- Association between p53 Expression and Amount of Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer
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Miseon Lee, In Ah Park, Sun-Hee Heo, Young-Ae Kim, Gyungyub Gong, Hee Jin Lee
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J Pathol Transl Med. 2019;53(3):180-187. Published online March 11, 2019
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DOI: https://doi.org/10.4132/jptm.2019.02.08
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Abstract
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- Background
Most triple-negative breast cancers (TNBCs) have a high histologic grade, are associated with high endoplasmic stress, and possess a high frequency of TP53 mutations. TP53 missense mutations lead to the production of mutant p53 protein and usually show high levels of p53 protein expression. Tumor-infiltrating lymphocytes (TILs) accumulate as part of the anti-tumor immune response and have a strong prognostic and predictive significance in TNBC. We aimed to elucidate the association between p53 expression and the amount of TILs in TNBC.
Methods In 678 TNBC patients, we evaluated TIL levels and expression of endoplasmic stress molecules. Immunohistochemical examination of p53 protein expression was categorized into three groups: no, low, and high expression.
Results No, low, and high p53 expression was identified in 44.1% (n = 299), 20.1% (n = 136), and 35.8% (n = 243) of patients, respectively. Patients with high p53 expression showed high histologic grade (p < .001), high TIL levels (p = .009), and high expression of endoplasmic reticulum stress-associated molecules (p-eIF2a, p = .013; XBP1, p = .007), compared to patients with low p53 expression. There was no significant difference in disease-free (p = .406) or overall survival rates (p = .444) among the three p53 expression groups.
Conclusions High p53 expression is associated with increased expression of endoplasmic reticulum stress molecules and TIL influx.
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Citations
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- The search for a TNBC vaccine: the guardian vaccine
Cory Fines, Helen McCarthy, Niamh Buckley Cancer Biology & Therapy.2025;[Epub] CrossRef - Correlating p53 immunostaining patterns with somatic TP53 mutation and functional properties of mutant p53 in triple‐negative breast cancer
Meejeong Kim, Miseon Lee, Ahwon Lee, Byung‐Ock Choi, Woo‐Chan Park, Sung Hun Kim, Jieun Lee, Jun Kang Histopathology.2025;[Epub] CrossRef - Updated Austrian treatment algorithm for metastatic triple-negative breast cancer
Rupert Bartsch, Gabriel Rinnerthaler, Edgar Petru, Daniel Egle, Michael Gnant, Marija Balic, Thamer Sliwa, Christian Singer Wiener klinische Wochenschrift.2024; 136(11-12): 347. CrossRef - Triple negative breast cancer: Immunogenicity, tumor microenvironment, and immunotherapy
Sotiris Loizides, Anastasia Constantinidou Frontiers in Genetics.2023;[Epub] CrossRef - Prognostic benefit of TILs independent of clinicopathological and molecular factors
Koen Brummel, Anneke L. Eerkens, Marco de Bruyn, Hans W. Nijman British Journal of Cancer.2023; 129(5): 737. CrossRef - Dihydroartemisinin-Transferrin Adducts Enhance TRAIL-Induced Apoptosis in Triple-Negative Breast Cancer in a P53-Independent and ROS-Dependent Manner
Xinyu Zhou, Abel Soto-Gamez, Fleur Nijdam, Rita Setroikromo, Wim J. Quax Frontiers in Oncology.2022;[Epub] CrossRef - New Challenges in the Differential Diagnosis of High-Grade Triple-Negative Breast Cancer and Serous Carcinoma
Andrii Puzyrenko, Chandler S Cortina, Julie M Jorns International Journal of Surgical Pathology.2022; 30(7): 728. CrossRef - Prognostic analysis of cuproptosis-related gene in triple-negative breast cancer
Shengnan Sha, Luyi Si, Xinrui Wu, Yuanbiao Chen, Hui Xiong, Ying Xu, Wangrui Liu, Haijun Mei, Tao Wang, Mei Li Frontiers in Immunology.2022;[Epub] CrossRef - p53 Missense Mutation is Associated with Immune Cell PD-L1 Expression in Triple-Negative Breast Cancer
Ai-Yan Xing, Long Liu, Ke Liang, Bin Wang Cancer Investigation.2022; 40(10): 879. CrossRef - Crosstalk between Immune Checkpoint Modulators, Metabolic Reprogramming and Cellular Plasticity in Triple-Negative Breast Cancer
Arpita Poddar, Sushma R. Rao, Prashanth Prithviraj, George Kannourakis, Aparna Jayachandran Current Oncology.2022; 29(10): 6847. CrossRef - The tumor microenvironment and triple-negative breast cancer aggressiveness: shedding light on mechanisms and targeting
Natsuki Furukawa, Vered Stearns, Cesar A. Santa-Maria, Aleksander S. Popel Expert Opinion on Therapeutic Targets.2022; 26(12): 1041. CrossRef - Intracellular partners of fibroblast growth factors 1 and 2 - implications for functions
