Multiple masses involving the thyroid, cervical and mediastinal lymph nodes, and lung were detected on computed tomography. Papillary thyroid carcinoma was confirmed by biopsy, and the patient underwent neoadjuvant chemoradiation therapy. However, the anterior mediastinal mass was enlarged after the treatment whereas the multiple masses in the thyroid and neck decreased in size. Microscopically, polygonal tumor cells formed solid sheets or trabeculae resembling hepatocytes and infiltrated remnant thymus. The tumor cells showed immunopositivity for cytokeratin 7, cytokeratin 19, and Hep-Par-1 and negativity for α-fetoprotein. Possibilities of germ cell tumor, squamous cell carcinoma, and metastasis of thyroid papillary carcinoma were excluded by immunohistochemistry. This report on the new subtype of thymic carcinoma is the third in English literature thus far.

Citations

Citations to this article as recorded by  
  • Hepatoid tumors of the gastrointestinal/pancreatobiliary district: morphology, immunohistochemistry, and molecular profiles
    Paola Mattiolo, Aldo Scarpa, Claudio Luchini
    Human Pathology.2023; 132: 169.     CrossRef
Original Articles
Gene variant profiles and tumor metabolic activity as measured by FOXM1 expression and glucose uptake in lung adenocarcinoma
Ashley Goodman, Waqas Mahmud, Lela Buckingham
J Pathol Transl Med. 2020;54(3):237-245.   Published online March 4, 2020
DOI: https://doi.org/10.4132/jptm.2020.02.08
  • 4,714 View
  • 112 Download
  • 1 Web of Science
AbstractAbstract PDF
Background
Cancer cells displaying aberrant metabolism switch energy production from oxidative phosphorylation to glycolysis. Measure of glucose standardized uptake value (SUV) by positron emission tomography (PET), used for staging of adenocarcinoma in high-risk patients, can reflect cellular use of the glycolysis pathway. The transcription factor, FOXM1 plays a role in regulation of glycolytic genes. Cancer cell transformation is driven by mutations in tumor suppressor genes such as TP53 and STK11 and oncogenes such as KRAS and EGFR. In this study, SUV and FOXM1 gene expression were compared in the background of selected cancer gene mutations.
Methods
Archival tumor tissue from cases of lung adenocarcinoma were analyzed. SUV was collected from patient records. FOXM1 gene expression was assessed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Gene mutations were detected by allele-specific PCR and gene sequencing.
Results
SUV and FOXM1 gene expression patterns differed in the presence of single and coexisting gene mutations. Gene mutations affected SUV and FOXM1 differently. EGFR mutations were found in tumors with lower FOXM1 expression but did not affect SUV. Tumors with TP53 mutations had increased SUV (p = .029). FOXM1 expression was significantly higher in tumors with STK11 mutations alone (p < .001) and in combination with KRAS or TP53 mutations (p < .001 and p = .002, respectively).
Conclusions
Cancer gene mutations may affect tumor metabolic activity. These observations support consideration of tumor cell metabolic state in the presence of gene mutations for optimal prognosis and treatment strategy.
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
  • 7,759 View
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  • 22 Web of Science
  • 25 Crossref
AbstractAbstract 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.

