Advertisement

European Journal of Dermatology

, Volume 27, Issue 6, pp 627–634 | Cite as

Comparative study of the clinical, histological, and biological characteristics of squamous cell carcinomas in areas previously treated with photodynamic therapy

  • Tamara Gracia CazañaEmail author
  • Nerea Salazar
  • Jesús Vera-Álvarez
  • Salvador González
  • Angeles Juarranz
  • Yolanda Gilaberte
Clinical report
  • 30 Downloads

Abstract

Background

Although photodynamic therapy (PDT) is an effective treatment option for non-melanoma skin cancer, the development of aggressive tumours in PDT-treated areas has been described.

Objectives

To evaluate the clinical, histological, and biological characteristics of squamous cell carcinomas (SCCs) in areas previously treated with PDT vs those arising in areas never treated with this therapeutic modality.

Materials & methods

Aretrospective observational studywas designed. We collected all cases of invasive SCCs in areas previously treated with PDT. The control group consisted of an equivalent number of SCCs randomly selected from the database of our pathology department. Expression of specific markers implicated in SCC progression, including p53, Ki67, COX-2, cyclin D1, E-cadherin, EGFR, survivin, and pERK, was analysed.

Results

A total of 699 patients were treated with PDT for non-melanoma skin cancer during the course of the study. Ten invasive SCCs arising in areas previously treated with methylaminolevulinate-PDT were diagnosed in six patients. The control group consisted of 10 invasive SCCs from 10 patients never treated with PDT. In the PDT group, the mean tumour size was significantly lower and the absence of ulceration was more frequent than in the control group (p<0.024 and p = 0.035, respectively). Adiffuse survivin staining pattern was observed in 90% of tumours in the PDT group versus 50% in the comparative group (p = 0.141).

Conclusion

The number of SCCs arising in areas previously treated with PDT was very low and did not differ significantly from that of SCCs developing in non-PDT-treated areas.

