Jump to ContentJump to Main Navigation
Show Summary Details
More options …


More options …
Volume 64, Issue 4


Expression of antiapoptotic protein survivin in malignant melanoma

Marian Adamkov
  • Institute of Histology and Embryology, Jessenius Faculty of Medicine, Comenius University, Malá Hora 4, SK-03601, Martin, Slovakia
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ L’udovít Lauko / Július Rajčáni / Soňa Bálentová
  • Institute of Histology and Embryology, Jessenius Faculty of Medicine, Comenius University, Malá Hora 4, SK-03601, Martin, Slovakia
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Silvia Rybárová
  • Department of Anatomy, Faculty of Medicine, P. J. Šafárik University, Šrobárova 2, SK-04180, Košice, Slovakia
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Dušan Mištuna
  • Clinic of Surgery, Jessenius Faculty of Medicine, Comenius University, MFN, Kollárova 2, SK-03601, Martin, Slovakia
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Dagmar Statelová
  • Clinic of Stomatology and Maxillofacial Surgery, Jessenius Faculty of Medicine, Comenius University, MFN, Kollárova 2, SK-03601, Martin, Slovakia
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2009-07-17 | DOI: https://doi.org/10.2478/s11756-009-0134-3


We examined the expression of potential tumor marker survivin by immunohistochemical staining using antisurvivin antibody (DAKO, Clone 12C4) in a panel of 25 malignant melanomas. In each section, we assessed the percentage of positively stained tumor cells, the intensity of staining and its subcellular localization. Survivin was present in 23 out of 25 cases (92%). Nuclear staining was found in 2 of these 23 cases (8.7%) only, while cytoplasmic staining only was seen in 3 of them (13%). The combined nuclear as well as cytoplasmic localization of survivin was demonstrated in 18 out of 23 cases (78.3%). In 2 cases revealing nuclear staining only, the worse histological features were more pronounced than in 3 cases with cytoplasmic staining only. Our results suggest that nuclear positivity of survivin may correlate with the degree of malignancy. In addition, we conclude that overexpression of survivin involved in the pathogenesis of melanoma represents an important diagnostic marker.

Keywords: melanoma; survivin; immunohistochemical staining; diagnostic marker

  • [1] Ackerman A.B. 1980. Malignant melanoma. A unifying concept. Am. J. Dermatopathol. 2: 309–313. http://dx.doi.org/10.1097/00000372-198000240-00004CrossrefGoogle Scholar

  • [2] Adamkov M., Lauko L., Balentova S., Pec J., Pec M. & Rajcani J. 2009. Expression pattern of antiapoptotic protein survivin in dysplastic nevi. Neoplasma 56: 130–135. http://dx.doi.org/10.4149/neo_2009_02_130CrossrefGoogle Scholar

  • [3] Alonso S.R., Ortiz P., Pollan M., Perez-Gomez B., Sanchez L., Acuna M.J., Pajares R., Martinez-Tello F.J., Hortelano C.M., Piris M.A. & Rodriguez-Peralto J.L. 2004. Progression in cutaneous malignant melanoma is associated with distinct expression profiles. Am. J. Pathol. 164: 193–203. Google Scholar

  • [4] Ambrosini G., Adida C. & Altieri D. 1997. A novel anti-apoptotic gene, survivin, expressed in cancer and lymphoma. Nat. Med. 3: 917–921. http://dx.doi.org/10.1038/nm0897-917CrossrefGoogle Scholar

  • [5] Amiri K.I. & Richmond A. 2005. Role of nuclear factor-k B in melanoma. Cancer Metastasis Rev. 24: 301–313. http://dx.doi.org/10.1007/s10555-005-1579-7CrossrefGoogle Scholar

  • [6] Armstrong B.K. & Kricker A. 2001. The epidemiology of UV induced skin cancer. J. Photochem. Photobiol. B63: 8–18. Google Scholar

  • [7] Breslow A. 1970. Thickness, cross-sectional areas and depth of invasion in the prognosis of cutaneous melanoma. Ann. Surg. 172: 902–908. http://dx.doi.org/10.1097/00000658-197011000-00017CrossrefGoogle Scholar

  • [8] Breslow A. 1979. Prognostic factors in the treatment of cutaneous melanoma. J. Cutan. Pathol. 6: 208–212. http://dx.doi.org/10.1111/j.1600-0560.1979.tb01125.xCrossrefGoogle Scholar

  • [9] Buttner P., Garbe C., Bertz J., Burg G., D’Hoedt B., Drepper H., Guggenmoos-Holzmann I., Lechner W., Lippold A., Orfanos C.E., Peters A., Rassner G., Stadler R. & Stroebel W. 1995. Primary cutaneous melanoma: optimized cutoff points of tumor thickness and importance of Clark’s level for prognostic classification. Cancer 75: 2499–2506. http://dx.doi.org/10.1002/1097-0142(19950515)75:10<2499::AID-CNCR2820751016>3.0.CO;2-8CrossrefGoogle Scholar