Citations

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  • Immunohistochemical Characterization of a Large Cohort of Triple Negative Breast Cancer
    Rachel Han, Sharon Nofech-Mozes, Dina Boles, Hannah Wu, Nikolina Curcin, Elzbieta Slodkowska
    International Journal of Surgical Pathology.2024; 32(2): 239.     CrossRef
  • The Challenge of “Monomorphic” Mucoepidermoid Carcinoma—Report of a Rare Case with Pure Spindle-Clear Cell Morphology
    Xinyi Qu, Edwin Jun Chen Chew, Sathiyamoorthy Selvarajan, Bingcheng Wu, Abbas Agaimy, Fredrik Petersson
    Head and Neck Pathology.2023; 17(3): 864.     CrossRef
  • SOX10
    Albert L Sy, Mai P Hoang
    Journal of Clinical Pathology.2023; 76(10): 649.     CrossRef
  • Activating Transcription Factor 1 (ATF1) Immunohistochemical Marker Distinguishes HCCC from MEC
    Wafaey Badawy, Asmaa S. Abdelfattah, Haneen A. Sallam
    Journal of Molecular Pathology.2023; 4(3): 178.     CrossRef
  • Rare case of pleomorphic adenoma presenting as peritonsilar tumor
    Anđelina Jovanović, Svetlana Valjarević, Milan Jovanović
    Medicinska istrazivanja.2023; 56(3): 95.     CrossRef
  • Pleomorphic Adenoma of a Minor Salivary Gland of the Hard Palate: A Case Report
    Ishank Panchal, Anil Wanjari
    Cureus.2023;[Epub]     CrossRef
  • Advanced Diagnostic Methods for Salivary Glands Diseases: A Narrative Review Study
    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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  • Clinical Significance of SOX10 Expression in Human Pathology
    Hisham F. Bahmad, Aran Thiravialingam, Karthik Sriganeshan, Jeffrey Gonzalez, Veronica Alvarez, Stephanie Ocejo, Alvaro R. Abreu, Rima Avellan, Alejandro H. Arzola, Sana Hachem, Robert Poppiti
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    Cancers.2022; 14(3): 476.     CrossRef
  • Diagnostic accuracy of human transcriptional activator (Myb) expression by ELISA technique versus immunohistochemistry in detecting salivary gland carcinomas
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    Journal of International Oral Health.2022; 14(1): 61.     CrossRef
  • SLUG is a key regulator of epithelial-mesenchymal transition in pleomorphic adenoma
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    Laboratory Investigation.2022; 102(6): 631.     CrossRef
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    Human Pathology.2022; 127: 86.     CrossRef
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  • Co-expression of Myoepithelial and Melanocytic Features in Carcinoma Ex Pleomorphic Adenoma
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    Head and Neck Pathology.2021; 15(4): 1385.     CrossRef
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Significance of Intratumoral Fibrosis in Clear Cell Renal Cell Carcinoma
Jae Won Joung, Hoon Kyu Oh, Sun Jae Lee, Young Ah Kim, Hyun Jin Jung
J Pathol Transl Med. 2018;52(5):323-330.   Published online August 19, 2018
DOI: https://doi.org/10.4132/jptm.2018.07.21
  • 6,032 View
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  • 16 Web of Science
  • 15 Crossref
AbstractAbstract PDF
Background
Intratumoral fibrosis (ITF) is a frequent histologic finding in solid organ tumors. Renal cell carcinoma (RCC) is a highly vascularized tumor with different shapes and degrees of ITF and inflammation. ITF is a poor prognostic factor, especially in breast cancer, and is related to intratumoral necrosis (ITN) and intratumoral inflammation (ITI). However, the significance of ITF in RCC has not been fully studied. In this study, we evaluate the relationships between ITF and other clinicopathologic parameters associated with RCC prognosis.
Methods
ITF was evaluated in 204 clear cell renal cell carcinoma (CCRCC) specimens according to presence and grade of fibrosis, degree of ITI, and presence of ITN. Lysyl oxidase (LOX) expression in tumor cells was also evaluated with clinicopathologic parameters.
Results
Among 204 CCRCC cases, 167 (81.7%) showed ITF, 71 (34.8%) showed ITI, 35 (17.2%) showed ITN, and 111 (54.4%) showed LOX expression. ITF correlated with Fuhrman nuclear grade (p = .046), lymphovascular invasion (LVI) (p = .027), and ITN (p = .036). Patients with ITF had a poor five-year overall survival rate (p = .104).
Conclusions
ITF is related to other poor prognostic factors in CCRCC, such as Fuhrman nuclear grade, ITN, and LVI, but ITF itself had no significant correlation with prognosis of CCRCC.

Citations

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Interleukin-31, Interleukin-31RA, and OSMR Expression Levels in Post-burn Hypertrophic Scars
Mi Young Lee, Eun Shin, Hyunchul Kim, In Suk Kwak, Younghee Choi
J Pathol Transl Med. 2018;52(5):307-313.   Published online August 16, 2018
DOI: https://doi.org/10.4132/jptm.2018.08.03
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  • 182 Download
  • 8 Web of Science
  • 8 Crossref
AbstractAbstract PDF
Background
Although several studies have shown the role of interleukin-31 (IL-31) and its receptors in inducing pruritus in certain skin disorders, knowledge of its role in post-burn hypertrophic scars is insufficient. Therefore, the histopathological expression levels of IL-31, IL-31 receptor alpha (IL-31RA), and oncostatin M receptor (OSMR) in post-burn hypertrophic scar tissues were investigated and compared with normal tissue expression levels.
