Overview of MDM2 and B-RAF expression in gastric lesions

dc.AffiliationOctober University for modern sciences and Arts (MSA)
dc.contributor.authorAboushousha T.
dc.contributor.authorHelal N.
dc.contributor.authorHammam O.
dc.contributor.authorIbrahim M.
dc.contributor.authorKhaled S.
dc.contributor.authorMostafa A.
dc.contributor.authorAnas A.
dc.contributor.otherDepartment of Pathology
dc.contributor.otherTheodor Bilharz Research Institute
dc.contributor.otherImbaba
dc.contributor.otherGiza
dc.contributor.otherEgypt; Faculty of Biotechnology
dc.contributor.otherOctober University of Modern Sciences and Arts
dc.contributor.otherGiza
dc.contributor.otherEgypt; Department of Surgery
dc.contributor.otherTheodor Bilharz Research Institute
dc.contributor.otherImbaba
dc.contributor.otherGiza
dc.contributor.otherEgypt; Department of Hepato-Gastroenterology
dc.contributor.otherTheodor Bilharz Research Institute
dc.contributor.otherGiza
dc.contributor.otherEgypt
dc.date.accessioned2020-01-09T20:41:02Z
dc.date.available2020-01-09T20:41:02Z
dc.date.issued2018
dc.descriptionScopus
dc.description.abstractBACKGROUND: Globally, gastric cancer (GC) it is the fourth most common cancer and the third cause of cancer-related deaths. Overexpression of MDM2 and B-RAF appeared to be increased in malignancy and associated with poor prognosis in several human tumours, but their role in gastric cancer remains controversial. AIM: We had investigated the immunohistochemical expression of MDM2 and B-RAF in 136 gastric lesions with/without H. pylori association. MATERIAL AND METHODS: Studied specimens include chronic gastritis (32), intestinal type GC (70), diffuse GC (22) and gastrointestinal stromal tumours (GIST) (12). RESULTS: MDM2 expression increased significantly in intestinal GC compared to other groups (p < 0.001), while B-RAF expression increased significantly in GIST compared to other groups (p < 0.001). H. pylori increased expression of MDM2 in intestinal GC cases but did not affect B-RAF expression. MDM2 expression correlated with high grade of tumor differentiation (p < 0.001), deep invasion (p < 0.05), nodal metastases (p < 0.05) and distant metastases (p < 0.1) in intestinal GC, while B-RAF expression did not correlate with TNM stage (p < 0.1). CONCLUSION: MDM2 up-regulation was more frequent in intestinal GC, while B-RAF up-regulation was more frequent in GIST compared to other groups; MDM2 expression in intestinal GC was correlated with H. pylori association, high grade of differentiation, deep invasion, nodal and distant metastases, meanwhile, B-RAF expression was correlated with high-grade intestinal GC but did not correlate with H. pylori or TNM stage. The possible role of both MDM2 and B-RAF in predicting progression of gastric tumours and prognosis deserves further investigations. 2018 Tarek Aboushousha, Noha Helal, Olfat Hammam, Manar Ibrahim, Samar Khaled, Amr Mostafa, Amgad Anas.en_US
dc.description.urihttps://www.scimagojr.com/journalsearch.php?q=21100824403&tip=sid&clean=0
dc.identifier.doihttps://doi.org/10.3889/oamjms.2018.338
dc.identifier.issn18579655
dc.identifier.otherhttps://doi.org/10.3889/oamjms.2018.338
dc.identifier.urihttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6236038/
dc.language.isoEnglishen_US
dc.publisherSpringer