  • [10] Clark W.H. Jr, Elder D.E., Guerry D., Braitman L.E., Trock B.J., Schultz D., Synnestvedt M. & Halpern A.C. 1989. Model predicting survival in stage I melanoma based on tumor progression. J. Natl. Cancer Inst. 81: 1893–1904. http://dx.doi.org/10.1093/jnci/81.24.1893CrossrefGoogle Scholar

  • [11] Clark W.H. Jr, Elder D.E. & Van Horn M. 1986. The biologic forms of malignant melanoma. Hum. Pathol. 5: 443–450. http://dx.doi.org/10.1016/S0046-8177(86)80032-6CrossrefGoogle Scholar

  • [12] Deveraux Q.L. & Reed J.C. 1999. IAP family proteins-suppressors of apoptosis. Genes Dev. 13: 239–252. http://dx.doi.org/10.1101/gad.13.3.239CrossrefGoogle Scholar

  • [13] Deveraux Q.L., Takahashi R., Salvesen G.S. & Reed J.C. 1997. Xlinked IAP is a direct inhibitor of cell-death proteases. Nature 388: 300–304. http://dx.doi.org/10.1038/40901CrossrefGoogle Scholar

  • [14] Ding Y., Prieto V.G., Zhang P.S., Rosenthal S., Smith K.J., Skelton H.G. & Diwan A.H. 2006. Nuclear expression of the antiapoptoptic protein survivin in malignant melanoma. Cancer 106: 1123–1129. http://dx.doi.org/10.1002/cncr.21727CrossrefGoogle Scholar

  • [15] Dohi T., Beltrami E., Wall N.R., Plescia J. & Altieri D.C. 2004. Mitochondrial survivin inhibits apoptosis and promotes tumorigenesis. J. Clin. Invest. 114: 1117–1127. Google Scholar

  • [16] Eberle J., Fecker L.F., Forschner T., Ulrich C., Rowert-Huber J. & Stockfleth E. 2007. Apoptosis pathways as promosing targets for skin cancer therapy. Br. J. Dermatol. 156: 18–24. http://dx.doi.org/10.1111/j.1365-2133.2007.07855.xCrossrefGoogle Scholar

  • [17] Grossman D., McNiff J.M., Li F. & Altieri D.C. 1999. Expression and targeting of the apoptosis inhibitor, survivin, in human melamoma. J. Invest. Dermatol. 113: 1076–1081. http://dx.doi.org/10.1046/j.1523-1747.1999.00776.xCrossrefGoogle Scholar

  • [18] Jemal A., Siegel R., Ward E., Murray T., Xu J., Smigal C. & Thun M.J. 2006. Cancer statistics, 2006. CA Cancer J. Clin. 56: 106–130. http://dx.doi.org/10.3322/canjclin.56.2.106CrossrefGoogle Scholar

  • [19] Johnson M.E. & Howerth E.W. 2004. Survivin: a bifunctional inhibitor of apoptosis protein. Vet. Pathol. 41: 599–607. http://dx.doi.org/10.1354/vp.41-6-599CrossrefGoogle Scholar

  • [20] Jones P.A. 2001. Cancer: death and methylation. Nature 409: 143–144. http://dx.doi.org/10.1038/35051683CrossrefGoogle Scholar

  • [21] Li F. 2003. Survivin study: what is the next wave? J. Cell Physiol. 197: 8–29. http://dx.doi.org/10.1002/jcp.10327CrossrefGoogle Scholar

  • [22] Li F. 2005. Role of survivin and its splice variants in tumorigenesis. Br. J. Cancer. 92: 212–216. Google Scholar

  • [23] Li F. & Brattain M.G. 2006. Role of the survivin gene in pathobiology. Am. J. Pathol. 169: 1–11. http://dx.doi.org/10.2353/ajpath.2006.060121CrossrefGoogle Scholar

  • [24] Li F. & Ling X. 2006. Survivin study. An update of “What is the Next Wave?” Cell Physiol. 208: 476–486. http://dx.doi.org/10.1002/jcp.20634CrossrefGoogle Scholar

  • [25] Li F., Yang J., Rammath N., Javle M.M. & Tan D. 2005. Nuclear or cytoplasmic expression of survivin: what is significant? Int. J. Cancer. 114: 509–512. http://dx.doi.org/10.1002/ijc.20768CrossrefGoogle Scholar

