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p16, MDM2

Ran Peng, Huijiao Chen, Xuantao Yang, Xianliang Zhang, Zhang Zhang, Xin He, Hongying Zhang
Atypical lipomatous tumor/well-differentiated liposarcoma/dedifferentiated liposarcoma (ALT/WDL/DDL) is a common type of liposarcoma in late adulthood. However, pediatric ALT/WDL/DDL is extremely rare, and only 3 cases have been described in children younger than 10years of age. Notably, none of these cases harbored MDM2 gene amplification. Here, we reported a sclerosing ALT/WDL in a 7-year-old Chinese girl. Histologically, in most areas, the neoplastic cells were embedded within the collagenous background and typical lipogenic areas were inconspicuous throughout the sclerotic areas...
July 10, 2017: Human Pathology
Hao Sun, Jian-Xiang Shi, Hong-Fei Zhang, Meng-Tao Xing, Pei Li, Li-Ping Dai, Cheng-Lin Luo, Xiao Wang, Peng Wang, Hua Ye, Liu-Xia Li, Jian-Ying Zhang
In this study, enzyme-linked immunosorbent assay has been used to examine the frequencies of serum autoantibodies against two candidate tumor-associated antigens intensively selected from the Human Protein Atlas database, in combination with 13 tumor-associated antigens available from our lab in sera from 44 OC patients and 50 normal healthy controls. Conventional evaluation (mean + 3SD as the cutoff value to determine a positive reactivity), receiver operating characteristic curve analyses, and classification tree analysis were further used to evaluate the diagnostic performance of autoantibodies against these tumor-associated antigens (anti-tumor-associated antigens) in ovarian cancer...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Yuichi Yamada, Izumi Kinoshita, Kenichi Kohashi, Hidetaka Yamamoto, Yuki Kuma, Takamichi Ito, Kenji Koda, Atsushi Kisanuki, Manabu Kurosawa, Michiko Yoshimura, Masutaka Furue, Yoshinao Oda
Ischemic fasciitis is a benign myofibroblastic lesion, occurring in the sacral region or proximal thigh of elderly or bedridden individuals. The pathogenesis of ischemic fasciitis is thought to be based on ischemic condition; however, it has never been demonstrated. In this study, we examined the expression of ischemia-associated proteins in ischemic fasciitis by immunohistochemical and genetic methods. Specifically, this study aimed to reveal the expression of HIF-1α, MDM2, CDK4, p16, and gene amplification of MDM2 gene...
May 6, 2017: Virchows Archiv: An International Journal of Pathology
Seda Turgut, Muzaffer Ilhan, Saime Turan, Ozcan Karaman, Ilhan Yaylim, Ozlem Kucukhuseyin, Ertugrul Tasan
AIM: Prolactinomas are thought to arise from clonal expansion of a single mutated cell which is subjected to growth stimuli of several permissive factors, although the pathogenetic mechanisms underlying tumorigenesis remain unclear. The present study aimed to investigate the role of p16 (540C→G and 580C→T) and mouse double minute 2 (MDM2) (SNP309T→G) gene polymorphisms in tumorigenesis and characteristics of prolactinoma. PATIENTS AND METHODS: A total of 74 patients with prolactinoma and 100 age- and gender-matched healthy individuals were enrolled in the study...
May 2017: In Vivo
Nicolas Macagno, Stéphane Fuentes, Gonzague de Pinieux, André Maues de Paula, Sébastien Salas, Jean-Camille Mattéi, Charlotte Dupuis, Romain Appay, Alain Aurias, Henry Dufour, Dominique Figarella-Branger, Corinne Bouvier
Despite being one of the most frequent soft-tissue sarcomas, well-differentiated liposarcoma has never been reported near the spine. The authors present the case of a 67-year-old man with progressive history of back pain. Physical examination revealed a mass located within the right paravertebral muscles. MR and CT imaging showed a heavily ossified central mass surrounded by a peripheral fatty component. No connection with the underlying bone was detected on imagery and during surgery. After surgical resection, histopathological examination revealed a tumor harboring combined features of well-differentiated liposarcoma and low-grade osteosarcoma...
2017: Case Reports in Pathology
Alan Pollack, Deukwoo Kwon, Gail Walker, Li Yan Khor, Eric M Horwitz, Mark K Buyyounouski, Radka Stoyanova
Background: In prior retrospective studies, we assessed a number of prostate tumor tissue biomarkers that were associated independently with the clinical outcome of men treated with radiotherapy (RT) ± androgen deprivation therapy (ADT). In this report, the associations of selected biomarkers with biochemical or clinical disease failure (BCDF) were prospectively evaluated in men with T1-T3 prostate cancer on a randomized hypofractionation trial. Methods: Biomarkers were analyzed in 263 of 303 men randomly assigned to standard vs moderate hypofractionation...