dc.publisherOpen Access Macedonian Journal of Medical Sciencesen_US
dc.relation.ispartofseriesOpen Access Macedonian Journal of Medical Sciences
dc.relation.ispartofseries6
dc.subjectOctober University for Modern Sciences and Arts
dc.subjectجامعة أكتوبر للعلوم الحديثة والآداب
dc.subjectUniversity of Modern Sciences and Arts
dc.subjectMSA University
dc.subjectB-RAFen_US
dc.subjectGastric canceren_US
dc.subjectGastritisen_US
dc.subjectH. pylorien_US
dc.subjectMDM2en_US
dc.subjectB Raf kinaseen_US
dc.subjectprotein MDM2en_US
dc.subjectArticleen_US
dc.subjectchronic gastritisen_US
dc.subjectdistant metastasisen_US
dc.subjectfemaleen_US
dc.subjectgastrointestinal stromal tumoren_US
dc.subjectHelicobacter pylorien_US
dc.subjecthumanen_US
dc.subjecthuman tissueen_US
dc.subjectimmunohistochemistryen_US
dc.subjectmaleen_US
dc.subjectprotein expressionen_US
dc.subjectstomach lesionen_US
dc.subjectstomach tumoren_US
dc.subjecttumor differentiationen_US
dc.titleOverview of MDM2 and B-RAF expression in gastric lesionsen_US
dc.typeArticleen_US
dcterms.isReferencedByFerlay, J., Soerjomataram, I., Dikshit, R., Eser, S., Mathers, C., Rebelo, M., Parkin, D.M., Bray, F., Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012 (2015) Int J Cancer, 136 (5), pp. E359-E386. , https://doi.org/10.1002/ijc.29210, 25220842; Ferro, A., Peleteiro, B., Malvezzic, M., Bosetti, C., Bertuccio, P., Levi, F., Negri, E., Lunet, N., Worldwide trends in gastric cancer mortality (1980�2011), with predictions to 2015, and incidence by subtype (2014) Eur J Cancer, 50, pp. 1330-1344. , https://doi.org/10.1016/j.ejca.2014.01.029, 24650579; Monograph of the Incidence of Gastric Carcinoma in Middle East: Middle East Cancer Consortium (MECC), , http://www.cancer.gov/cancertopics/pdq/treatment/gastric/HealthProfessional/page4#Reference4.1, accessed on 2014 Jan 10; Parkin, D.M., The global health burden of infection-associated cancers in the year 2002 (2006) International Journal of Cancer, 118 (12), pp. 3030-3044. , https://doi.org/10.1002/ijc.21731, 16404738; Poteca, T., Poteca, A., Sajin, M., Comanescu, M., Biological prognostic parameters in gastric carcinomas (2014) Chirurgia (Bucur), 109 (3), pp. 347-354; Mohammad, M.A., Hussein, L., Coward, A., Jackson, S.J., Prevalence of Helicobacter pylori infection among Egyptian children: Impact of social background and effect on growth (2008) Public Health Nutr, 11 (3), pp. 230-236. , https://doi.org/10.1017/S1368980007000481, 17666124; Estimated Cancer Incidence, Mortality and Prevalence Worldwide 2012, , http://globocan.iarc.fr/Pages/fact_sheets_population.aspx, Population fact sheets, Egypt; Oliner, J.D., Kinzler, K.W., Melzer, P.S., George, D., Vogelstein, B., Amplification of a gene encoding a p53-associated protein in human sarcomas (1992) Nature, 358, pp. 80-83. , https://doi.org/10.1038/358080a0, 1614537; Moll, U.M., Petrenko, O., The MDM2-p53 interaction (2003) Mol Cancer Res, 1, pp. 1001-1008; Li, Q., Lozano, G., Molecular pathways: Targeting Mdm2 and Mdm4 in cancer therapy (2013) Clin Cancer Res, 19, pp. 34-41. , https://doi.org/10.1158/1078-0432.CCR-12-0053, 23262034, PMC3537867; Peng, Q., Lao, X., Chen, Z., Lai, H., Deng, Y., Wang, J., Mo, C., Li, S., TP53 and MDM2 gene polymorphisms, gene-gene interaction, and