Methods
Samples of hypertrophic scar tissue were obtained from 20 burn patients through punch biopsy. Normal samples were obtained from areas adjacent to the burn injury site of the same patients. Samples were placed in 10% neutral buffered formalin, embedded in paraplast, and processed into serial 5-μm sections. Immunohistochemistry results were semi-quantitatively evaluated for IL-31, IL-31RA, and OSMR. By hematoxylin and eosin staining, epidermal and dermal thickness were assessed with a microscope and digital camera. Intensities were rated on a scale of 1 to 4.
Results
Percentages for IL-31, IL-31RA, and OSMR in the epidermal basal layer cell cytoplasm were significantly greater in the burn scar tissue compared to normal skin, as well as the dermal and epidermal thickness (p < .05). There was a significant difference in IL-31 epidermal basal layer intensity in burn scar tissue compared to normal skin (p < .05). Besides the OSMR basal layer intensity, IL-31 and IL-31RA intensities between the burn scar and normal tissues were not significant. However, correlations were significant, indicating that the greater the infiltration percentage, the higher the intensity (p < .05).
Conclusions
IL-31, IL-31RA, and OSMR expression levels are increased in hypertrophic scars compared with normal tissue.

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    N. E. E. Van Loey, A. E. E. de Jong, H. W. C. Hofland, A. I. M. van Laarhoven
    Frontiers in Medicine.2022;[Epub]     CrossRef
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    Sonja Ständer, Gil Yosipovitch, Franz J. Legat, Jean-Philippe Lacour, Carle Paul, Joanna Narbutt, Thomas Bieber, Laurent Misery, Andreas Wollenberg, Adam Reich, Faiz Ahmad, Christophe Piketty
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  • Post-Burn Pruritus
    Bo Young Chung, Han Bi Kim, Min Je Jung, Seok Young Kang, In-Suk Kwak, Chun Wook Park, Hye One Kim
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    Cosmin I. Ciotu, Michael J.M. Fischer
    Neurotherapeutics.2020; 17(3): 784.     CrossRef
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    Emilie Fowler, Gil Yosipovitch
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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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AbstractAbstract 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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  • BRD3‐NUTM1‐expressing NUT carcinoma of lung on endobronchial ultrasound‐guided transbronchial needle aspiration cytology, a diagnostic pitfall
    Sameer Chhetri Aryal, Shereen Zia, Shannon Rodgers, Yulei Shen, Kyle Perry, Lisi Yuan
    Diagnostic Cytopathology.2022;[Epub]     CrossRef
  • Nuclear protein of the testis midline carcinoma of the thorax
    Ayae Saiki, Keita Sakamoto, Yuan Bee, Takehiro Izumo
    Japanese Journal of Clinical Oncology.2022; 52(6): 531.     CrossRef
  • Approach to Mediastinal Fine Needle Aspiration Cytology
    Zaibo Li, Huihong Xu, Fang Fan
    Advances in Anatomic Pathology.2022; 29(6): 337.     CrossRef
  • Diagnosis, Treatment and Prognosis of Primary Pulmonary NUT Carcinoma: A Literature Review
    Jiaqian Yuan, Zhili Xu, Yong Guo
    Current Oncology.2022; 29(10): 6807.     CrossRef
  • Case report: Immunovirotherapy as a novel add-on treatment in a patient with thoracic NUT carcinoma
    Linus D. Kloker, Branko Calukovic, Katrin Benzler, Alexander Golf, Sebastian Böhm, Sven Günther, Marius Horger, Simone Haas, Susanne Berchtold, Julia Beil, Mary E. Carter, Tina Ganzenmueller, Stephan Singer, Abbas Agaimy, Robert Stöhr, Arndt Hartmann, Tho
    Frontiers in Oncology.2022;[Epub]     CrossRef
  • Cytomorphology of primary pulmonary NUT carcinoma in different cytology preparations
    Rimlee Dutta, Aruna Nambirajan, Saurabh Mittal, Sinchita Roy‐Chowdhuri, Deepali Jain
    Cancer Cytopathology.2021; 129(1): 53.     CrossRef
  • Update on genetically defined lung neoplasms: NUT carcinoma and thoracic SMARCA4-deficient undifferentiated tumors
    Kyriakos Chatzopoulos, Jennifer M. Boland
    Virchows Archiv.2021; 478(1): 21.     CrossRef
  • Immunotherapy and Targeting the Tumor Microenvironment: Current Place and New Insights in Primary Pulmonary NUT Carcinoma
    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