  • [26] Liu, T., Biddle D., Hanks A.N., Brouha B., Yan H., Lee R.M., Leachman S.A. & Grossman D. 2006. Activation of dual apoptotic pathways in human melanocytes and protection by survivin. J. Invest. Dermatol. 126: 2247–2256. http://dx.doi.org/10.1038/sj.jid.5700381CrossrefGoogle Scholar

  • [27] Mesri M., Wall N.R., Li J., Kim R.W. & Altieri D.C. 2001. Cancer gene therapy using a survivin mutant adenovirus. J. Clin. Invest. 108: 981–990. Google Scholar

  • [28] Mihm M.C. Jr, Clark W.H. Jr. & From L. 1971. The clinical diagnosis, classification and histogenetic concepts of early stages of cutaneous malignant melanomas. N. Engl. J. Med. 284: 1078–1082. Google Scholar

  • [29] Nasr M.R. & El-Zammar O. 2008. Comparison of pHH3, Ki-67, and survivin immunoreactivity in benign and malignant melanocytic sesions. Am. J. Dermatol. 30: 117–122. http://dx.doi.org/10.1097/DAD.0b013e3181624054Google Scholar

  • [30] Piras F., Murtas D., Minerba L., Ugalde J., Floris C., Maxia C., Colombari R., Perra M.T. & Sirigu P. 2007. Nuclear survivin is associated with disease recurrence and poor survival in patients with cutaneous malignant melanoma. Histopathol. 50: 835–842. http://dx.doi.org/10.1111/j.1365-2559.2007.02695.xCrossrefGoogle Scholar

  • [31] Shin B.C., Sung B.J., Kim H., Kim H.J., Ha N.C., Hwang J.I., Chung C.W., Jung Y.K. & Oh B.H. 2001. An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and -7. Biochemistry 40: 1117–1123. http://dx.doi.org/10.1021/bi001603qCrossrefGoogle Scholar

  • [32] Sober A.J., Lew R.A., Koh H.K. & Bamhill R.L. 1991. Epidemiology of cutaneous melanoma: an update. Dermatol. Clin. 9: 617–629. Google Scholar

  • [33] Takeuchi H., Morton D.L., Elashoff D. & Hoon D.S. 2005. Survivin expression by metastatic melanoma predicts poor disease outcome in patients receiving adjuvant polyvalent vaccine. Int. J. Cancer. 117: 1032–1038. http://dx.doi.org/10.1002/ijc.21267CrossrefGoogle Scholar

  • [34] Tamm I., Kornblau S.M., Segall H., Krajewski S., Welsh K., Kitada S., Scudiero D.A., Tudor G., Qui Y.H., Monks A., Andreeff M. & Reed J.C. 2000. Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias. Clin. Cancer Res. 6: 1796–1803. Google Scholar

  • [35] Urist M.M. & Karnell L.H. 1994. The National Cancer Data Base: report on melanoma. Cancer 74: 782–788. http://dx.doi.org/10.1002/1097-0142(19940715)74:2<782::AID-CNCR2820740236>3.0.CO;2-GCrossrefGoogle Scholar

  • [36] Vucic D., Stennicke H.R., Pisabarro M.T., Salvesen G.S. & Dixit V.M. 2000. ML-IAP, a novel inhibitor of apoptosis that is preferentially expressed in human melanomas. Curr. Biol. 10: 1359–1366. http://dx.doi.org/10.1016/S0960-9822(00)00781-8CrossrefGoogle Scholar

  • [37] Xiao-Ming Y. & Zheng D. 2003. Essentials of Apoptosis. A Guide for Basic and Clinical Research. Humana Press, Inc., New Jersey, 259 pp. Google Scholar

  • [38] Zaffaroni N., Pennati M. & Daidone M.G. 2005. Survivin as a target for new anticancer interventions. J. Cell. Mol. Med. 9: 360–372. http://dx.doi.org/10.1111/j.1582-4934.2005.tb00361.xCrossrefGoogle Scholar

About the article

Published Online: 2009-07-17

Published in Print: 2009-08-01

Citation Information: Biologia, Volume 64, Issue 4, Pages 840–844, ISSN (Online) 1336-9563, ISSN (Print) 0006-3088, DOI: https://doi.org/10.2478/s11756-009-0134-3.

Export Citation

© 2009 Slovak Academy of Sciences. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. BY-NC-ND 3.0

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

Marian Adamkov, Martina Furjelová, Jaroslav Horáček, Marián Benčat, and Peter Kružliak
Acta Histochemica, 2014, Volume 116, Number 6, Page 1007
Marian Adamkov, Desanka Výbohová, Jaroslav Horáček, Mária Kovalská, and Martina Furjelová
Acta Histochemica, 2013, Volume 115, Number 5, Page 412

Comments (0)

Please log in or register to comment.
Log in