hepatocellular carcinoma risk: Evidence from an updated meta-analysis (2013) Plos One, 8. , https://doi.org/10.1371/journal.pone.0082773, 24376578, PMC3871586; Park, H.S., Park, J.M., Park, S., Cho, J., Kim, S.I., Park, B.W., Subcellular localization of Mdm2 expression and prognosis of breast cancer (2014) Int J Clin Oncol, 19 (5), pp. 842-851. , https://doi.org/10.1007/s10147-013-0639-1, 24292333; Rahman, M.A., Salajegheh, A., Smith, R.A., Lam, A.K., B-Raf mutation: A key player in molecular biology of cancer (2013) Exp Mol Pathol, 95, pp. 336-342. , https://doi.org/10.1016/j.yexmp.2013.10.005, 24161954; Emuss, V., Garnett, M., Mason, C., Marais, R., Mutations of C-RAF are rare in human cancer because C-RAF has a low basal kinase activity compared with B-RAF (2005) Cancer Res, 65, pp. 9719-9726. , https://doi.org/10.1158/0008-5472.CAN-05-1683, 16266992; Wellbrock, C., Karasarides, M., Marais, R., The RAF proteins take centre stage (2004) Nat Rev Mol Cell Biol, 5, pp. 875-885. , https://doi.org/10.1038/nrm1498, 15520807; Dhomen, N., Marais, R., New insight into BRAF mutations in cancer (2007) Curr Opin Genet Dev, 17, pp. 31-39. , https://doi.org/10.1016/j.gde.2006.12.005, 17208430; Davies, H., Bignell, G.R., Cox, C., Mutations of the BRAF gene in human cancer (2002) Nature, 417, pp. 949-954. , https://doi.org/10.1038/nature00766, 12068308; Turbin, D.A., Cheang, M.C., Bajdik, C.D., Gelmon, K.A., Yorida, E., de Luca, A., Nielsen, T.O., Gilks, C.B., MDM2 protein expression is a negative prognostic marker in breast carcinoma (2006) Mod Pathol, 19 (1), pp. 69-74. , https://doi.org/10.1038/modpathol.3800484, 16258514; Bosmuller, H., Fischer, A., Pham, D.L., Fehm, T., Capper, D., von Deimling, A., Bonzheim, I., Fend, F., Detection of the B-RAF V600E mutation in serous ovarian tumors: A comparative analysis of immunohistochemistry with a mutation-specific monoclonal antibody and allele specific PCR (2013) Hum Pathol, 44, pp. 329-335. , https://doi.org/10.1016/j.humpath.2012.07.010, 23089489; Huss, S., Pasternack, H., Ihle, M.A., Merkelbach-Bruse, S., Heitktter, B., Hartmann, W., Trautmann, M., Wardelmann, E., Clinicopathological and molecular features of a large cohort of gastrointestinal stromal tumors (GISTs) and review of the literature: BRAF mutations in KIT/PDGFRA wild-type GISTs are rare events (2017) Hum Pathol, 62, pp. 206-214. , https://doi.org/10.1016/j.humpath.2017.01.005, 28159677; Busuttil, R.A., Zapparoli, G.V., Haupt, S., Fennell, C., Wong, S.Q., Pang, J.M., Takeno, E.A., Boussioutas, A., Role of p53 in the progression of gastric cancer (2014) Oncotarget, 5 (23), pp. 12016-12026. , https://doi.org/10.18632/oncotarget.2434, 25427447, PMC4322971; Cancer Incidence and Mortality Cancer Research United Kingdom, , http://info.cancerresearchuk.org, Accessed January, 2012; Gaballah, A., Moawad, M., Yassin, M., El-Wasly, N., El-Mahdy, M., Clinicopathological, epidemiological and outcome of treatment of advanced gastric cancer in Egypt: Single institution experience (2016) Annals of Oncology, 27 (2), pp. 86-101; Darwish, H., Sakr, A., Basaam, W., Ghorab, A., 10 years' Experience in the Treatment of Gastric Cancer: A Single Egyptian Cancer Center (NEMROCK) (2016) PAJO, 9 (3), pp. 35-41; Amieva, M., Peek, R.M., Jr., Pathobiology of