    Hwa Jin Cho, Hyun‐Kyung Lee
    Thoracic Cancer.2020; 11(6): 1724.     CrossRef
  • Clinicopathological characteristics of primary lung nuclear protein in testis carcinoma: A single‐institute experience of 10 cases
    Yoon Ah Cho, Yoon‐La Choi, Inwoo Hwang, Kyungjong Lee, Jong Ho Cho, Joungho Han
    Thoracic Cancer.2020; 11(11): 3205.     CrossRef
Original Articles
C-reactive Protein Overexpression in the Background Liver of Hepatitis B Virus–Associated Hepatocellular Carcinoma Is a Prognostic Biomarker
Jin Ho Shin, Eunsil Yu, Eun Na Kim, Chong Jai Kim
J Pathol Transl Med. 2018;52(5):267-274.   Published online July 27, 2018
DOI: https://doi.org/10.4132/jptm.2018.07.14
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AbstractAbstract PDF
Background
Chronic hepatitis B virus (HBV) infection is a leading cause of hepatocellular carcinoma (HCC). Peripheral blood C-reactive protein (CRP) concentration and CRP overexpression in HCC cells are proven to be prognostic markers for HCC, but the significance of CRP expression in non-neoplastic hepatocytes, which are the primary origin of CRP, has not been studied. This study was conducted to determine the clinicopathologic significance of CRP immunoreactivity in the background liver of HBV-associated HCC.
Methods
CRP immunostaining was done on tissue microarrays of non-neoplastic liver tissues obtained from surgically resected, treatment-naïve HBV-associated HCCs (n = 156). The relationship between CRP immunoreactivity and other clinicopathologic parameters including cancer-specific survival was analyzed. CRP immunoreactivity was determined using a 4-tier grading system: grades 0, 1, 2, and 3.
Results
CRP was positive in 139 of 156 cases (89.1%) of non-neoplastic liver in patients with HCCs: grade 1 in 83 cases (53.2%); grade 2 in 50 cases (32.1%); and grade 3 in six cases (3.8%). The patients with diffuse CRP immunoreactivity (grade 3) had decreased cancer-specific survival (p = .031) and a tendency for shorter interval before early recurrence (p = .050). The degree of CRP immunoreactivity correlated with serum CRP concentration (p < .001).
Conclusions
CRP immunoreactivity in non-neoplastic liver is a novel biomarker for poor cancer-specific survival of HBV-associated HCC and correlates with serum CRP concentration.

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  • Ferritin and procalcitonin serve as discriminative inflammatory biomarkers and can predict the prognosis of severe fever with thrombocytopenia syndrome in its early stages
    Keping Chen, Huidi Sun, Yu Geng, Chuankun Yang, Chun Shan, Yuxin Chen
    Frontiers in Microbiology.2023;[Epub]     CrossRef
  • Evaluation of Serum Ferritin, Procalcitonin, and C-Reactive Protein for the Prediction of Severity and Mortality in Hemorrhagic Fever With Renal Syndrome
    Lihe Che, Zedong Wang, Na Du, Liang Li, Yinghua Zhao, Kaiyu Zhang, Quan Liu
    Frontiers in Microbiology.2022;[Epub]     CrossRef
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    Haeryoung Kim, Young Nyun Park
    Journal of Pathology and Translational Medicine.2021; 55(3): 171.     CrossRef
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    Sarah Tan Siyin, Tong Liu, Wenqiang Li, Nan Yao, Guoshuai Xu, Jun Qu, Yajun Chen
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    Sukhpal Singh, Abhishek Bansal, Pardeep Kumar
    International Journal of Infection.2020;[Epub]     CrossRef
Myoferlin Expression and Its Correlation with FIGO Histologic Grading in Early-Stage Endometrioid Carcinoma
Min Hye Kim, Dae Hyun Song, Gyung Hyuck Ko, Jeong Hee Lee, Dong Chul Kim, Jung Wook Yang, Hyang Im Lee, Hyo Jung An, Jong Sil Lee
J Pathol Transl Med. 2018;52(2):93-97.   Published online March 14, 2018
DOI: https://doi.org/10.4132/jptm.2017.11.29
  • 5,868 View
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AbstractAbstract PDF
Background
For endometrioid carcinoma patients, International Federation of Gynecologists and Obstetricians (FIGO) histologic grading is very important for identifying the appropriate treatment method. However, the interobserver discrepancy with this three-tiered grading system is a serious potential problem. In this study, we used immunohistochemistry to analyze the relationship between FIGO histologic grading score and myoferlin expression.