Katarzyna Dominika Sluzalska, Jakub Slawski, Martyna Sochacka, Agata Lampart, Jacek Otlewski, Malgorzata Zakrzewska Cytokine & Growth Factor Reviews.2021; 57: 93. CrossRef - Targeted Chinese Medicine Delivery by A New Family of Biodegradable Pseudo-Protein Nanoparticles for Treating Triple-Negative Breast Cancer: In Vitro and In Vivo Study
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Marie Colombe Agahozo, Marcel Smid, Ronald van Marion, Dora Hammerl, Thierry P. P. van den Bosch, Mieke A. M. Timmermans, Chayenne J. Heijerman, Pieter J. Westenend, Reno Debets, John W. M. Martens, Carolien H. M. van Deurzen Biology.2021; 10(8): 768. CrossRef - With Our Powers Combined
Lawrence Kasherman, Katherine Karakasis, Amit M. Oza The Cancer Journal.2021; 27(6): 511. CrossRef The Research Progress on the Prognostic Value of the Common Hematological Parameters in Peripheral Venous Blood in Breast Cancer Li Chen, Xiangyi Kong, Chengrui Yan, Yi Fang, Jing Wang OncoTargets and Therapy.2020; Volume 13: 1397. CrossRefBiomolecular Factors Represented by Bcl-2, p53, and Tumor-Infiltrating Lymphocytes Predict Response for Adjuvant Anthracycline Chemotherapy in Patients with Early Triple-Negative Breast Cancer Xenia Elena Bacinschi, Anca Zgura, Inga Safta, Rodica Anghel Cancer Management and Research.2020; Volume 12: 11965. CrossRef
- A Pyloric Gland-Phenotype Ovarian Mucinous Tumor Resembling Lobular Endocervical Glandular Hyperplasia in a Patient with Peutz-Jeghers Syndrome
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Eun Na Kim, Gu-Hwan Kim, Jiyoon Kim, In Ah Park, Jin Ho Shin, Yun Chai, Kyu-Rae Kim
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J Pathol Transl Med. 2017;51(2):159-164. Published online August 22, 2016
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DOI: https://doi.org/10.4132/jptm.2016.07.01
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8,817
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Abstract
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- We describe an ovarian mucinous neoplasm that histologically resembles lobular endocervical glandular hyperplasia (LEGH) containing pyloric gland type mucin in a patient with Peutz-Jeghers syndrome (PJS). Although ovarian mucinous tumors rarely occur in PJS patients, their pyloric gland phenotype has not been clearly determined. The histopathologic features of the ovarian mucinous tumor were reminiscent of LEGH. The cytoplasmic mucin was stained with periodic acid-Schiff reaction after diastase treatment but was negative for Alcian blue pH 2.5, suggesting the presence of neutral mucin. Immunohistochemically, the epithelium expressed various gastric markers, including MUC6, HIK1083, and carbonic anhydrase-IX. Multiple ligation-dependent probe amplification detected a germline heterozygous deletion mutation at exons 1–7 of the STK11 gene (c.1-?_920+?del) in peripheral blood leukocytes and mosaic loss of heterozygosity in ovarian tumor tissue. Considering that LEGH and/or gastric-type cervical adenocarcinoma can be found in patients with PJS carrying germline and/or somatic STK11 mutations, our case indicates that STK11 mutations have an important role in the proliferation of pyloric-phenotype mucinous epithelium at various anatomical locations.
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Citations
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- Serine/threonine kinase 11 (STK11) associated adnexal tumors: from biology to therapeutic impact
Guanxiang Huang, Wenyu Lin, Tingting Jiang, Yuanjun Cai, Chengbin Lin, Pengming Sun Human Genomics.2025;[Epub] CrossRef - Ovarian Mucinous Tumor Presenting Atypical Lobular Endocervical Glandular Hyperplasia-Like Appearance in a Patient With Germline STK11 p.F354L Variant: A Case Report
Hiroshi Yoshida, Kengo Hiranuma, Mariko Nakahara, Mayumi Kobayashi-Kato, Yasuhito Tanase, Masaya Uno, Kouya Shiraishi, Mitsuya Ishikawa, Tomoyasu Kato International Journal of Surgical Pathology.2024; 32(2): 394. CrossRef - Preoperative multimodal ultrasonic imaging in a case of Peutz-Jeghers syndrome complicated by atypical lobular endocervical glandular hyperplasia: a case report and literature review
Liwen Yang, Duan Duan, Ying Xiong, Tianjiao Liu, Lijun Zhao, Fan Lai, Dingxian Gu, Liuying Zhou Hereditary Cancer in Clinical Practice.2024;[Epub] CrossRef - Gastric‐type glandular lesions of the female genital tract excluding the cervix: emerging pathological entities
Richard W‐C Wong, Karen L Talia, W Glenn McCluggage Histopathology.2024; 85(1): 20. CrossRef - Gastric-phenotype Mucinous Carcinoma of the Fallopian Tube with Secondary Ovarian Involvement in a Woman with Peutz-Jeghers Syndrome: A Case Report
Mónica Bronte Anaut, Javier Arredondo Montero, Maria Pilar Fernández Seara, Rosa Guarch Troyas International Journal of Surgical Pathology.2023; 31(1): 92. CrossRef - Molecular characterization of gastric-type endocervical adenocarcinoma using next-generation sequencing
Swati Garg, Teddy S. Nagaria, Blaise Clarke, Orit Freedman, Zanobia Khan, Joerg Schwock, Marcus Q. Bernardini, Amit M. Oza, Kathy Han, Adam C. Smith, Tracy L. Stockley, Marjan Rouzbahman Modern Pathology.2019; 32(12): 1823. CrossRef - The developing spectrum of gastric-type cervical glandular lesions
Karen L. Talia, W. Glenn McCluggage Pathology.2018; 50(2): 122. CrossRef
- Diagnostic Significance of Cellular Neuroglial Tissue in Ovarian Immature Teratoma
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Yun Chai, Chang Gok Woo, Joo-Young Kim, Chong Jai Kim, Shin Kwang Khang, Jiyoon Kim, In Ah Park, Eun Na Kim, Kyu-Rae Kim
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J Pathol Transl Med. 2017;51(1):49-55. Published online October 14, 2016
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DOI: https://doi.org/10.4132/jptm.2016.09.19
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Abstract
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- Background
Immature teratoma (IT) is a tumor containing immature neuroectodermal tissue, primarily in the form of neuroepithelial tubules. However, the diagnosis of tumors containing only cellular neuroglial tissue (CNT) without distinct neuroepithelial tubules is often difficult, since the histological characteristics of immature neuroectodermal tissues remain unclear. Here, we examined the significance of CNT and tried to define immature neuroectodermal tissues by comparing the histological features of neuroglial tissues between mature teratoma (MT) and IT.
Methods The histological features of neuroglial tissue, including the cellularity, border between the neuroglial and adjacent tissues, cellular composition, mitotic index, Ki-67 proliferation rate, presence or absence of tissue necrosis, vascularity, and endothelial hyperplasia, were compared between 91 MT and 35 IT cases.
Results CNTs with a cellularity grade of ≥ 2 were observed in 96% of IT cases and 4% of MT cases (p < .001); however, CNT with a cellularity grade of 3 in MT cases was confined to the histologically distinct granular layer of mature cerebellar tissue. Moreover, CNT in IT exhibited significantly higher rates of Ki-67 proliferation, mitoses, and necrosis than those in MT (p < .001). Furthermore, an infiltrative border of neuroglial tissue and glomeruloid endothelial hyperplasia were significantly more frequent in IT cases than in MT cases (p < .001).
Conclusions Our results suggest that if CNT with a cellularity grade of ≥ 2 is not a component of cerebellar tissue, such cases should be diagnosed as IT containing immature neuroectodermal tissue, particularly if they exhibit an infiltrative border, mitoses, necrosis, and increased Ki-67 proliferation.
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Citations
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- An Atypical Presentation of a Pediatric Mature Teratoma: A Case Report and Review of the Literature
Ahmed M Othman, Abdulaziz A Abu Alnasr, Reem E Kordi, Shahad A Abu Alnasr Cureus.2024;[Epub] CrossRef - Immature Teratoma: Diagnosis and Management—A Review of the Literature
Liviu Moraru, Melinda-Ildiko Mitranovici, Diana Maria Chiorean, Marius Coroș, Raluca Moraru, Ioan Emilian Oală, Sabin Gligore Turdean Diagnostics.2023; 13(9): 1516. CrossRef - Congenital Immature Grade ΙΙΙ Teratoma of the Neck: A Case Report
Nazneen Liaqat, Israr Ud Din, Zeeshan Ali, Majid Rashid, Afsheen Liaqat Cureus.2023;[Epub] CrossRef - Benign ovarian teratoma in the dog with predominantly nervous tissue: A case report
P Makovicky, AV Makarevich, P Makovicky, A Seidavi, L Vannucci, K Rimarova Veterinární medicína.2022; 67(2): 99. CrossRef - Fascin as a Useful Marker for Identifying Neural Components in Immature Teratomas of Human Ovary and Those Derived From Murine Embryonic Stem Cells
Ryunosuke Umehara, Atsushi Kurata, Masakatsu Takanashi, Hirotsugu Hashimoto, Koji Fujita, Toshitaka Nagao, Masahiko Kuroda International Journal of Gynecological Pathology.2019; 38(4): 377. CrossRef - Cerebellar Differentiation in Ovarian Teratoma: A Report of 6 Cases
Colin J.R. Stewart, Maxine L. Crook International Journal of Gynecological Pathology.2018; 37(4): 316. CrossRef - Mitotic activity of epithelia of ectoand entodermal types in spontaneous and experimental teratomas of mice
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