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p16, MDM2

Nicole E McNeil, Hesed M Padilla-Nash, Floryne O Buishand, Yue Hue, Thomas Ried
Human colorectal carcinomas are defined by a non-random 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...
October 17, 2016: 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. To assess the utility of p16 IHC in the differential diagnosis of ALT/WDLPS and DDLPS. Our series included 101 tumors that were previously analyzed using fluorescence in situ hybridization (FISH) for MDM2 and CDK4 amplification...
September 2, 2016: 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...
October 27, 2015: 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
Ali Kafadar, Özlem Küçükhüseyin, Saime Turan, Ezgi Nurdan Yenilmez, Servet Tunoglu, Umit Zeybek, Mehmet Yasar Kaynar, Rahsan Kemerdere, Ilhan Yaylim
BACKGROUND/AIM: Primary brain tumors are unique tumors due to their different pathobiological behavior, while they rarely metastasize outside the central nervous system. Regarding the oncogenesis of primary brain tumors, it was shown that changes in functions of p16 and mouse double minute 2 homolog (MDM2) are related to tumor pathogenesis by enhancing cell proliferation and malign development. The present study aims to evaluate the possible associations between cyclin-dependent kinase 2 (CDKN2) p16 540 C>G and 580 C>T, MDM2 single nucleotide polymorphism 309 (SNP309) T>G polymorphisms and primary brain tumor...
July 2015: Anticancer Research
Marie-Hélène Delfau-Larue, Wolfram Klapper, Françoise Berger, Fabrice Jardin, Josette Briere, Gilles Salles, Olivier Casasnovas, Pierre Feugier, Corinne Haioun, Vincent Ribrag, Catherine Thieblemont, Michael Unterhalt, Martin Dreyling, Elizabeth Macintyre, Christiane Pott, Olivier Hermine, Eva Hoster
We revisited the prognostic value of frequently detected somatic gene copy number alterations (CNAs) in mantle cell lymphoma (MCL) patients treated first line with immunochemotherapy and autologous stem cell transplantation (ASCT), with or without high-dose cytarabine, in the randomized European MCL Younger trial. DNA extracted from tumor material of 135 patients (median age, 56 years) was analyzed by multiplex ligation-dependent probe amplification and/or quantitative multiplex polymerase chain reaction of short fluorescent fragments...
July 30, 2015: Blood
Hiroshi Okamoto, Fumiyoshi Fujishima, Takashi Kamei, Yasuhiro Nakamura, Yohei Ozawa, Go Miyata, Toru Nakano, Kazunori Katsura, Shigeo Abe, Yusuke Taniyama, Tadashi Sakurai, Jin Teshima, Makoto Hikage, Hironobu Sasano, Noriaki Ohuchi
BACKGROUND: Definitive chemoradiotherapy (dCRT) has recently become one of the most effective therapies for the treatment of esophageal squamous cell carcinoma (ESCC). However, it is also true this treatment has not been effective in all patients. Therefore, it is very important to evaluate the surrogate marker of dCRT in order to improve clinical outcomes of patients with ESCC. On the other hand, our previous study had suggested that murine double minute 2 (MDM2) and p16 were associated with chemoradioresistance in ESCC...
2015: BMC Cancer
Louis Tsun Cheung Chow
Infiltrating angiolipoma and osteolipoma of the hand are rare. A 40-year-old man presented with slowly enlarging swelling of his right hand for two and half years without functional deficit but it became painful with slight limitation of movement for the past few months. Plain radiograph showed a large soft tissue swelling with specks of calcifications. Ultrasonography and magnetic resonance imaging revealed an infiltrative mass in the right palm deep to the flexor tendons. As biopsy suggested infiltrative angiolipoma of skeletal muscle, debulking of the tumor was performed...
