Correlation of local and systemic expression of survivin with histopathological parameters of cutaneous melanoma

Jović, Milena; Cerović, Snežana; Zolotarevska, Lidija; Gačević, Milomir; Stanojević, Ivan; Miller, Karolina; Đukić, Mirjana; Saso, Luciano; Jauković, Ljiljana; Vojvodić, Danilo

doi:10.2298/VSP150519119J

Akcije

dodaj u Moj izbor [0]

kako citirati ovaj članak
prikaži na oba jezika
podeli ovaj članak

Direktan link

Metrika

citati u SCIndeksu: 0
citati u CrossRef-u:0
citati u Google Scholaru:[]
posete u poslednjih 30 dana:1
preuzimanja u poslednjih 30 dana:1

Sadržaj

članak: 8 od 53

povratak na rezultate

Vojnosanitetski pregled

2016, vol. 73, br. 11, str. 1022-1029

Korelacija lokalne i sistemske ekspresije survivina sa patohistološkim parametrima melanoma kože

Jović Milena^a, Cerović Snežana^b, Zolotarevska Lidija^b, Gačević Milomir^c, Stanojević Ivan^d, Miller Karolina^e, Đukić Mirjana^f

, Saso Luciano^g, Jauković Ljiljana^h, Vojvodić Danilo^d

^aVojnomedicinska akademija, Institut za patologiju i sudsku medicinu, Beograd
^bVojnomedicinska akademija, Institut za patologiju i sudsku medicinu, Beograd + Univerzitet odbrane, Medicinski fakultet Vojnomedicinske akademije, Beograd
^cUniverzitet odbrane, Medicinski fakultet Vojnomedicinske akademije, Beograd + Vojnomedicinska akademija, Klinika za plastičnu hirurgiju i opekotine, Beograd
^dUniverzitet odbrane, Medicinski fakultet Vojnomedicinske akademije, Beograd + Vojnomedicinska akademija, Institut za medicinska istraživanja, Beograd
^eDorset County Hospital Foundation Trust, Dorchester, United Kingdom
^fUniverzitet u Beogradu, Farmaceutski fakultet, Institut za toksikološku hemiju
^gDepartment of Physiology and Pharmacology, Sapienza University, Rome, Italy
^hUniverzitet odbrane, Medicinski fakultet Vojnomedicinske akademije, Beograd + Vojnomedicinska akademija, Institut za naučne informacije, Beograd

e-adresa: alhemastro@gmail.com

Ključne reči: proteini; onkogeni; biološki pokazatelji; melanom; histologija; imunohistohemija; 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 utumorskom tkivu i ELISA testom u serumu 84 bolesnika sa melanomom, dijagnostikovanih u periodu od 2009. do 2013. na Institutu za patologiju i sudsku medicínu 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 infltrišućih 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.

Abstract

Background/Aim. Survivin is a multifunctional protein abundantly expressed in tumors of various types, including melanoma. There are still sparse data regarding relationship of melanoma cell survivin expression with accepted histopathological characteristics as well as serum concentration. The aim of this study was to investigate the association of local tumor survivin expression (primary tumor and metastatic lesions) and serum concentration with clinical and histopathological parameters in melanoma patients. Methods. The level of survivin expression was determined immunocytochemically in tumor tissue and with ELISA test in the serum of 84 melanoma patients diagnosed from 2009 to 2013 at the Institute for Pathology and Forensic Medicine and Institute for Medical Research at Military Medical Academy, Belgrade, Serbia. Results. The intensity of survivin expression was significantly higher in the patients whose tumor had ulceration, higher mitotic index, higher Clark and Breslow stage, that made vascular invasion or spread through lymphatic vessels in primary tumor, and was significantly higher in the patients with metastatic disease. Survivin expression and the number of survivin positive cells in metastatic lesions were significantly associated with the duration of disease free interval (DFI). The patients with high expression score had almost double shorter DFI comparing to those with weak local survivin expression and a small number of surviving + cells (9 ± 7 vs 19 ± 13 months, respectively). The degree of tumor infiltrating lymphocytes presence in tumor tissue was significantly associated with serum survivin concentration, with lowest average level detected in samples of patients with the highest degree of infiltration. Serum survivin concentrations were highest in samples of melanoma patients with IA American Joint Commission on Cancer (AJCC) clinical stage, pT1a histological stage, patients whose tumors were still in horizontal growth phase, without signs of lympho-hematological disease spreading, with the highest number of mitoses and the smallest Clark index. Conclusion. Survivin expression in tumor tissue and its serum concetration significantly correlate with clinical and histopathological parameters. Serum levels could be important in initial follow-up as indicators of those patients that would have aggressive local tumor growth and spreading. Survivin determination in tumor tissue is of great significance in estimation of DFI.

	Reference
	Adamkov, M., Lauko, L., Balentova, S., Pec, J., Pec, M., Rajcani, J. (2009) Expression pattern of anti-apoptotic protein survivin in dysplastic nevi. Neoplasma, 56(2): 130-5
	Adamkov, M., Lauko, L., Rajčáni, J., Bálentová, S., Rybárová, S., Mištuna, D., Statelová, D. (2009) Expression of antiapoptotic protein survivin in malignant melanoma. Biologia, 64(4)
	Altień, D.C. (2003) Survivin in apoptosis control and cell cycle regulation in cancer. Prog Cell Cycle Res, 5: 447-52
1	Altieri, D.C. (2003) Survivin, versatile modulation of cell division and apoptosis in cancer. Oncogene, 22(53): 8581-9
	Andersen, M.H., Svane, I.M., Becker, J.C., Straten, P.T. (2007) The universal character of the tumor-associated antigen survivin. Clinical cancer research, 13(20): 5991-4
	Cohen, C., Lohmann, C.M., Cotsonis, G., Lawson, D., Santoianni, R. (2003) Survivin expression in ovarian carcinoma: correlation with apoptotic markers and prognosis. Modern pathology, 16(6): 574-83
	Colnaghi, R., Connell, C.M., Barrett, R.M.A., Wheatley, S.P. (2006) Separating the anti-apoptotic and mitotic roles of survivin. Journal of biological chemistry, 281(44): 33450-6
	Dadras, S.S. (2011) Molecular diagnostics in melanoma: current status and perspectives. Archives of pathology & laboratory medicine, 135(7): 860-9
	Ding, Y., Prieto, V.G., Zhang, P.S., Rosenthal, S., Smith, K.J., Skelton, H.G., Diwan, A. (2006) Nuclear expression of the antiapoptotic protein survivin in malignant melanoma. Cancer, 106(5): 1123-9
	Ellebaek, E., Iversen, T., Junker, N., Donia, M., Engell-Noerregaard, L., Met, Ö., Hölmich, L., Andersen, R., Hadrup, S., Andersen, M., Straten, P.thor, Svane, I. (2012) Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose Interleukin-2 in metastatic melanoma patients. Journal of Translational Medicine, 10(1): 169
	Fields, A.C., Cotsonis, G., Sexton, D., Santoianni, R., Cohen, C. (2004) Survivin expression in hepatocellular carcinoma: correlation with proliferation, prognostic parameters, and outcome. Modern Pathology, 17(11): 1378-1385
	Goksel, G., Taneli, F., Uslu, R., Ulman, C., Dinc, G., Coskun, T., Kandiloglu, A. (2007) Serum Her-2/neu and Survivin Levels and Their Relationship to Histological Parameters in Early-stage Breast Cancer. Journal of International Medical Research, 35(2): 165-172
	Grossman, D., McNiff, J.M., Li, F., Altieri, D.C. (1999) Expression and targeting of the apoptosis inhibitor, survivin, in human melanoma. Journal of investigative dermatology, 113(6): 1076-81
	Hadrup, S.R., Braendstrup, O., Jacobsen, G.K., Mortensen, S., Pedersen, L.Ø., Seremet, T., Andersen, M.H., Becker, J.C., Straten, P.T. (2006) Tumor infiltrating lymphocytes in seminoma lesions comprise clonally expanded cytotoxic T cells. International journal of cancer, 119(4): 831-8
	Hadrup, S.R., Gehl, J., Sørensen, R.B., Geertsen, P.F., Straten, P.T., Andersen, M.H. (2006) Persistence of survivin specific T cells for seven years in a melanoma patient during complete remission. Cancer biology & therapy, 5(5): 480-2
	Junker, N., Straten, P.thor, Andersen, M.H., Svane, I.M. (2011) Characterization of Ex Vivo Expanded Tumor Infiltrating Lymphocytes from Patients with Malignant Melanoma for Clinical Application. Journal of Skin Cancer, 2011: 1-6
	Junker, N., Munir, S., Kvistborg, P., Straten, P.thor, Svane, I.M., Andersen, M.H. (2012) A Promiscuous Survivin-Derived T-Cell Epitope Restricted to the HLA-A3 Super-Type Alleles. Journal of Investigative Dermatology, 132(8): 2115-2118
	Khan, S., Jutzy, J.M.S., Aspe, J.R., McGregor, D.W., Neidigh, J.W., Wall, N.R. (2011) Survivin is released from cancer cells via exosomes. Apoptosis, 16(1): 1-12
	Khan, S., Bennit, H.F., Turay, D., Perez, M., Mirshahidi, S., Yuan, Y., Wall, N.R. (2014) Early diagnostic value of survivin and its alternative splice variants in breast cancer. BMC Cancer, 14(1)
	McKenzie, J.A., Grossman, D. (2012) Role of the apoptotic and mitotic regulator survivin in melanoma. Anticancer research, 32(2): 397-404
	McKenzie, J.A., Liu, T., Goodson, A.G., Grossman, D. (2010) Survivin enhances motility of melanoma cells by supporting Akt activation and {alpha}5 integrin upregulation. Cancer research, 70(20): 7927-37
	McKenzie, J.A., Liu, T., Jung, J.Y., Jones, B.B., Ekiz, H.A., Welm, A.L., Grossman, D. (2013) Survivin promotion of melanoma metastasis requires upregulation of α5 integrin. Carcinogenesis, 34(9): 2137-44
	Nassar, A., Lawson, D., Cotsonis, G., Cohen, C. (2008) Survivin and Caspase-3 Expression in Breast Cancer: Correlation With Prognostic Parameters, Proliferation, Angiogenesis, and Outcome. Applied Immunohistochemistry & Molecular Morphology, 16(2): 113-120
	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. Histopathology, 50(7): 835-42
	Qi, Y., Li, X., Li, H., Zheng, Y. (2013) The Research of Nanocrystallized Realgar for the Treatment of Skin Cancer. Journal of Cancer Therapy, 04(06): 43-47
	Raimondo, S., Saieva, L., Corrado, C., Fontana, S., Flugy, A., Rizzo, A., de Leo, G., Alessandro, R. (2015) Chronic myeloid leukemia-derived exosomes promote tumor growth through an autocrine mechanism. Cell Communication and Signaling, 13(1): 8
	Reed, J.C. (2001) The Survivin saga goes in vivo. Journal of clinical investigation, 108(7): 965-9
	Reker, S., Becker, J.C., Svane, I.M., Ralfkiaer, E., Straten, P., Andersen, M.H. (2004) HLA-B35-restricted immune responses against survivin in cancer patients. International journal of cancer, 108(6): 937-41
	Schramm, S., Mann, G.J. (2011) Melanoma prognosis: a REMARK-based systematic review and bioinformatic analysis of immunohistochemical and gene microarray studies. Molecular cancer therapeutics, 10(8): 1520-8
2	Srinivasula, S.M., Ashwell, J.D. (2008) IAPs: what's in a name?. Molecular cell, 30(2): 123-35
	Takai, N., Miyazaki, T., Nishida, M., Nasu, K., Miyakawa, I. (2002) Survivin expression correlates with clinical stage, histological grade, invasive behavior and survival rate in endometrial carcinoma. Cancer letters, 184(1): 105-16
	Takeuchi, H., Morton, D.L., Elashoff, D., Hoon, D.S.B. (2005) Survivin expression by metastatic melanoma predicts poor disease outcome in patients receiving adjuvant polyvalent vaccine. International journal of cancer, 117(6): 1032-8
1	Tanaka, K., Iwamoto, S., Gon, G., Nohara, T., Iwamoto, M., Tanigawa, N. (2000) Expression of survivin and its relationship to loss of apoptosis in breast carcinomas. Clinical cancer research : an official journal of the American Association for Cancer Research, 6(1): 127-34
	Tas, F., Duranyildiz, D., Argon, A., Oguz, H., Camlica, H., Yasasever, V., Topuz, E. (2004) Serum bcl-2 and survivin levels in melanoma. Melanoma research, 14(6): 543-6
	Thomas, J., Liu, T., Cotter, M.A., Florell, S.R., Robinette, K., Hanks, A.N., Grossman, D. (2007) Melanocyte expression of survivin promotes development and metastasis of UV-induced melanoma in HGF-transgenic mice. Cancer research, 67(11): 5172-8
	Tsai, W., Chu, C., Yu, C., Sheu, L., Chen, A., Chiang, H., Jin, J. (2008) Matriptase and survivin expression associated with tumor progression and malignant potential in breast cancer of Chinese women: tissue microarray analysis of immunostaining scores with clinicopathological parameters. Disease markers, 24(2): 89-99
	Vetter, C.S., Müller-Blech, K., Schrama, D., Bröcker, E.B., Becker, J.C. (2005) Cytoplasmic and nuclear expression of survivin in melanocytic skin lesions. Archives of dermatological research, 297(1): 26-30

O članku

jezik rada: engleski
vrsta rada: izvorni naučni članak
DOI: 10.2298/VSP150519119J
objavljen u SCIndeksu: 05.11.2016.
metod recenzije: dvostruko anoniman

Povezani članci

Srps arh celokup lekarstvo (2013)
Analiza polimorfizma u promotoru gena za survivin kao mogućeg faktora rizika za nastanak tumora glave i vrata
Kostić Marija, i dr.

Serb J Anest Inten Therapy (2016)
Značaj survivina (BIRC5) kao biomarkera u preoperativnoj proceni kardiovaskularnog rizika kod nekardiohirurških operacija - survivin (BIRC5) kao novi srčani biomarker
Marković Danica, i dr.

J Med Biochemistry (2013)
Regulacija apoptoze preko inhibitora programirane ćelijske smrti
Marković Danica, i dr.