Korelacija lokalne i sistemske ekspresije survivina sa patohistološkim parametrima melanoma kože

  • Milena Jović Institute for Pathology and Forensic Medicine, Military Medical Academy, Belgrade, Serbia
  • Snežana Cerović Institute for Pathology and Forensic Medicine, Military Medical Academy, Belgrade, Serbia; Faculty of Medicine of the Military Medical Academy, University of Defence, Belgrade, Serbia
  • Lidija Zolotarevska Institute for Pathology and Forensic Medicine, Military Medical Academy, Belgrade, Serbia; Faculty of Medicine of the Military Medical Academy, University of Defence, Belgrade, Serbia
  • Milomir Gačević Faculty of Medicine of the Military Medical Academy, University of Defence, Belgrade, Serbia; Clinic for Plastic Surgery and Burns, Military Medical Academy, Belgrade, Serbia
  • Ivan Stanojević Faculty of Medicine of the Military Medical Academy, University of Defence, Belgrade, Serbia; Institute for Medical Research, Military Medical Academy, Belgrade, Serbia
  • Karolina Miller Dorset County Hospital Foundation Trust, Dorchester, United Kingdom
  • Mirjana Djukić Department of Toxicology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
  • Luciano Saso Department of Physiology and Pharmacology, Sapienza University, Rome, Italy
  • Ljiljana Jauković Faculty of Medicine of the Military Medical Academy, University of Defence, Belgrade, Serbia; Institute for Nuclear Medicine, Military Medical Academy, Belgrade, Serbia
  • Danilo Vojvodić Faculty of Medicine of the Military Medical Academy, University of Defence, Belgrade, Serbia; Institute for Medical Research, Military Medical Academy, Belgrade, Serbia
DOI: https://doi.org/10.2298/VSP150519119J
Ključne reči: neoplasm proteins||, ||proteini, onkogeni, biological markers||, ||biološki pokazatelji, melanoma||, ||melanom, histology||, ||histologija, immunohistochemistry||, ||imunohistohemija, sensitivity and specificity||, ||osetljivost i specifičnost,

Sažetak


Uvod/Cilj. Survivin je multifunkcionalni protein bogato ispoljen u tumorima različite vrste, uključujući i melanom. Retki su radovi koji opisuju odnos ispoljavanja survivina u melanomskim ćelijama sa njegovom serumskom koncentracijom kao i sa histopatološkim karakteristikama melanoma. Cilj rada bio je da se ispita udruženost lokalne ekspresije survivina u tumoru (primarni tumor i metastatske promene) i serumske koncentracije sa kliničkim i histopatološkim parametrima kod bolesnika sa melanomom. Metode. Nivo ekspresije survivina određivan je imunocitohistohemijski u tumorskom tkivu i ELISA testom u serumu 84 bolesnika sa melanomom, dijagnostikovanih u periodu od 2009. do 2013. na Institutu za patologiju i sudsku medicinu i Institutu za medicinska istraživanja na Vojnomedicinskoj akademiji, Beograd, Srbija. Rezultati. Intezitet ekspresije survivina bio je značajno veći kod bolesnika čiji su tumori bili ulcerisani, sa visokim mitotskim indeksom, visokim Clark i Breslow indeksom, sa prisutnom vaskularnom i limfnom invazijom, kao i kod onih sa metastatskom bolesti. Ispoljavanje survivina i broj survivin pozitivnih ćelija u metastatskim lezijama bio je značajno udružen sa trajanjem intervala bez bolesti (disease free interval – DFI). Bolesnici sa visokim skorom ekspresije imali su skoro dvostruko kraći DFI u odnosu na one sa slabom lokalnom ekspresijom survivina i malim brojem survivin pozitivnih ćelija (9 ± 7 vs 19 ± 13 meseci). Stepen prisustva tumor infiltrišućih limfocita u tumorskom tkivu bio je značajno udružen sa koncetracijom survivina u serumu, sa najnižim prosečnim vrednostima detektovanim u uzorcima bolesnika sa najvećim stepenom infiltracije. Serumske koncentracije survivina bile su najveće u uzorcima bolesnika sa melanomom IA kliničkog stadijuma American Joint Commission on Cancer (AJCC), pT1a histološkog stadijuma, bolesnika čiji su tumori bili u horizontalnoj fazi rasta, bez znakova širenja limfohematogenim putem, sa najvećim brojem mitoza i koji su imali najmanji Clark indeks. Zaključak. Ekspresija survivina u tumorskom tkivu i njegova serumska koncentracija značajno korelišu sa kliničkim i histopatološkim parametrima melanoma. Serumski nivo može biti važan kao inicijalni indikator kod onih bolesnika koji bi mogli imati agresivan lokalni tumorski rast i širenje. Određivanje survivina u tumorskom tkivu, kako u primarnom tumoru tako i u metastazama, od velikog je značaja u utvrđivanju trajanja DFI.