Helicobacter pylori-induced gastric cancer (2015) Gastroenterology, 150, pp. 64-78. , https://doi.org/10.1053/j.gastro.2015.09.004, 26385073, PMC4691563; Hegazi, A., Hassan, E., El-Atrebi, K.A., El-Bassyouni, H.T., P53 protein and Ki-67 expression in chronic gastritis patients with positive Helicobacter pylori infection (2011) J Genetic Engin Biotechnol, 9 (1), pp. 73-76. , https://doi.org/10.1016/j.jgeb.2011.05.008; Sabry, D., Ahmed, R., Abdalla, S., Fathy, W., Eldemery, A., Braf, E.A., Kras and Helicobacter pylori epigenetic changes-associated chronic gastritis in Egyptian patients with and without gastric cancer (2016) World Journal of Microbiology and Biotechnology, 32 (6), p. 92. , https://doi.org/10.1007/s11274-016-2048-x, 27116958; Ramrez-Lzaro, M.J., Lario, S., Casalots, A., Sanfeliu, E., Boix, L., Garca-Iglesias, P., Snchez-Delgado, J., Calvet, X., Real-time PCR improves Helicobacter pylori detection in patients with peptic ulcer bleeding (2011) Plos One, 6 (5). , https://doi.org/10.1371/journal.pone.0020009, 21625499, PMC3098855; Wu, W.K., Cho, C.H., Lee, C.W., Fan, D., Wuk, Y.J., Sung, J.J., Dysregulation of cellular signaling in gastric cancer (2010) Cancer Lett, 295, pp. 144-153. , https://doi.org/10.1016/j.canlet.2010.04.025, 20488613; Wade, M., Li, Y.C., Wahl, G.M., MDM2, MDMX and p53 in oncogenesis and cancer therapy (2013) Nat Rev Cancer, 13, pp. 83-96. , https://doi.org/10.1038/nrc3430, 23303139, PMC4161369; Gunther, T., Schneider-Stock, R., Hackel, C., Kasper, H.U., Pross, M., Hackelsberger, A., Lippert, H., Roessner, A., Mdm2 gene amplification in gastric cancer correlation with expression of Mdm2 protein and p53 alterations (2000) Mod Pathol, 13, pp. 621-626. , https://doi.org/10.1038/modpathol.3880107, 10874665; Ye, Y., Li, X., Yang, J., Miao, S., Wang, S., Chen, Y., Xia, X., Zhou, J., MDM2 is a useful prognostic biomarker for resectable gastric cancer (2013) Cancer Sci, 104, pp. 590-598. , https://doi.org/10.1111/cas.12111, 23347235; Nakajima, N., Ito, Y., Yokoyama, K., Uno, A., Kinukawa, N., Nemoto, N., Moriyama, M., The Expression of Murine Double Minute 2 (MDM2) on Helicobacter pylori-Infected Intestinal Metaplasia and Gastric Cancer (2009) Journal of Clinical Biochemistry and Nutrition, 44, pp. 196-202. , https://doi.org/10.3164/jcbn.08-254, 19308274, PMC2654476; Shen, J., Niu, W., Zhou, M., Zhang, H., Ma, J., Wang, L., Zhang, H., MicroRNA-410 suppresses migration and invasion by targeting MDM2 in gastric cancer (2014) Plos One, 9 (8), p. 19; Hostein, I., Faur, N., Primois, C., Boury, F., Denard, J., Emile, F., Bringuier, P.P., Coindre, J.M., BRAF mutation status in gastrointestinal stromal tumors (2010) Am J Clin Pathol, 133 (1), pp. 141-148. , https://doi.org/10.1309/AJCPPCKGA2QGBJ1R, 20023270; Agaimy, A., Terracciano, L.M., Dirnhofer, S., Tornillo, L., Foerster, A., Hartmann, A., Bihl, M.P., V600E BRAF mutations are alternative early molecular events in a subset of KIT/PDGFRA wild-type gastrointestinal stromal tumours (2009) J Clin Pathol, 62 (7), pp. 613-616. , https://doi.org/10.1136/jcp.2009.064550, 19561230; Martinho, O., Gouveia, A., Viana-Pereira, M., Silva, P., Pimenta, A., Reis, R.M., Lopes, J.M., Low frequency of MAP kinase pathway alterations in KIT and PDGFRA wild-type GISTs (2009) Histopathology, 