Key words

photodynamic therapy non-melanoma skin cancer squamous cell carcinomas p53 Ki67 COX-2 cyclin D1 E-cadherin EGFR survivin pERK 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Szeimies RM, Morton CA, Sidoroff A, et al. Photodynamic therapy for nonmelanoma skin cancer. Acta Derm Venereol 2005; 85: 483–90.PubMedGoogle Scholar
  2. 2.
    Freeman M, Vinciullo C, Francis D, et al. A comparison of photodynamic therapy using topical methyl aminolevulinate (Metvix) with single cycle cryotherapy in patients with actinic keratosis: a prospective, randomized study. J Dermatolog Treat 2003; 14: 99–106.CrossRefGoogle Scholar
  3. 3.
    Lucena SR, Salazar N, Gracia-Caza˜na T, et al. Combined treatments with photodynamic therapy for non-melanoma skin cancer. Int J Mol Sci 2015; 16: 25912–33.CrossRefGoogle Scholar
  4. 4.
    Takahashi H, Nakajima S, Sakata I. ATX-S10(Na)-photodynamic therapy is less carcinogenic for mouse skin compared with ultraviolet B irradiation. Br J Dermatol 2005; 153: 1182–6.CrossRefGoogle Scholar
  5. 5.
    Fuchs J, Weber S, Kaufmann R. Genotoxic potential of porphyrin type photosensitizers with particular emphasis on 5-aminolevulinic acid: implications for clinical photodynamic therapy. Free Radic Biol Med 2000; 28: 537–48.CrossRefGoogle Scholar
  6. 6.
    Ratour-Bigot C, Chemidling M, Montlahuc C, et al. Squamous cell carcinoma following photodynamic therapy for cutaneous Bowen’s disease in a series of 105 patients. Acta Derm Venereol 2016; 96: 658–63.CrossRefGoogle Scholar
  7. 7.
    Maydan E, Nootheti PK, Goldman MP. Development of a keratoacanthoma after topical photodynamic therapy with 5-aminolevulinic acid. J Drugs Dermatol 2006; 5: 804–6.PubMedGoogle Scholar
  8. 8.
    Schreml S, Gantner S, Steinbauer J, et al. Melanoma promotion after photodynamic therapy of a suspected Bowen’s disease lesion. Dermatology 2009; 219: 279–81.CrossRefGoogle Scholar
  9. 9.
    Karen JK, Hale EK. Rapid progression of a basal cell carcinoma after photodynamic therapy. Dermatol Surg 2010; 36: 1328–31.CrossRefGoogle Scholar
  10. 10.
    Liang WM, Theng TS, Lim KS, et al. Rapid development of squamous cell carcinoma after photodynamic therapy. Dermatol Surg 2014; 40: 586–8.CrossRefGoogle Scholar
  11. 11.
    Gilaberte Y, Milla L, Salazar N, et al. Cellular intrinsic factors involved in the resistance of squamous cell carcinoma to photodynamic therapy. J Invest Dermatol 2014; 134: 2428–37.CrossRefGoogle Scholar
  12. 12.
    Bardazzi F, Loi C, Magnano M, et al. Methyl-aminolevulinic acid photodynamic therapy for actinic keratoses: a useful treatment or a risk factor? A retrospective study. J Dermatolog Treat 2015; 26: 168–70.CrossRefGoogle Scholar
  13. 13.
    Attili Sk, Ibbotson SH, Fleming C. Role of a non-surgical therapies in the management of periocular basal cell carcinoma and squamous intra-epidermal carcinoma: a case series and review of the literature. Photodermatol Photoimmunol Photomed 2012; 28: 68–79.CrossRefGoogle Scholar
  14. 14.
    Ruini C, Witkowski AM, Cesinaro A, et al. From actinic keratosis to squamous cell carcinoma: evidence of morphologic and biologic progression. J Am Acad Dermatol 2015; 72: S8–10.CrossRefGoogle Scholar
  15. 15.
    Fernández-Figueras MT, Carrato C, et al. Actinic keratosis with atypical basal cells (AK I) is the most common lesion associated with invasive squamous cell carcinoma of the skin. J Eur Acad Dermatol Venereol 2015; 29: 991–7.CrossRefGoogle Scholar
  16. 16.
    LeBoit PE, Burg G, Weedon D. Pathology and genetics of skin tumors. World Health Organization Classification of Tumours. Lyon: IARC Press, 2006.Google Scholar
  17. 17.
    Bagazgoitia L, Cuevas Santos J, Juarranz A, et al. Photodynamic therapy reduces the histological features of actinic damage and the expression of early oncogenic markers. Br J Dermatol 2011; 165: 144–51.CrossRefGoogle Scholar
  18. 18.
    Milla LN, Cogno IS, Rodríguez ME, et al. Isolation and characterization of squamous carcinoma cells resistant to photodynamic therapy. J Cell Biochem 2011; 112: 2266–78.CrossRefGoogle Scholar
  19. 19.
    Kick G, Messer G, Lewig G, et al. Strong and prolonged induction of c-jun and c-fos proto-oncogenes by photodynamic therapy. Br J Cancer 1996; 74: 30–6.CrossRefGoogle Scholar
  20. 20.
    Thanos SM, Halliday GM, Damian DL. Nicotinamide reduces photodynamic therapy-induced immunosuppression in humans. Br J Dermatol 2012; 167: 631–6.CrossRefGoogle Scholar
  21. 21.
    Calista D. Development of squamous cell carcinoma after photodynamic therapy with methyl aminoleuvulinate. Br J Dermatol 2014; 171: 905–8.CrossRefGoogle Scholar
  22. 22.
    Varma S, Holt PJ, Anstey AV. Erythroplasia of Queyrat treated by topical aminolaevulinic acid photodynamic therapy: a cautionary tale. Br J Dermatol 2000; 142: 825–6.CrossRefGoogle Scholar
  23. 23.
    Casas A, Di Venosa G, Hasan T, et al. Mechanisms of resistance to photodynamic therapy. Curr Med Chem 2011; 18: 2486–515.CrossRefGoogle Scholar
  24. 24.
    Muthusamy V, Piva TJ. The UV response of the skin: a review of the MAPK, NF-κB and TNF-α signal transduction pathways. Arch Dermatol Res 2010; 302: 5–17.CrossRefGoogle Scholar
  25. 25.
    Evangelou G, Farrar MD, Cotterell L, et al. Topical photodynamic therapy significantly reduces epidermal Langerhans cells during clinical treatment of basal cell carcinoma. Br J Dermatol 2012; 166: 1112–5.CrossRefGoogle Scholar
  26. 26.
    Luna MC, Gomer CJ. Isolation and initial characterization of mouse tumor cells resistant to porphyrin-mediated photodynamic therapy. Cancer Res 1991; 51: 4243–9.PubMedGoogle Scholar
  27. 27.
    Rebucci M, Michiels C. Molecular aspects of cancer cell resistance to chemotherapy. Biochem Pharmacol 2013; 85: 1219–26.CrossRefGoogle Scholar
  28. 28.
    Trindade GS, Farias SL, Rumjanek VM, et al. Methylene blue reverts multidrug resistance: sensitivity of multidrug resistant cells to this dye and its photodynamic action. Cancer Lett 2000; 151: 161–7.CrossRefGoogle Scholar
  29. 29.
    Tsai T, Hong RL, Tsai JC, et al. Effect of 5-aminolevulinic acidmediated photodynamic therapy on MCF-7 and MCF-7/ADR cells. Lasers Surg Med 2004; 34: 62–72.CrossRefGoogle Scholar
  30. 30.
    Weyergang A, Berstad ME, Bull-Hansen B, et al. Photochemical activation of drugs for the treatment of therapy-resistant cancers. Photochem Photobiol Sci 2015; 14: 1465–75.CrossRefGoogle Scholar
  31. 31.
    Hoffman WH, Biade S, Zilfou JT, et al. Transcriptional repression of the antiapoptotic survivin gene by wild type p53. J Biol Chem 2002; 277: 3247–57.CrossRefGoogle Scholar
  32. 32.
    Roy P, Nigam N, George J, et al. Induction of apoptosis by tea polyphenols mediated through mitochondrial cell death pathway in mouse skin tumors. Cancer Biol Ther 2009; 8: 1281–7.CrossRefGoogle Scholar
  33. 33.
    Dallaglio K, Marconi A, Pincelli C. Survivin: a dual player in healthy and diseased skin. J Invest Dermatol 2012; 132: 18–27.CrossRefGoogle Scholar
  34. 34.
    Lotti R, Palazzo E, Petrachi T, et al. Survivin modulates squamous cell carcinoma-derived stem-like cell proliferation, viability and tumor formation in vivo. Int J Mol Sci 2016; 17: e89.CrossRefGoogle Scholar

Copyright information

© JLE/Springer 2018

Authors and Affiliations

  • Tamara Gracia Cazaña
    • 1
    Email author
  • Nerea Salazar
    • 2
  • Jesús Vera-Álvarez
    • 3
  • Salvador González
    • 4
  • Angeles Juarranz
    • 2
  • Yolanda Gilaberte
    • 5
  1. 1.Dermatology ServiceHospital de BarbastroHuescaSpain
  2. 2.Biology DepartmentUniversidad Autónoma de MadridMadridSpain
  3. 3.Pathology ServiceHospital San JorgeHuescaSpain
  4. 4.Dermatology ServiceMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  5. 5.Dermatology ServiceHospital San JorgeHuescaSpain

Personalised recommendations