Image Cytometric Analysis of P53 and Mdm-2 Expression in Primary and Recurrent Mucoepidermoid Carcinoma of Parotid Gland: Immunohistochemical Study

Overview

Journal Diagn Pathol

Publisher Biomed Central

Specialty Pathology

Date 2010 Nov 25

PMID 21092204

Citations 6

Authors

Ehab S Abd-Elhamid

Mohamed H Elmalahy

Affiliations

Soon will be listed here.

Abstract

Aims And Objectives: This study aims to analyze immunocytochemically p53 aberrant expression and mdm-2 expression in primary and recurrent mucoepidermoid carcinoma (MEC) of parotid gland and to ascertain if expression of these markers correlates with tumor behavior, clinical outcome, histological grade and local recurrence.

Methods: 20 cases histologically diagnosed as primary MEC with different grades were included in the study. Out of 20 cases, 7 were classified as grade I, 8 as grade II and 5 as grade III. Immunohistochemical staining of these 20 primary cases as well as 6 recurrent cases with anti-p53 and anti-mdm-2 antibodies was carried out. Area fraction of immunopositivity was estimated by image analysis software.

Results: 16/20 primary cases were p53 +ve (80%). The p53 positive cases included 3 cases classified as grade (I), 8 cases as grade (II) and 5 cases as grade (III). All 6 recurrent cases were p53 +ve. On the other hand, 14/20 primary and only 2/6 recurrent cases were mdm-2 +ve. The mdm-2 +ve primary cases included 2 classified as grade (I), 7 as grade (II) and 5 as grade (III). 12 primary MEC showed co-expression of both p53 and mdm-2 of which 2 cases showed local recurrence.

Conclusions: These data suggested that expression of p53 and mdm-2 in primary and recurrent MEC correlates with the high histological grade. P53 aberrant expression is not only considered as an early event in MEC carcinogenesis but also correlates to tumor behavior and local recurrence. Mdm-2 overexpression is correlated to pathogenesis of MEC. However, no strong evidence was found between mdm-2 expression and MEC local recurrence.

Citing Articles

The clinical outcome, pathologic spectrum, and genomic landscape for 454 cases of salivary mucoepidermoid carcinoma.

Wang X, Bai J, Yan J, Li B NPJ Precis Oncol. 2024; 8(1):238.

PMID: 39438706 PMC: 11496733. DOI: 10.1038/s41698-024-00735-2.

Odontogenic keratocyst: Analysis of recurrence by AgNOR, p53 and MDM2 profiling.

Chandrashekar C, Patel P, Thennavan A, Radhakrishnan R J Oral Maxillofac Pathol. 2020; 24(1):184-185.

PMID: 32508473 PMC: 7269273. DOI: 10.4103/jomfp.JOMFP_129_19.

p53 and Cell Fate: Sensitizing Head and Neck Cancer Stem Cells to Chemotherapy.

Rodriguez-Ramirez C, Nor J Crit Rev Oncog. 2018; 23(3-4):173-187.

PMID: 30311573 PMC: 6396309. DOI: 10.1615/CritRevOncog.2018027353.

Whole-Exome Sequencing of Salivary Gland Mucoepidermoid Carcinoma.

Kang H, Tan M, Bishop J, Jones S, Sausen M, Ha P Clin Cancer Res. 2016; 23(1):283-288.

PMID: 27340278 PMC: 5182193. DOI: 10.1158/1078-0432.CCR-16-0720.

Targeting MDM2 for Treatment of Adenoid Cystic Carcinoma.

Warner K, Nor F, Acasigua G, Martins M, Zhang Z, McLean S Clin Cancer Res. 2016; 22(14):3550-9.

PMID: 26936915 PMC: 4947417. DOI: 10.1158/1078-0432.CCR-15-1698.

References

Chen L, Agrawal S, Zhou W, Zhang R, Chen J . Synergistic activation of p53 by inhibition of MDM2 expression and DNA damage. Proc Natl Acad Sci U S A. 1998; 95(1):195-200. PMC: 18173. DOI: 10.1073/pnas.95.1.195. View

de Araujo V, Martins M, Leite K, Gomez R, de Araujo N . Immunohistochemical Mdm2 expression in minor salivary gland tumours and its relationship to p53 gene status. Oral Oncol. 2000; 36(1):67-9. DOI: 10.1016/s1368-8375(99)00054-8. View

Gallo O, Franchi A, Bianchi S, Boddi V, Giannelli E, ALAJMO E . p53 oncoprotein expression in parotid gland carcinoma is associated with clinical outcome. Cancer. 1995; 75(8):2037-44. DOI: 10.1002/1097-0142(19950415)75:8<2037::aid-cncr2820750802>3.0.co;2-v. View

Higashiyama M, Doi O, Kodama K, Yokouchi H, Kasugai T, Ishiguro S . MDM2 gene amplification and expression in non-small-cell lung cancer: immunohistochemical expression of its protein is a favourable prognostic marker in patients without p53 protein accumulation. Br J Cancer. 1997; 75(9):1302-8. PMC: 2228229. DOI: 10.1038/bjc.1997.221. View

Harris C, Hollstein M . Clinical implications of the p53 tumor-suppressor gene. N Engl J Med. 1993; 329(18):1318-27. DOI: 10.1056/NEJM199310283291807. View

Sheikh M, Shao Z, Hussain A, Fontana J . The p53-binding protein MDM2 gene is differentially expressed in human breast carcinoma. Cancer Res. 1993; 53(14):3226-8. View

Ohki K, Kumamoto H, Ichinohasama R, Suzuki M, Yamaguchi T, Echigo S . Genetic analysis of DNA microsatellite loci in salivary gland tumours: comparison with immunohistochemical detection of hMSH2 and p53 proteins. Int J Oral Maxillofac Surg. 2002; 30(6):538-44. DOI: 10.1054/ijom.2001.0161. View

Matizonkas-Antonio L, Mesquita R, de Souza S, Nunes F . TP53 mutations in salivary gland neoplasms. Braz Dent J. 2006; 16(2):162-6. DOI: 10.1590/s0103-64402005000200014. View

Brown D, Thomas C, Deb S . The human oncoprotein MDM2 arrests the cell cycle: elimination of its cell-cycle-inhibitory function induces tumorigenesis. EMBO J. 1998; 17(9):2513-25. PMC: 1170593. DOI: 10.1093/emboj/17.9.2513. View

10.

Giordana M, Duo D, Gasverde S, Trevisan E, Boghi A, Morra I . MDM2 overexpression is associated with short survival in adults with medulloblastoma. Neuro Oncol. 2002; 4(2):115-22. PMC: 1920659. DOI: 10.1093/neuonc/4.2.115. View

11.

Nordkvist A, Roijer E, Bang G, Gustafsson H, Behrendt M, Ryd W . Expression and mutation patterns of p53 in benign and malignant salivary gland tumors. Int J Oncol. 2000; 16(3):477-83. DOI: 10.3892/ijo.16.3.477. View

12.

Sompuram S, Kodela V, Zhang K, Ramanathan H, Radcliffe G, Falb P . A novel quality control slide for quantitative immunohistochemistry testing. J Histochem Cytochem. 2002; 50(11):1425-34. DOI: 10.1177/002215540205001101. View

13.

Haitel A, Wiener H, Baethge U, Marberger M, Susani M . mdm2 expression as a prognostic indicator in clear cell renal cell carcinoma: comparison with p53 overexpression and clinicopathological parameters. Clin Cancer Res. 2000; 6(5):1840-4. View

14.

Prives C, Hall P . The p53 pathway. J Pathol. 1999; 187(1):112-26. DOI: 10.1002/(SICI)1096-9896(199901)187:1<112::AID-PATH250>3.0.CO;2-3. View

15.

Agarwal M, Taylor W, Chernov M, Chernova O, Stark G . The p53 network. J Biol Chem. 1998; 273(1):1-4. DOI: 10.1074/jbc.273.1.1. View

16.

Okeefe K, Li H, Zhang Y . Nucleocytoplasmic shuttling of p53 is essential for MDM2-mediated cytoplasmic degradation but not ubiquitination. Mol Cell Biol. 2003; 23(18):6396-405. PMC: 193719. DOI: 10.1128/MCB.23.18.6396-6405.2003. View

17.

Vogelstein B, Lane D, Levine A . Surfing the p53 network. Nature. 2000; 408(6810):307-10. DOI: 10.1038/35042675. View

18.

Claudio P, Zamparelli A, Garcia F, Claudio L, Ammirati G, Farina A . Expression of cell-cycle-regulated proteins pRb2/p130, p107, p27(kip1), p53, mdm-2, and Ki-67 (MIB-1) in prostatic gland adenocarcinoma. Clin Cancer Res. 2002; 8(6):1808-15. View

19.

Karja V, Syrjanen K, Kurvinen A, Syrjanen S . Expression and mutations of p53 in salivary gland tumours. J Oral Pathol Med. 1997; 26(5):217-23. DOI: 10.1111/j.1600-0714.1997.tb01227.x. View

20.

Zhang Z, Li M, Wang H, Agrawal S, Zhang R . Antisense therapy targeting MDM2 oncogene in prostate cancer: Effects on proliferation, apoptosis, multiple gene expression, and chemotherapy. Proc Natl Acad Sci U S A. 2003; 100(20):11636-41. PMC: 208810. DOI: 10.1073/pnas.1934692100. View