Methods
We studied the endometrioid carcinoma tissues of 60 patients from Gyeongsang National University Hospital between January 2002 and December 2009. Immunohistochemical analysis of myoferlin was performed on tissue microarray blocks from surgical specimens.
Results
Myoferlin expression was observed in 58 of 60 patients. Moderate and strong myoferlin expression was observed in low-grade endometrioid carcinoma, while there was a tendency toward loss of myoferlin expression in high-grade endometrioid carcinoma (p<.001).
Conclusions
Our study revealed that myoferlin loss is significantly correlated with high FIGO grade of endometrioid carcinoma.

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  • Neoexpression of JUNO in Oral Tumors Is Accompanied with the Complete Suppression of Four Other Genes and Suggests the Application of New Biomarker Tools
    Dominik Kraus, Simone Weider, Rainer Probstmeier, Jochen Winter
    Journal of Personalized Medicine.2022; 12(3): 494.     CrossRef
  • Correlation between myoferlin expression and lymph node metastasis in papillary thyroid carcinoma
    Ji Min Na, Dong Chul Kim, Dae Hyun Song, Hyo Jung An, Hyun Min Koh, Jeong-Hee Lee, Jong Sil Lee, Jung Wook Yang, Min Hye Kim
    Journal of Pathology and Translational Medicine.2022; 56(4): 199.     CrossRef
  • PINCH-1 interacts with myoferlin to promote breast cancer progression and metastasis
    Tao Qian, Chengmin Liu, Yanyan Ding, Chen Guo, Renwei Cai, Xiaoxia Wang, Rong Wang, Kuo Zhang, Li Zhou, Yi Deng, Chuanyue Wu, Ying Sun
    Oncogene.2020; 39(10): 2069.     CrossRef
  • Human colon cancer cells highly express myoferlin to maintain a fit mitochondrial network and escape p53-driven apoptosis
    Gilles Rademaker, Brunella Costanza, Justine Bellier, Michael Herfs, Raphaël Peiffer, Ferman Agirman, Naïma Maloujahmoum, Yvette Habraken, Philippe Delvenne, Akeila Bellahcène, Vincent Castronovo, Olivier Peulen
    Oncogenesis.2019;[Epub]     CrossRef
  • Prognostic significance of immunohistochemical staining for myoferlin in clear cell renal cell carcinoma and its association with epidermal growth factor receptor expression
    Minsun Jung, Cheol Lee, Jeong Hwan Park, Kyung Chul Moon
    Urologic Oncology: Seminars and Original Investigations.2019; 37(11): 812.e9.     CrossRef
  • Ferlin Overview: From Membrane to Cancer Biology
    Peulen, Rademaker, Anania, Turtoi, Bellahcène, Castronovo
    Cells.2019; 8(9): 954.     CrossRef
  • Myoferlin, a multifunctional protein in normal cells, has novel and key roles in various cancers
    Wei Zhu, Bolun Zhou, Chenxuan Zhao, Zhengqing Ba, Hongjuan Xu, Xuejun Yan, Weidong Liu, Bin Zhu, Lei Wang, Caiping Ren
    Journal of Cellular and Molecular Medicine.2019; 23(11): 7180.     CrossRef
  • Myoferlin, a Membrane Protein with Emerging Oncogenic Roles
    Yimin Dong, Honglei Kang, Huiyong Liu, Jia Wang, Qian Guo, Chao Song, Yunlong Sun, Ya Zhang, Honghua Zhang, Zheng Zhang, Hanfeng Guan, Zhong Fang, Feng Li
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HER2 Status and Its Heterogeneity in Gastric Carcinoma of Vietnamese Patient
Dang Anh Thu Phan, Vu Thien Nguyen, Thi Ngoc Ha Hua, Quoc Dat Ngo, Thi Phuong Thao Doan, Sao Trung Nguyen, Anh Tu Thai, Van Thanh Nguyen
J Pathol Transl Med. 2017;51(4):396-402.   Published online June 19, 2017
DOI: https://doi.org/10.4132/jptm.2017.04.24
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AbstractAbstract PDF
Background
Human epidermal growth factor receptor 2 (HER2) is related to the pathogenesis and poor outcome of numerous types of carcinomas, including gastric carcinoma. Gastric cancer patients with HER2 positivity have become potential candidates for targeted therapy with trastuzumab.
