Evaluation of Cyclooxygenase-2 Expression in Association with Clinical-Pathological Factors in Malignant Melanoma

Document Type: Original Research

Authors

1 Associate Professor of Pathology, Department Of Pathology, Cancer Molecular Pathology Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Assistant Professor of Pathology, Department Of Pathology, Cancer Molecular Pathology Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

3 Cancer Molecular Pathology Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

10.30699/ijp.14.2.96

Abstract

Background and Objective: The primary goal of this study is to develop a rigorous understanding ofthe correlation between COX-2 expression and malignant melanoma prognostic factors.
Material and Methods: In this cross-sectional study, we analyzed 60 cases of cutaneous malignant melanoma. The related stained slides were reviewed by two pathologists. The results were interpreted according to the COX2 staining index (SI), tumor thickness (Breslow, Clark), number of mitoses per 10 hpf, and melanoma types. Gender, lymph node involvement, metastasis, and survival were considered as evaluation factors as well.
 Results: The expression of the COX-2 protein was evident in 98.4% of cases. A strong Staining Index(SI) was reported in 60% of all melanomas, moderate staining was detected in 20.8% and weak staining in 10%; 1.6% of studied cases showed no staining. Benign nevus specimens showed no staining for the COX-2 enzyme.
Conclusion: We have demonstrated that COX-2 is strongly expressed in the majority of malignant melanomas and that the SI score of COX-2 is related to the number of mitoses, tumor thickness (based on Clark level and Breslow), melanoma sub-type, lymph node involvement, and metastases; No association was noted between the anatomic site, gender, and survival. COX-2 can be applied as a prognostic factor in malignant melanoma and a promising candidate for future target therapies.

Keywords

Main Subjects


  1. Jemal A, Saraiya M, Patel P, Cherala SS, Barnholtz-Sloan J, Kim J, Wiggins CL, Wingo PA. Recent trends in cutaneous melanoma incidence and death rates in the United States, 1992-2006. Journal of the American Academy of Dermatology. 2011 Nov 1; 65(5):S17-e1.
    https://doi.org/10.1016/j.jaad.2011.04.032
  2. Hicks MJ, Flaitz CM. Oral mucosal melanoma: epidemiology and pathobiology. Oral oncology. 2000 Mar 1; 36(2):152-69.            
    https://doi.org/10.1016/S1368-8375(99)00085-8
  3. Lens MB, Dawes M. Global perspectives of contemporary epidemiological trends of cutaneous malignant melanoma. British Journal of Dermatology. 2004 Feb; 150(2):179-85.      
    https://doi.org/10.1111/j.1365-2133.2004.05708.x
  4. Rahnama Z, Meymandi SS, Nasiri N. Cutaneous melanoma in a desert climate zone: a retrospective study of 125 cases. International journal of dermatology. 2010 Apr;49(4):406-9.https://doi.org/10.1111/j.1365-4632.2010.04290.
  5. Kim KM, Im AR, Kim SH, Hyun JW, Chae S. Timosaponin AIII inhibits melanoma cell migration by suppressing COX‐2 and in vivo tumor metastasis. Cancer science. 2016 Feb; 107(2):181-8.             
    https://doi.org/10.1111/cas.12852
  6. Hocker TL, Singh MK, Tsao H. Melanoma genetics and therapeutic approaches in the 21st century: moving from the benchside to the bedside. J Invest Dermatol. 2008 Nov; 128(11):2575-95.      
    https://doi.org/10.1038/jid.2008.226
  7. Cummins DL, Cummins JM, Pantle H, Silverman MA, Leonard AL, Chanmugam A. Cutaneous malignant melanoma. Mayo Clin Proc. 2006 Apr; 81(4):500-7.
    https://doi.org/10.4065/81.4.500
  8. Guitart J, Lowe L, Piepkorn M, Prieto VG, Rabkin MS, Ronan SG, et al. Histological characteristics of metastasizing thin melanomas: a case-control study of 43 cases. Arch Dermatol. 2002 May; 138(5):603-8.    
    https://doi.org/10.1001/archderm.138.5.603
  9. Prieto VG, Shea CR. Use of immunohistochemistry in melanocytic lesions. Journal of cutaneous pathology. 2008 Nov;35:1-10.      
    https://doi.org/10.1111/j.1600-0560.2008.01130.x
  10. Salmon PJ, Chan WC, Griffin J, McKenzie R, Rademaker M. Extremely high levels of melanoma in Tauranga, New Zealand: possible causes and comparisons with Australia and the northern hemisphere. Australas J Dermatol. 2007 Nov; 48(4):208-16.         
    https://doi.org/10.1111/j.1440-0960.2007.00388.x
  11. Kowalzic L, Eickenscheidt L, Seidel C, Kribus S, Ziegler H, Komar M. Telangiectasia macularis eruptiva perstans, a form of cutaneous mastocytosis, associated with malignant melanoma. JDDG: J Dtsch Dermatol Ges. 2009 Apr; 7(4):360-2.               
    https://doi.org/10.1111/j.1610-0387.2008.06941.x
  12. Ambretti S, Venturoli S, Mirasoli M, La Placa M, Bonvicini F, Cricca M et al. Assessment of the presence of mucosal human papillomaviruses in malignant melanomas using combined fluorescent in situ hybridization and chemiluminescent immunohistochemistry. Br J Dermatol. 2007 Jan; 156(1): 38-44. https://doi.org/10.1111/j.1365-2133.2006.07541 .x
  13. Paradisi A, Capizzi R, De Simone C, Fossati B, Proietti I, Amerio PL. Malignant melanoma in a tattoo: case report and review of the literature. Melanoma Res. 2006 Aug;16(4):375-6.
  14. Attis MG, Vollmer RT. Mitotic rate in melanoma, a recomination. Am J Clin Pathol. 2007 Mar; 127(3):380-4. https://doi.org/10.1309/LB7RTC61B7LC6HJ6
  15. Noorbala MT, Mohammadi S, Noorbala M.Cutaneous malignant melanoma in central Iran: a 20-year study. Iran Red Crescent Med J. 2013 Aug;15(8):690-4.
    https://doi.org/10.5812/ircmj.5364
  16. Meeran SM, Punathil T, Katiyar SK. IL-12 deficiency exacerbates inflammatory responses in UV-irradiated skin and skin tumors. J Invest Dermatol. 2008 Nov;128(11):2716-27.
    https://doi.org/10.1038/jid.2008.140
  17. Sharma SD, Katiyar SK. Dietary grape seed proanthocyanidins inhibit UVB-induced cyclooxygenase-2 expression and other inflammatory mediators in UVB-exposed skin and skin tumors of SKH-1 hairless mice. Pharm Res. 2010 Jun;27(6):1092-102.
    https://doi.org/10.1007/s11095-010-0050-9
  18. Denkert C, Köbel M, Berger S, Siegert A, Leclere A, Trefzer U, et al. Expression of cyclooxygenase 2 in human malignant melanoma. Cancer Res. 2001 Jan 1;61(1):303-8.
  19. Dannenberg AJ, Altorki NK, Boyle JO, Lin DT, Subbaramaiah K. Inhibition of cyclooxygenase-2: an approach to preventing cancer of the upper aerodigestive tract. Ann N Y Acad Sci. 2001 Dec; 952:109-15.            
    https://doi.org/10.1111/j.17496632.2001.tb02731.x
  20. Kogushi-Nishi H, Kawasaki J, Kageshita T, Ishihara T, Ihn H. The prevalence of melanocytic nevi on the soles in the Japanese population. J Am Acad Dermatol. 2009 May;60(5):767-71.
    https://doi.org/10.1016/j.jaad.2008.12.048
  21. Rao BK, Noor O, Thosani MK. Identical twins with primary cutaneous melanoma presenting at the same time and location. Am J Dermatopathol. 2008 Apr;30(2):182-4.
    https://doi.org/10.1097/DAD.0b013e318164fc87
  22. Handerson T, Berger A, Harigopol M, Rimm D, Nishigori C, Ueda M, et al. Melanophages reside in hypermelanotic, aberrantly glycosylated tumor areas and predict improved outcome in primary cutaneous malignant melanoma. J Cutan Pathol. 2007 Sep;34 (9):679-86.
    https://doi.org/10.1111/j.1600-0560.2006.00681.x
  23. Becker MR, Siegelin MD, Rompel R, Enk AH, Gaiser T. COX-2 expression in malignant melanoma: a novel prognostic marker?. Melanoma research. 2009 Feb 1;19(1):8-16. https://doi.org/10.1097/CMR.0b013e32831d7f52
  24. Becker MR, Siegelin MD, Rompel R, Enk AH, Gaiser T. Peroxisome proliferator‐activated receptors in squamous cell carcinoma and its precursors. J Melanoma Res. 2009 Feb;19(1):8-16.
    https://doi.org/10.1097/CMR.0b013e32831d7f52
  25. Cruess SR, Caissie AL, Correia CP, Callejo SA, Burnier MN. Correlation of Cyclooxygenase-2 (COX-2) Expression and Interconverted Phenotype in Uveal Melanoma. Investigative Ophthalmology & Visual Science. 2002 Dec 1;43(13):1143