55 (1), pp. 53-62. , https://doi.org/10.1111/j.1365-2559.2009.03323.x, 19614767; Daniels, M., Lurkin, I., Pauli, R., Erbst��er, E., Hildebrandt, U., Hellwig, K., Zschille, U., Stengel, B., Spectrum of KIT/PDGFRA/BRAF mutations and Phosphatidylinositol-3-Kinase pathway gene alterations in gastrointestinal stromal tumors (GIST) (2011) Cancer Letters, 312 (1), pp. 43-54. , https://doi.org/10.1016/j.canlet.2011.07.029, 21906875; Lee, S.H., Lee, J.W., Soung, Y.H., Kim, H.S., Park, W.S., Kim, S.Y., Lee, J.H., Yoo, N.J., BRAF and KRAS mutations in stomach cancer (2003) Oncogene, 22 (44), pp. 6942-6945. , https://doi.org/10.1038/sj.onc.1206749, 14534542; Kim, T.M., Jung, S.H., Kim, M.S., Baek, I.P., Park, S.W., Lee, S.H., Lee, H.H., Lee, S.H., The mutational burdens and evolutionary ages of early gastric cancers are comparable to those of advanced gastric cancers (2014) J Pathol, 234, pp. 365-374. , https://doi.org/10.1002/path.4401, 25042771; Moradi, M.T., Salehi, Z., Asl, S.F., Aminian, K., Hashtchin, A.R., Helicobacter pylori infection and MDM2 SNP309 association with gastric cancer susceptibility (2013) Genetic Testing and Molecular Biomarkers, 17 (11), pp. 794-798. , https://doi.org/10.1089/gtmb.2013.0173, 24010568; Fenouille, N., Puissant, A., Tichet, M., Zimniak, G., Abbe, P., Mallavialle, A., Rocchi, S., Tartare-Deckert, S., SPARC functions as an anti-stress factor by inactivating p53 through Akt-mediated MDM2 phosphorylation to promote melanoma cell survival (2011) Oncogene, 30, pp. 4887-4900. , https://doi.org/10.1038/onc.2011.198, 21685937; Kodama, M., Fujioka, T., Murakami, K., Okimoto, T., Sato, R., Watanabe, K., Nasu, M., Eradication of Helicobacter pylori reduced the immunohistochemical detection of p53 and MDM2 in gastric mucosa (2005) J Gastroenterol Hepatol, 20, pp. 941-946. , https://doi.org/10.1111/j.1440-1746.2005.03880.x, 15946145; Sepideh, S., Mohammadreza, J.N., Ali, D., Holamreza, T.P., Samira, G., Study of the Murine Double Minute 2 status in patients with gastric and colorectal carcinomas and its correlation with prognostic factors (2012) Indian J Pathol Microbiol, 55, pp. 192-195. , https://doi.org/10.4103/0377-4929.97866, 22771642; Corso, G., Velho, S., Paredes, J., Pedrazzani, C., Martins, D., Milanezi, F., Pascale, V., Seruca, R., Oncogenic mutations in gastric cancer with microsatellite instability (2011) Eur J Cancer, 47, pp. 443-451. , https://doi.org/10.1016/j.ejca.2010.09.008, 20937558; Stella, G., Rojas Llimpe, F., Barone, C., Falcone, A., Di Fabio, F., Martoni, A., Lamba, S., Pinto, C., KRAS and BRAF mutational status as response biomarkers to cetuximab combination therapy in advanced gastric cancer patients (2009) Journal of Clinical Oncology, 27, p. e15503; Sasao, S., Hiyama, T., Tanaka, S., Yoshihara, M., Yasui, W., Chayama, K., Clinicopathologic and genetic characteristics of gastric cancer in young male and female patients (2006) Oncol Rep, 16, pp. 11-15. , https://doi.org/10.3892/or.16.1.11
dcterms.sourceScopus

Files

Original bundle

Now showing 1 - 2 of 2
Loading...
Thumbnail Image
Name:
avatar_scholar_256.png
Size:
6.31 KB
Format:
Portable Network Graphics
Description:
Loading...
Thumbnail Image
Name:
OAMJMS-6-1795.pdf
Size:
549.38 KB
Format:
Adobe Portable Document Format
Description: