Expression of CMV protein pp65 in cutaneous malignant melanoma


Autoři: Margrét Agnarsdóttir aff001;  Svetlana Popova aff001;  Irina Alafuzoff aff001
Působiště autorů: Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden aff001;  Department of Clinical Pathology, Akademiska University Hospital, Uppsala, Sweden aff002
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0223854

Souhrn

Human cytomegalovirus (CVM) has been detected by immunohistochemistry (IHC) in brain tumours; however, whether CMV antigen is seen in melanomas has not yet been elucidated. Applying IHC, melanoma tissue was assessed for the expression of pp65, a tegument protein of CMV. Two cohorts were available, cohort-I and II, the latter included also related metastasis. In addition to IHC, in situ hybridisation (ISH) was carried out to assess whether CMV related genetic sequences were detectable in a subset of cases. Seventy per cent of the 142 cases in cohort-I and 50% of the 37 cases in cohort-II displayed immunoreactivity (IR). In both cohorts, the IHC outcome correlated with T-stage (Cohort I: Spearman 0.22, p = 0.01, Cohort II: Fisher exact text 0.04). In 30 of cohort-II cases, when IHC staining was carried out on both the primary tumour and the corresponding metastasis, no change in IR was noted in 53%; in 20%, the IR was lower and in 27% higher in the metastasis when compared with the primary tumour. These results were significant (Fisher exact test 0.03). Applying ISH technique on four tumour cases with detectable pp65 protein, CMV related genetic sequence was not detected. Here, we demonstrate, congruent with observations published for brain tumours, that the protein pp65 is indeed observed in substantial number of melanoma cases with IHC; however, no signal was detected with ISH technique. These findings are in line with previously reported studies, demonstrating that the role of CMV in tumours is still debatable.

Klíčová slova:

Antibodies – Human cytomegalovirus – Immunohistochemistry techniques – In situ hybridization – Malignant tumors – Melanomas – Metastasis – Skin tumors


Zdroje

1. Dziurzynski K, Chang SM, Heimberger AB, Kalejta RF, McGregor Dallas SR, Smit M, et al. Consensus on the role of human cytomegalovirus in glioblastoma. Neuro Oncol. 2012;14(3):246–55. doi: 10.1093/neuonc/nor227 22319219; PubMed Central PMCID: PMC3280809.

2. Gandhi MK, Khanna R. Human cytomegalovirus: clinical aspects, immune regulation, and emerging treatments. Lancet Infect Dis. 2004;4(12):725–38. doi: 10.1016/S1473-3099(04)01202-2 15567122.

3. Ludwig A, Hengel H. Epidemiological impact and disease burden of congenital cytomegalovirus infection in Europe. Euro Surveill. 2009;14(9):26–32. 19317969.

4. Mustakangas P, Sarna S, Ammala P, Muttilainen M, Koskela P, Koskiniemi M. Human cytomegalovirus seroprevalence in three socioeconomically different urban areas during the first trimester: a population-based cohort study. Int J Epidemiol. 2000;29(3):587–91. 10869335.

5. Green ML, Leisenring W, Xie H, Mast TC, Cui Y, Sandmaier BM, et al. Cytomegalovirus viral load and mortality after haemopoietic stem cell transplantation in the era of pre-emptive therapy: a retrospective cohort study. Lancet Haematol. 2016;3(3):e119–27. doi: 10.1016/S2352-3026(15)00289-6 26947200; PubMed Central PMCID: PMC4914379.

6. Feng S, Yang J, Wang W, Hu X, Liu H, Qian X, et al. Incidence and Risk Factors for Cytomegalovirus Infection in Patients With Kidney Transplantation: A Single-Center Experience. Transplant Proc. 2016;48(8):2695–9. doi: 10.1016/j.transproceed.2016.08.015 27788803.

7. Libard S, Popova SN, Amini RM, Karja V, Pietilainen T, Hamalainen KM, et al. Human cytomegalovirus tegument protein pp65 is detected in all intra- and extra-axial brain tumours independent of the tumour type or grade. PLoS One. 2014;9(9):e108861. doi: 10.1371/journal.pone.0108861 25268364; PubMed Central PMCID: PMC4182568.

8. Cobbs CS, Harkins L, Samanta M, Gillespie GY, Bharara S, King PH, et al. Human cytomegalovirus infection and expression in human malignant glioma. Cancer Res. 2002;62(12):3347–50. 12067971.

9. Baryawno N, Rahbar A, Wolmer-Solberg N, Taher C, Odeberg J, Darabi A, et al. Detection of human cytomegalovirus in medulloblastomas reveals a potential therapeutic target. J Clin Invest. 2011;121(10):4043–55. doi: 10.1172/JCI57147 21946257; PubMed Central PMCID: PMC3195466.

10. Scheurer ME, Bondy ML, Aldape KD, Albrecht T, El-Zein R. Detection of human cytomegalovirus in different histological types of gliomas. Acta Neuropathol. 2008;116(1):79–86. doi: 10.1007/s00401-008-0359-1 18351367; PubMed Central PMCID: PMC3001277.

11. Batich KA, Reap EA, Archer GE, Sanchez-Perez L, Nair SK, Schmittling RJ, et al. Long-term Survival in Glioblastoma with Cytomegalovirus pp65-Targeted Vaccination. Clin Cancer Res. 2017;23(8):1898–909. doi: 10.1158/1078-0432.CCR-16-2057 28411277; PubMed Central PMCID: PMC5559300.

12. Baumgarten P, Michaelis M, Rothweiler F, Starzetz T, Rabenau HF, Berger A, et al. Human cytomegalovirus infection in tumor cells of the nervous system is not detectable with standardized pathologico-virological diagnostics. Neuro Oncol. 2014;16(11):1469–77. doi: 10.1093/neuonc/nou167 25155358; PubMed Central PMCID: PMC4201076.

13. Holdhoff M, Guner G, Rodriguez FJ, Hicks JL, Zheng Q, Forman MS, et al. Absence of Cytomegalovirus in Glioblastoma and Other High-grade Gliomas by Real-time PCR, Immunohistochemistry, and In Situ Hybridization. Clin Cancer Res. 2017;23(12):3150–7. doi: 10.1158/1078-0432.CCR-16-1490 28034905; PubMed Central PMCID: PMC5474132.

14. Barukčić I. Human Cytomegalovirus is the cause of Glioblastoma Multiforme. Modern Health Science. 2018;1(2):19–36. https://doi.org/10.30560/mhs.v1n2p19.

15. Harkins L, Volk AL, Samanta M, Mikolaenko I, Britt WJ, Bland KI, et al. Specific localisation of human cytomegalovirus nucleic acids and proteins in human colorectal cancer. Lancet. 2002;360(9345):1557–63. doi: 10.1016/S0140-6736(02)11524-8 12443594.

16. Samanta M, Harkins L, Klemm K, Britt WJ, Cobbs CS. High prevalence of human cytomegalovirus in prostatic intraepithelial neoplasia and prostatic carcinoma. J Urol. 2003;170(3):998–1002. doi: 10.1097/01.ju.0000080263.46164.97 12913758.

17. Bai B, Wang X, Chen E, Zhu H. Human cytomegalovirus infection and colorectal cancer risk: a meta-analysis. Oncotarget. 2016;7(47):76735–42. doi: 10.18632/oncotarget.12523 27732934; PubMed Central PMCID: PMC5363545.

18. Zafiropoulos A, Tsentelierou E, Billiri K, Spandidos DA. Human herpes viruses in non-melanoma skin cancers. Cancer Lett. 2003;198(1):77–81. doi: 10.1016/s0304-3835(03)00269-6 12893433.

19. Landolfo S, Gariglio M, Gribaudo G, Lembo D. The human cytomegalovirus. Pharmacol Ther. 2003;98(3):269–97. doi: 10.1016/s0163-7258(03)00034-2 12782241.

20. Erdmann F, Lortet-Tieulent J, Schuz J, Zeeb H, Greinert R, Breitbart EW, et al. International trends in the incidence of malignant melanoma 1953-2008—are recent generations at higher or lower risk? Int J Cancer. 2013;132(2):385–400. doi: 10.1002/ijc.27616 22532371.

21. Balch CE, Gershenwald JE, Soong SJ, al e. Melanoma of the skin. In: Edge SE, Byrd DR, Carduccy MA, al e, editors. AJCC Cancer Staging Manual 7th ed. New York: Springer; 2009. p. 325–44.

22. Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Atkins MB, Byrd DR, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol. 2009;27(36):6199–206. doi: 10.1200/JCO.2009.23.4799 19917835; PubMed Central PMCID: PMC2793035.

23. Gershenwald JE, Scolyer RA, Hess KR, Sondak VK, Long GV, Ross MI, et al. Melanoma staging: Evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67(6):472–92. doi: 10.3322/caac.21409 29028110.

24. Morton DL, Thompson JF, Cochran AJ, Mozzillo N, Elashoff R, Essner R, et al. Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med. 2006;355(13):1307–17. doi: 10.1056/NEJMoa060992 17005948.

25. Faries MB, Thompson JF, Cochran AJ, Andtbacka RH, Mozzillo N, Zager JS, et al. Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma. N Engl J Med. 2017;376(23):2211–22. doi: 10.1056/NEJMoa1613210 28591523; PubMed Central PMCID: PMC5548388.

26. Eggermont AM, Spatz A, Robert C. Cutaneous melanoma. Lancet. 2014;383(9919):816–27. doi: 10.1016/S0140-6736(13)60802-8 24054424.

27. Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–23. doi: 10.1056/NEJMoa1003466 20525992; PubMed Central PMCID: PMC3549297.

28. Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364(26):2507–16. doi: 10.1056/NEJMoa1103782 21639808; PubMed Central PMCID: PMC3549296.

29. Agnarsdóttir M, Ponten F, Garmo H, Wagenius G, Mucci L, Magnusson K, et al. MITF Expression in Cutaneous Malignant Melanoma. J Mol Biomark Diagn 2012;3(4):129.

30. Kampf C, Olsson I, Ryberg U, Sjostedt E, Ponten F. Production of tissue microarrays, immunohistochemistry staining and digitalization within the human protein atlas. J Vis Exp. 2012;(63). Epub 2012/06/13. 3620 [pii]10.3791/3620. doi: 10.3791/3620 22688270; PubMed Central PMCID: PMC3468196.

31. Strickler JG, Manivel JC, Copenhaver CM, Kubic VL. Comparison of in situ hybridization and immunohistochemistry for detection of cytomegalovirus and herpes simplex virus. Hum Pathol. 1990;21(4):443–8. doi: 10.1016/0046-8177(90)90208-m 2156772.

32. Qureishi A, Mawby T, Fraser L, Shah KA, Moller H, Winter S. Current and future techniques for human papilloma virus (HPV) testing in oropharyngeal squamous cell carcinoma. Eur Arch Otorhinolaryngol. 2017;274(7):2675–83. doi: 10.1007/s00405-017-4503-1 28285422.

33. Martins LL, Rosseto JHF, Andrade NS, Franco JB, Braz-Silva PH, Ortega KL. Diagnosis of Oral Hairy Leukoplakia: The Importance of EBV In Situ Hybridization. Int J Dent. 2017;2017:3457479. doi: 10.1155/2017/3457479 28798771; PubMed Central PMCID: PMC5536144.


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PLOS One


2019 Číslo 10

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