February 1, 2017: Journal of the National Cancer Institute
M Kalim A Khan, Salman Akhtar, Jamal M Arif
In the proposed work, we have explicated the mechanism of dibenzo[a,l]pyrene (DBP) and benzo[a]pyrene (BP) modulated cell proliferation by assessing the plausible binding with CASPASES, BAX, Bcl-2, MDM2, p53, p21, p16, CylinD1-CDK4 complex, CylinE1-CDK2 complex, H-Ras, K-Ras, BRCA1, and BRCA2 through exploiting the inherent potential of AutoDock Tools 4.0. In silico findings revealed that potent carcinogenic metabolites of DBP (e.g., (-)-anti-DBPDE and (+)-syn-DBPDE) and BP (e.g., (+)-anti-BPDE) exhibited better binding interactions to Caspase-9 than Caspase-8 and Caspase-3...
April 3, 2017: Interdisciplinary Sciences, Computational Life Sciences
Ming J Poi, Junan Li, Douglas W Sborov, Zachary VanGundy, Yu Kyoung Cho, Misty Lamprecht, Flavia Pichiorri, Mitch A Phelps, Craig C Hofmeister
Multiple myeloma (MM) is a hematologic malignancy characterized by clonal proliferation of plasma cells and overproduction of monoclonal immunoglobins. Treatment with melphalan is currently standard of care for younger and fit patients when followed by hematopoietic stem cell transplantation (HSCT), and in transplant ineligible patients when used in combination regimens. It has been previously shown that changes in the p53 pathway are associated with melphalan efficacy, but the regulatory role of the p14ARF-MDM2-p53 axis has yet to be fully explored...
February 2, 2017: Molecular Carcinogenesis
Borislav A Alexiev, Yanki Tumer, Guang-Yu Yang
Diffuse-type tenosynovial giant cell tumor (D-T TSGCT) is regarded as a benign but locally aggressive neoplasm with significant recurrent potential. We report a case of malignant (D-T TSGCT with pleural metastases arising in the left knee in a 57-year-old male. The tumor demonstrated atypical features, including a solid infiltrative pattern with spindling of the tumor cells, nuclear pleomorphism with prominent nucleoli, and markedly increased mitotic activity (>20 mitoses/10 HPF). The immunoprofile demonstrated clusterin+, D2-40+, CD68+, p63+, MDM2+, p16- tumor...
December 15, 2016: Human Pathology
Nicole E McNeil, Hesed M Padilla-Nash, Floryne O Buishand, Yue Hue, Thomas Ried
Human colorectal carcinomas are defined by a nonrandom distribution of genomic imbalances that are characteristic for this disease. Often, these imbalances affect entire chromosomes. Understanding the role of these aneuploidies for carcinogenesis is of utmost importance. Currently, established transgenic mice do not recapitulate the pathognonomic genome aberration profile of human colorectal carcinomas. We have developed a novel model based on the spontaneous transformation of murine colon epithelial cells...
March 2017: Genes, Chromosomes & Cancer
Solène-Florence Kammerer-Jacquet, Sixte Thierry, Florian Cabillic, Morgane Lannes, Florence Burtin, Sébastien Henno, Frédéric Dugay, Guillaume Bouzillé, Nathalie Rioux-Leclercq, Marc-Antoine Belaud-Rotureau, Nathalie Stock
The differential diagnosis between atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDLPS) and dedifferentiated liposarcoma (DDLPS) from their morphologic counterparts is challenging. Currently, the diagnosis is guided by MDM2 and CDK4 immunohistochemistry (IHC) and is confirmed by the amplification of the corresponding genes. Recently, p16 IHC has been proposed as a useful diagnostic biomarker. The objective was to assess the utility of p16 IHC in the differential diagnosis of ALT/WDLPS and DDLPS...
January 2017: Human Pathology
Liping Dai, Jun-Chieh J Tsay, Jitian Li, Ting-An Yie, John S Munger, Harvey Pass, William N Rom, Yi Zhang, Eng M Tan, Jian-Ying Zhang
OBJECTIVES: Autoantibodies against tumor-associated antigens (TAAs) identified in patients with advanced lung cancer may be detected in subjects with early lung cancer or even predate the diagnosis. The purpose of this study is to address the temporal relationship between lung cancer development and serum autoantibody response. MATERIALS AND METHODS: Two cohorts of patients with newly diagnosed lung cancer were included. The first cohort included 90 sera from patients with lung cancer (Stages I-III) and 89 normal control sera...
September 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
I Petersen, E Wardelmann
Malignancy grading is an essential element in the classification of sarcomas. It correlates with the prognosis of the disease and the risk of metastasis. This article presents the grading schemes for soft tissue, bone and pediatric sarcomas. It summarizes the histological criteria of the Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC) system and the Pediatric Oncology Group as well as the grading of bone tumors by the College of American Pathologists (CAP). Furthermore, the potential relevance of gene expression signatures, the complexity index in sarcoma (CINSARC) and single genetic alterations (p53, MDM2, p16, SWI/SNF, EWSR1 fusions and PAX3/PAX7-FOXO1 fusions) for the prognosis of sarcomas are discussed...
July 2016: Der Pathologe
Magnus Hallin, Nina Schneider, Khin Thway
Well-differentiated liposarcoma (WDL) can show a morphologic spectrum, including lipoma-like, sclerosing and inflammatory subtypes. It does not metastasize but can dedifferentiate, acquiring metastatic potential. Hibernomas are benign neoplasms that show variable differentiation toward brown fat, and can sometimes occur in the abdomen or retroperitoneum. We illustrate a case of retroperitoneal WDL that showed extensive hibernoma-like morphology, with sheets of multivacuolated adipocytes of varying sizes, with abundant cytoplasm and numerous lipid vacuoles or granular eosinophilic cytoplasm...
October 2016: International Journal of Surgical Pathology
Yun Feng, Yuncheng Li, Yang Zhang, Hongliang Zheng, Guojun Li
OBJECTIVES: Genetic polymorphisms of genes in cell cycle, apoptosis, and inflammation/immune response pathways may control the mechanisms of HPV clearance and HPV escape of immune surveillance and thus may affect both tumor HPV16 status and possibly related outcomes of squamous cell carcinoma of the oropharynx (SCCOP) patients. MATERIALS AND METHODS: We determined tumor HPV16 status and genotyped selected polymorphisms in key genes involved in cell cycle, apoptosis, and inflammation/immune response pathways in 401 incident SCCOP patients...
May 2016: Oral Oncology
M R Sargen, S L Merrill, E Y Chu, K L Nathanson
An inherited germline mutation in CDKN2A is the most common cause of familial atypical multiple mole melanoma (FAMMM) syndrome. Although it is well known that CDKN2A mutations confer an increased risk for melanoma and pancreatic carcinoma, the association with an increased risk for nerve sheath tumours and other tumour types is under-recognized. We report a family with a missense mutation (c.151-1G>C) at the acceptor splice site of intron 1 of CDKN2A, resulting in loss of function of both tumour suppressor proteins p16(INK) (4) and p14(ARF) ...
October 2016: British Journal of Dermatology
Yuna Kang, Andrew E Horvai
Dedifferentiated liposarcoma (DDL) frequently involves the retroperitoneum. In the absence of a lipogenic component histologically, the differential diagnosis of a retroperitoneal DDL includes other sarcomas and, if the tumor has visceral involvement, sarcomatoid carcinoma. DDL demonstrates amplification of chromosome subregion 12q13-q15. Detection of the amplification itself, or the resulting overexpression of the MDM2 and CDK4 genes by genetic and immunohistochemical methods, is a useful ancillary test in the diagnosis of DDL...
January 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
Du He, Min Chen, Huijiao Chen, Dianying Liao, Xiaozhou Wang, Zhang Zhang, Hongying Zhang
Liposarcoma originating in the heart is extraordinarily rare. Herein, we report a dedifferentiated liposarcoma arising from the left atrium in a 59-year-old Chinese man. Histologically, the neoplasm predominantly consisted of undifferentiated pleomorphic sarcoma. In addition, the neoplasm exhibited lipoblastic differentiation and osteo-/chondrosarcomatous components. Immunohistochemically, the neoplastic cells were strongly positive for p16, MDM2, and CDK4. Fluorescence in situ hybridization showed MDM2 gene amplification in all of the tumor components...
2015: International Journal of Clinical and Experimental Pathology
Abbas Agaimy, Katja Specht, Robert Stoehr, Thomas Lorey, Bruno Märkl, Gerald Niedobitek, Melanie Straub, Thomas Hager, Anna-Carinna Reis, Bastian Schilling, Regine Schneider-Stock, Arndt Hartmann, Thomas Mentzel
Metastatic malignant melanoma is notorious for its phenotypic diversity and loss of differentiation markers. We herein summarized our experience with 14 metastatic melanomas showing complete loss of immunohistochemical melanocytic markers (with or without heterologous differentiation). Patients included 11 men and 3 women aged 24 to 78 years (median, 67 y). Thirteen patients had histologically confirmed primary skin melanoma, and 1 had metastatic melanoma of unknown primary. Undifferentiated metastasis was diagnosed synchronous to primary tumor (n=1), following skin melanoma by 3 months to 9 years (n=11) and preceding it by 1 year (n=1)...
February 2016: American Journal of Surgical Pathology
Wen Ng, Christina Messiou, Myles Smith, Khin Thway
Distinguishing well-differentiated liposarcoma (WDL) from lipoma is of clinical and prognostic importance, but can be difficult on imaging and histology alone. WDL characteristically harbor amplifications of the MDM2 and CDK4 cell cycle oncogenes and overexpress the cell cycle regulator p16. Fluorescence in situ hybridization (FISH) to assess for MDM2 and CDK4 gene amplification is the diagnostic gold standard, and immunohistochemistry for the overexpressed MDM2 and CDK4 proteins is also useful but may not be routinely offered by pathology laboratories...
October 2015: International Journal of Surgical Pathology
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