Reference

McKenzie JA, Grossman D. Role of the apoptotic and mitotic regulator survivin in melanoma. Anticancer Res 2012; 32(2): 397−404.

Reed JC. The Survivin saga goes in vivo. J Clin Invest 2001; 108(7): 965−9.

Altieri DC. Survivin in apoptosis control and cell cycle regulation in cancer. Prog Cell Cycle Res 2003; 5: 447−52.

Dadras SS. Molecular diagnostics in melanoma: current status and perspectives. Arch Pathol Lab Med 2011; 135(7): 860−9.

Ding Y, Prieto VG, Zhang PS, Rosenthal S, Smith KJ, Skelton HG, et al. Nuclear expression of the antiapoptotic protein survivin in malignant melanoma. Cancer 2006; 106(5): 1123−9.

Vetter CS, Müller-Blech K, Schrama D, Bröcker E, Becker JC. Cytoplasmic and nuclear expression of survivin in melanocytic skin lesions. Arch Dermatol Res 2005; 297(1): 26−30.

Adamkov M, Lauko L, Balentova S, Pec J, Pec M, Rajcani J. Expression pattern of anti-apoptotic protein survivin in dysplastic nevi. Neoplasma 2009; 56(2): 130−35.

Tanaka K, Iwamoto S, Gon G, Nohara T, Iwamoto M, Tanigawa N. Expression of survivin and its relationship to loss of apoptosis in breast carcinoma. Cln Cancer Res 2000; 6: 127−34.

Altieri DC. Survivin, versatile modulation of cell division and apoptosis in cancer. Oncogene 2003; 22(53): 8581−9.

Srinivasula SM, Ashwell JD. IAPs: what's in a name. Mol Cell 2008; 30(2): 123−35.

Colnaghi R, Connell CM, Barrett RM, Wheatley SP. Separating the anti-apoptotic and mitotic roles of survivin. J Biol Chem 2006; 281(44): 33450−6.

Khan S, Jutzy JM, Aspe JR, McGregor DW, Neidigh JW, Wall NR. Survivin is released from cancer cells via exosomes. Apoptosis 2011; 16(1): 1−12.

Khan S, Bennit HF, Turay D, Perez M, Mirshahidi S, Yuan Y, et al. Early diagnostic value of survivin and its alternative splice variants in breast cancer. BMC Cancer 2014; 14: 176.

Raimondo S, Saieva L, Corrado C, Fontana S, Flugy A, Rizzo A, et al. Chronic myeloid leukemia-derived exosomes promote tumor growth through an autocrine mechanism. Cell Commun Signal 2015; 13: 8.

Grossman D, McNiff JM, Li F, Altieri DC. Expression and targeting of the apoptosis inhibitor, survivin, in human melanoma. J Invest Dermatol 1999; 113(6): 1076−81.

Thomas J, Liu T, Cotter MA, Florell SR, Robinette K, Hanks AN, et al. Melanocyte expression of survivin promotes development and metastasis of UV-induced melanoma in HGF-transgenic mice. Cancer Res 2007; 67(11): 5172−8.

McKenzie JA, Liu T, Goodson AG, Grossman D. Survivin enhances motility of melanoma cells bysupporting Akt activation and {alpha}5 integrin upregulation. Survivin enhances motility of melanoma cells bysupporting Akt activation and {alpha}5 integrin upregulation. Cancer Res 2010; 70(20): 7927−37.

Schramm SJ, Mann GJ. Melanoma prognosis: A REMARK-based systematic review and bioinformatic analysis of immunohistochemical and gene microarray studies. Mol Cancer Ther 2011; 10(8): 1520−8.

Piras F, Murtas D, Minerba L, Ugalde J, Floris C, Maxia C, et al. Nuclear survivin is associated with disease recurrence and poor survival in patients with cutaneous malignant melanoma. Histopathology 2007; 50(7): 835−42.

Takeuchi H, Morton DL, Elashoff D, Hoon DS. Survivin expression by metastatic melanoma predicts poor disease outcome in patients receiving adjuvant polyvalent vaccine. Int J Cancer 2005; 117(6): 1032−8.

Adamkov M, Lauko L, Rajčáni J, Bálentová S, Rybárová S, Mištuna D, et al. Expression of antiapoptotic protein survivin in malignant melanoma. Biologia 2009; 64(4): 840−4.

Takai N, Miyazaki T, Nishida M, Nasu K, Miyakawa I. Survivin expression correlates with clinical stage, histological grade, invasive behavior and survival rate in endometrial carcinoma. Cancer Lett 2002; 184(1): 105−16.

Cohen C, Lohmann CM, Cotsonis G, Lawson D, Santoianni R. Survivin expression in ovarian carcinoma: correlation with apoptotic markers and prognosis. Mod Pathol 2003; 16(6): 574−83.

Fields AC, Cotsonis G, Sexton D, Santoianni R, Cohen C. Survivin expression in hepatocellular carcinoma: correlation with proliferation, prognostic parameters, and outcome. Mod Pathol 2004; 17(11): 1378−85.

Nassar A, Lawson D, Cotsonis G, Cohen C. Survivin and caspase-3 expression in breast cancer: correlation with prognostic parameters, proliferation, angiogenesis, and outcome. Appl Immunohistochem Mol Morphol 2008; 16(2): 113−20.

Tsai W, Chu C, Yu C, Sheu L, Chen A, Chiang H, et al. Matriptase and survivin expression associated with tumor progression and malignant potential in breast cancer of Chinese women: tissue microarray analysis of immunostaining scores with clini-copathological parameters. Dis Markers 2008; 24(2): 89−99.

Qi Y, Li X, Li H, Zheng Y. The Research of Nanocrystallized Realgar for the Treatment of Skin Cancer. J Cancer Ther 2013; 4(6A): 43−7.

Reker S, Becker JC, Svane IM, Ralfkiaer E, Straten Pt, Andersen MH. HLA-B35-restricted immune responses against survivin in cancer patients. Int J Cancer 2004; 108(6): 937−41.

Andersen MH, Svane IM, Becker JC, Straten PT. The universal character of the tumor-associated antigen survivin. Clin Cancer Res 2007; 13(20): 5991−4.

Hadrup SR, Brændstrup O, Jacobsen GK, Mortensen S, Pedersen LØ, Seremet T, et al. Tumor infiltrating lymphocytes in seminoma lesions comprise clonally expanded cytotoxic T cells. Int J Cancer 2006; 119(4): 831−8.

Hadrup SR, Gehl J, Sørensen RB, Geertsen PF, Straten PT, Andersen MH. Persistence of survivin specific T cells for seven years in a melanoma patient during complete remission. Cancer Biol Ther 2006; 5(5): 480−2.

Ellebaek E, Iversen TZ, Junker N, Donia M, Engell-Noerregaard L, Met Ö, et al. Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose Interleukin-2 in metastatic melanom patients. J Transl Med 2012; 10: 169.

Junker N, Straten P, Andersen MH, Svane IM. Characterization of Ex Vivo Expanded Tumor Infiltrating Lymphocytes from Patients with Malignant Melanoma for Clinical Application. J Skin Cancer 2011; 6: 574695.

Junker N, Munir S, Kvistborg P, Straten Pt, Svane IM, Andersen MH. A Promiscuous Survivin-Derived T-Cell Epitope Restricted to the HLA-A3,er-Type Alleles. J Investig Dermatol 2012; 132(8): 2115−8.

McKenzie JA, Liu T, Jung JY, Jones BB, Ekiz HA, Welm AL, et al. Survivin promotion of melanoma metastasis requires upregulation of α5integrin. Carcinogenesis 2013; 34(9): 2137−44.

Tas F, Duranyildiz D, Argon A, Oguz H, Camlica H, Yasasever V, et al. Serum bcl-2 and survivin levels in melanoma. Melanoma Res 2004; 14(6): 543−6.

Goksel G, Taneli F, Uslu R, Ulman C, Dinc G, Coskun G, et al. Serum Her-2/neu and Survivin Levels and Their Relationship to Histological Parameters in Early-stage Breast. Cancer J Int Med Res 2007; 35(2): 165−72.

Objavljeno
2017/03/13
Broj časopisa
Vol. 73 Br. 11 (2016)
Rubrika
Originalni članak