June 2015: Pathology, Research and Practice
C E Boudreau, D York, R J Higgins, R A LeCouteur, P J Dickinson
In this study, we determined the expression of key signalling pathway proteins TP53, MDM2, P21, AKT, PTEN, RB1, P16, MTOR and MAPK in canine gliomas using western blotting. Protein expression was defined in three canine astrocytic glioma cell lines treated with CCNU, temozolamide or CPT-11 and was further evaluated in 22 spontaneous gliomas including high and low grade astrocytomas, high grade oligodendrogliomas and mixed oligoastrocytomas. Response to chemotherapeutic agents and cell survival were similar to that reported in human glioma cell lines...
March 25, 2015: Veterinary and Comparative Oncology
Simion I Chiosea, Lindsay Williams, Christopher C Griffith, Lester D R Thompson, Ilan Weinreb, Julie E Bauman, Alyssa Luvison, Somak Roy, Raja R Seethala, Marina N Nikiforova
Contemporary classification and treatment of salivary duct carcinoma (SDC) require its thorough molecular characterization. Thirty apocrine SDCs were analyzed by the Ion Ampliseq Cancer HotSpot panel v2 for mutations in 50 cancer-related genes. Mutational findings were corroborated by immunohistochemistry (eg, TP53, BRAF, β-catenin, estrogen, and androgen receptors) or Sanger sequencing/SNaPshot polymerase chain reaction. ERBB2 (HER2), PTEN, FGFR1, CDKN2A/P16, CMET, EGFR, MDM2, and PIK3CA copy number changes were studied by fluorescence in situ hybridization...
June 2015: American Journal of Surgical Pathology
Arjen H G Cleven, Evita Zwartkruis, Pancras C W Hogendoorn, Herman M Kroon, Inge Briaire-de Bruijn, Judith V M G Bovée
AIMS: Periosteal chondrosarcoma is a rare, malignant cartilage-forming neoplasm originating from the periosteal surface of bone. We collected 38 cases from the archives of the Netherlands Committee on Bone Tumours, with the aim of studying histological features and evaluating the involvement of isocitrate dehydrogenase 1 (IDH1), EXT, Wnt/β-catenin, the pRB pathway (CDK4 and p16), and the TP53 pathway (p53 and MDM2). METHODS AND RESULTS: Histology showed a moderately cellular matrix with mucoid-myxoid changes and, in 42% of cases, formation of a neocortex...
October 2015: Histopathology
Andreas Knopf, Justine Lempart, Murat Bas, Julia Slotta-Huspenina, Naglaa Mansour, Marie Kristin Fritsche
OBJECTIVES: The occurrence of squamous cell carcinoma of the tongue (SCCT) of young patients increased. There are still controversies about patient prognosis. The underlying molecular mechanisms remain unclear. METHODS: 276 patients (66 ≤45, 210 >45 years) with SCCT were included. Clinical parameters and survival data were assessed. Oncogenes and tumor suppressors were analyzed via immunohistochemistry (p53, CXCR4, p16, EGFR) and qPCR (CDK4, CDKN2A, TP53, MDM2, AKT1, PIK3CA, NRAS, HRAS, KRAS, HGF, MET, EGF, ATM, BRCA1, E2F1, FHIT, RUNX3, STK11, BCL2, CTNNB1)...
February 20, 2015: Oncotarget
Belinda Lee, Shahneen Sandhu, Grant McArthur
PURPOSE OF REVIEW: This review highlights recent clinical developments in the therapeutic targeting of cell cycle control in melanoma with cyclin-dependent kinase inhibitors, checkpoint kinases, MDM2, MDM4 and p53 inhibitors. RECENT FINDINGS: The high prevalence of activating genetic aberrations along the p16 INK4A:cyclinD-CDK4/6:RB pathway in melanoma and increasing evidence that alterations in this pathway are linked to melanomagenesis, make targeting the p16 INK4A:cyclinD-CDK4/6:RB pathway in melanoma logical and highly attractive...
March 2015: Current Opinion in Oncology
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