Methods
We investigated 208 gastric cancer specimens using immunohistochemistry (IHC), fluorescence in situ hybridization and dual in situ hybridization (ISH). We also investigated the concordance between IHC and ISH. The correlation between HER2 status and various clinicopathological findings was also investigated.
Results
In total, 15.9% (33/208) and 24.5% (51/208) of gastric cancers showed HER2 gene amplification and protein overexpression, respectively. A high level of concordance between ISH and IHC analyses (91.3%, κ = 0.76) was found. A significant correlation between HER2 status and intestinal-type (p < .05) and differentiated carcinomas (p < .05) was also noted. The HER2 heterogeneity was high in gastric cancers; we found 68.8% phenotypic heterogeneity and 57.6% genotypic heterogeneity. Heterogeneity in HER2 protein expression and gene amplification showed a close association with diffuse histologic type and IHC 2+.
Conclusions
HER2 protein overexpression and gene amplification were detected in 24.5% and 15.9% of gastric cancer specimens, respectively. Intestinal-type showed a higher level of HER2 protein overexpression and gene amplification than diffuse type. HER2 status also showed a significant relationship with well- and moderately-differentiated carcinomas. The ratio of phenotypic and genotypic heterogeneity of HER2 was high in gastric carcinomas and was associated with HER2 IHC 2+ and diffuse histologic type.

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  • Identifying HER2 from serum‐derived exosomes in advanced gastric cancer as a promising biomarker for assessing tissue HER2 status and predicting the efficacy of trastuzumab‐based therapy
    Qian Li, Minzhi Lv, Lihua Lv, Nida Cao, Aiguang Zhao, Jiayan Chen, Xi Tang, Rongkui Luo, Shan Yu, Yan Zhou, Yuehong Cui, Wei Guo, Tianshu Liu
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    Rafid A. Abood, Saad Alomar, Sawsan S. Alharoon
    Journal of Public Health in Africa.2023;[Epub]     CrossRef
  • Receptor Tyrosine Kinases Amplified in Diffuse-Type Gastric Carcinoma: Potential Targeted Therapies and Novel Downstream Effectors
    Hideki Yamaguchi, Yuko Nagamura, Makoto Miyazaki
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    Renshen Xiang, Yuping Rong, Yuhang Ge, Wei Song, Jun Ren, Tao Fu
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    Renshen Xiang, Wei Song, Jun Ren, Jing Wu, Jincheng Fu, Tao Fu
    Stem Cell Research & Therapy.2021;[Epub]     CrossRef
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    Yoshie Kobayashi, Seung-Oe Lim, Hirohito Yamaguchi
    Seminars in Cancer Biology.2020; 65: 51.     CrossRef
  • Blockade of ITGA2 Induces Apoptosis and Inhibits Cell Migration in Gastric Cancer
    Yu-Chang Chuang, Hsin-Yi Wu, Yu-Ling Lin, Shey-Cherng Tzou, Cheng-Hsun Chuang, Ting-Yan Jian, Pin-Rong Chen, Yuan-Ching Chang, Chi-Hsin Lin, Tse-Hung Huang, Chao-Ching Wang, Yi-Lin Chan, Kuang-Wen Liao
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Implication of PHF2 Expression in Clear Cell Renal Cell Carcinoma
Cheol Lee, Bohyun Kim, Boram Song, Kyung Chul Moon
J Pathol Transl Med. 2017;51(4):359-364.   Published online June 13, 2017
DOI: https://doi.org/10.4132/jptm.2017.03.16
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AbstractAbstract PDF
Background
Clear cell renal cell carcinoma (CCRCC) is presumed to be associated with adipogenic differentiation. Histone modification is known to be important for adipogenesis, and the function of histone demethylase plant homeodomain finger 2 (PHF2) has been noted. In addition, PHF2 may act as a tumor suppressor via epigenetic regulation of p53 and is reported to be reduced in colon cancer and stomach cancer tissues. In this study, we examined PHF2 expression in CCRCC specimens by immunohistochemistry.
Methods
We studied 254 CCRCCs and 56 non-neoplastic renal tissues from patients who underwent radical or partial nephrectomy between 2000 and 2003 at the Seoul National University Hospital. Tissue microarray blocks were prepared, and immunohistochemical staining for PHF2 was performed.
Results
Among 254 CCRCC cases, 150 cases (59.1%) showed high expression and 104 cases (40.1%) showed low expression. High expression of PHF2 was significantly correlated with a low Fuhrman nuclear grade (p < .001), smaller tumor size (p < .001), low overall stage (p = .003), longer cancer-specific survival (p = .002), and progression-free survival (p < .001) of the patients. However, it was not an independent prognostic factor in multivariate analysis adjusted for Fuhrman nuclear grade and overall stage.
Conclusions
Our study showed that low expression of PHF2 is associated with aggressiveness and poor prognosis of CCRCC.

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  • The role of histone methylation in renal cell cancer: an update
    Yanguang Hou, Yan Yuan, Yanze Li, Lei Wang, Juncheng Hu, Xiuheng Liu
    Molecular Biology Reports.2023; 50(3): 2735.     CrossRef
  • Phosphorylation of PHF2 by AMPK releases the repressive H3K9me2 and inhibits cancer metastasis
    Ying Dong, Hao Hu, Xuan Zhang, Yunkai Zhang, Xin Sun, Hanlin Wang, Weijuan Kan, Min-jia Tan, Hong Shi, Yi Zang, Jia Li
    Signal Transduction and Targeted Therapy.2023;[Epub]     CrossRef
  • HIF-1α-mediated augmentation of miRNA-18b-5p facilitates proliferation and metastasis in osteosarcoma through attenuation PHF2
    Peng Luo, Yan-dong Zhang, Feng He, Chang-jun Tong, Kai Liu, He Liu, Shi-zhuang Zhu, Jian-zhou Luo, Bing Yuan
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    Reza Panahi, Esmaeil Ebrahimie, Ali Niazi, Alireza Afsharifar
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  • PHF2 regulates homology-directed DNA repair by controlling the resection of DNA double strand breaks
    Ignacio Alonso-de Vega, Maria Cristina Paz-Cabrera, Magdalena B Rother, Wouter W Wiegant, Cintia Checa-Rodríguez, Juan Ramón Hernández-Fernaud, Pablo Huertas, Raimundo Freire, Haico van Attikum, Veronique A J Smits
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    Sarder Arifuzzaman, Mst Reshma Khatun, Rabeya Khatun
    Biomedicine & Pharmacotherapy.2020; 129: 110392.     CrossRef
  • Biology and targeting of the Jumonji-domain histone demethylase family in childhood neoplasia: a preclinical overview
    Tyler S. McCann, Lays M. Sobral, Chelsea Self, Joseph Hsieh, Marybeth Sechler, Paul Jedlicka
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  • MiR-221 Promotes Hepatocellular Carcinoma Cells Migration via Targeting PHF2
    Yi Fu, Mingyan Liu, Fengxia Li, Li Qian, Ping Zhang, Fengwei Lv, Wenting Cheng, Ruixing Hou
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  • PHF2 histone demethylase prevents DNA damage and genome instability by controlling cell cycle progression of neural progenitors
    Stella Pappa, Natalia Padilla, Simona Iacobucci, Marta Vicioso, Elena Álvarez de la Campa, Claudia Navarro, Elia Marcos, Xavier de la Cruz, Marian A. Martínez-Balbás
    Proceedings of the National Academy of Sciences.2019; 116(39): 19464.     CrossRef
  • Plant homeodomain finger protein 2 as a novel IKAROS target in acute lymphoblastic leukemia
    Zheng Ge, Yan Gu, Qi Han, Justin Sloane, Qinyu Ge, Goufeng Gao, Jinlong Ma, Huihui Song, Jiaojiao Hu, Baoan Chen, Sinisa Dovat, Chunhua Song
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Yes-Associated Protein Expression Is Correlated to the Differentiation of Prostate Adenocarcinoma
Myung-Giun Noh, Sung Sun Kim, Eu Chang Hwang, Dong Deuk Kwon, Chan Choi
J Pathol Transl Med. 2017;51(4):365-373.   Published online June 9, 2017
DOI: https://doi.org/10.4132/jptm.2017.05.04
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AbstractAbstract PDF
Background
Yes-associated protein (YAP) in the Hippo signaling pathway is a growth control pathway that regulates cell proliferation and stem cell functions. Abnormal regulation of YAP was reported in human cancers including liver, lung, breast, skin, colon, and ovarian cancer. However, the function of YAP is not known in prostate adenocarcinoma. The purpose of this study was to investigate the role of YAP in tumorigenesis, differentiation, and prognosis of prostate adenocarcinoma.
Methods
The nuclear and cytoplasmic expression of YAP was examined in 188 cases of prostate adenocarcinoma using immunohistochemistry. YAP expression levels were evaluated in the nucleus and cytoplasm of the prostate adenocarcinoma and the adjacent normal prostate tissue. The presence of immunopositive tumor cells was evaluated and interpreted in comparison with the patients’ clinicopathologic data.
Results
YAP expression levels were not significantly different between normal epithelial cells and prostate adenocarcinoma. However, YAP expression level was significantly higher in carcinomas with a high Gleason grades (8–10) than in carcinomas with a low Gleason grades (6–7) (p < .01). There was no statistical correlation between YAP expression and stage, age, prostate-specific antigen level, and tumor volume. Biochemical recurrence (BCR)–free survival was significantly lower in patients with high YAP expressing cancers (p = .02). However high YAP expression was not an independent prognostic factor for BCR in the Cox proportional hazards model.
Conclusions
The results suggested that YAP is not associated with prostate adenocarcinoma development, but it may be associated with the differentiation of the adenocarcinoma. YAP was not associated with BCR.

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    Rui-Yu Weng, Lei Zhang, Ji-Long Liu
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    Ishita Ghosh, Md Imtiaz Khalil, Rusella Mirza, Judy King, Damilola Olatunde, Arrigo De Benedetti
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    Jiliang Feng, Dawei Zhao, Fudong Lv, Zhongyu Yuan
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  • A Yes-Associated Protein (YAP) and Insulin-Like Growth Factor 1 Receptor (IGF-1R) Signaling Loop Is Involved in Sorafenib Resistance in Hepatocellular Carcinoma
    Mai-Huong T. Ngo, Sue-Wei Peng, Yung-Che Kuo, Chun-Yen Lin, Ming-Heng Wu, Chia-Hsien Chuang, Cheng-Xiang Kao, Han-Yin Jeng, Gee-Way Lin, Thai-Yen Ling, Te-Sheng Chang, Yen-Hua Huang
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Basaloid Squamous Cell Carcinoma of the Head and Neck: Subclassification into Basal, Ductal, and Mixed Subtypes Based on Comparison of Clinico-pathologic Features and Expression of p53, Cyclin D1, Epidermal Growth Factor Receptor, p16, and Human Papillomavirus
Kyung-Ja Cho, Se Un Jeong, Sung Bae Kim, Sang-wook Lee, Seung-Ho Choi, Soon Yuhl Nam, Sang Yoon Kim
J Pathol Transl Med. 2017;51(4):374-380.   Published online June 8, 2017
DOI: https://doi.org/10.4132/jptm.2017.03.03
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  • 11 Crossref
AbstractAbstract PDF
Background
Basaloid squamous cell carcinoma (BSCC) is a rare variant of squamous cell carcinoma with distinct pathologic characteristics. The histogenesis of BSCC is not fully understood, and the cancer has been suggested to originate from a totipotent primitive cell in the basal cell layer of the surface epithelium or in the proximal duct of secretory glands.
Methods
Twenty-six cases of head and neck BSCC from Asan Medical Center, Seoul, Korea, reported during a 14-year-period were subclassified into basal, ductal, and mixed subtypes according to the expression of basal (cytokeratin [CK] 5/6, p63) or ductal markers (CK7, CK8/18). The cases were also subject to immunohistochemical study for CK19, p53, cyclin D1, epidermal growth factor receptor (EGFR), and p16 and to in situ hybridization for human papillomavirus (HPV), and the results were clinico-pathologically compared.
Results
Mixed subtype (12 cases) was the most common, and these cases showed hypopharyngeal predilection, older age, and higher expression of CK19, p53, and EGFR than other subtypes. The basal subtype (nine cases) showed frequent comedo-necrosis and high expression of cyclin D1. The ductal subtype (five cases) showed the lowest expression of p53, cyclin D1, and EGFR. A small number of p16- and/or HPV-positive cases were not restricted to one subtype. BSCC was the cause of death in 19 patients, and the average follow-up period for all patients was 79.5 months. Overall survival among the three subtypes was not significantly different.
Conclusions
The results of this study suggest a heterogeneous pathogenesis of head and neck BSCC. Each subtype showed variable histology and immunoprofiles, although the clinical implication of heterogeneity was not determined in this study.

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