Meme Kanserinde Survivin İfadesinin Tamoksifen Direncine Etkisi
İsa Dede1*, Hakan Akbulut2, Ayça Karabörk3, Şirin Çetin4
1Mustafa Kemal University, Hatay, Turkey
2Ankara University, Ankara, Turkey
3Ankara University, Ankara, Turkey
4Tokat Gaziosmanpaşa University, Tokat, Turkey
* Corresponding author: drdede@mynet.com
Presented at the 4th International Symposium on Innovative Approaches in Health and Sports Sciences (ISAS WINTER-2019 (HSS)), Samsun, Turkey, Nov 22, 2019
SETSCI Conference Proceedings, 2019, 12, Page (s): 60-66 , https://doi.org/10.36287/setsci.4.9.046
Published Date: 23 December 2019
Survivin antiapoptotik bir proteindir. Embriyonik yaşamda ve birçok tümördeyüksek düzeyde eksprese olmasına rağmen normal dokularda bulunmaz. Meme kanseri kadınlarda en sık görülen malignitedir. Meme kanserinin standart tedavisi kemoterapi, estrojen reseptörü pozitif olan hastalarda endokrin tedavi ve HER-2 pozitif hastalıkta trastuzumab tedavilerinin birlikte veya ardışık uygulanmasıdır. Fakat bazı hastalarda endokrin tedaviye karşı direnç gelişmektedir. Bu çalışmamızda amaç survivin ekspresyonunun tamoksifen direncine olan etkisini değerlendirilmektir. 2004-2011 yılları arasında Ankara Üniversitesi Tıp Fakültesi Onkoloji Bilim dalında meme kanseri tanısı ile adjuvan tamoksifen kullanan hastalar çalışmaya alındı. Tamoksifen duyarlı ve dirençli her iki grup da 25’er hasta incelendi. Survivin ekspresyonu survivin antikorları kullanılarak immunhistokimyasal olarak değerlendirildi. Nükleer vesitoplazmik survivin ekspresyonları boyanma yüzdesine göre derecelendirildi. Tamoksifene dirençli grup da nükleer boyanma, tamoksifen duyarlı gruptakine göre anlamlı olarak daha fazla bulunurken (p=0.045). Sitoplazmik boyanma tamoksifen duyarlı grupda daha fazla fakat anlamlı bir fark bulunamadı (p=0.544). Nükleer survivin overekspresyonunun, tamoksifen tedavi seçiminde bir belirteç olabileceğini düşünüyoruz. Ancak bu konunun daha fazla hasta sayısı ile yapılacak çalışmalar ile aydınlatılmasına ihtiyaç vardır. Survivinin tamoksifenin indüklediği apoptozisi engelleyerek bu etkisini göstermiş olabileceğini düşünüyoruz. Keywords – : survivin, immunhistokimya, tamoksifen direnci Abstract, Role of Survivin Expression İn Tamoxifen Resistance İn Patient With Early Breast Cancer Survivin is an anti-apoptotic protein. Survivin is expressed during embryonic life and in many tumors but not in normal tissue. Breast cancer is the most common malignant tumor in women. Adjuvant tamoxifen is one of the basic endocrine treatment modalities for the operable patients with estrogen receptor positive breast cancer. However, some of the patients are resistant to tamoxifen. In the current study we aimed to evaluate the role of surviving expression in tamoxifen resistance in patients with early breast cancer. A total of consecutive fifty patients with early breast cancer diagnosed and treated between 2004 and 2011 in Ankara University School of Medicine included in the study. Patients were divided into two groups namely tamoxifen resistant (25 patients) and tamoxifen sensitive (25 patients). Nuclear and cytoplasmic survivin expression was evaluated by immunohistochemical staining. The survivin expression level was regarded as low in patients with no or less than 5% staining. The nuclear surviving expression was significantly higher in tamoxifen-resistant patients when compared to the sensitive ones (p=0.045). Though not significant, the cytoplasmic surviving staining was more prominent in tamoxifen-sensitive patients (p=0.544). In conclusion, nuclear survivin expression seems to be related with tamoxifen resistance and a favorable prognostic factor in patients with early breast cancer.
Keywords - survivin, immunhistokimya, tamoksifen direnci survivin, immunohistochemistry, tamoxifen resistance
1. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005;365:1687-1717
2. Chang M, Liu H, Jordan VC. Hormone and Growth Factor Receptors. In: Donegan WL, Priatt J.S. (eds). Cancer of the Breast, 5th ed. Philadelphia: PA Saunders 2002;417-441.
3. Lacey JV Jr, Kreimer AR, Buys SS, Marcus PM, Chang SC, Leitzmann MF, Hoover RN, Prorok PC, Berg CD, Hartge P. Breast cancer epidemiology according to recognized breast cancer risk factors in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial Cohort, BMC Cancer 2009;9: 8
4. Tavasoli FA, Devilee P. World Health Organition Classification of Tumours. Pathology and Genetics: Tumours of the Breast and Female Genital Organs. pp. 9-112. Lyon, IARC Pres,2003.
5. Hrstka R, Brychtova V, Fabian P, Vojtesek B, Svoboda M. AGR2 predicts tamoxifen resistance in postmenopausal breast cancer patients. Disease Markers 2013; 35(4): 207-212 .
6. V. Craing Jordan and Bert W. O’Malley. Selective Estrogen Modulators and Antihormonal Resistance in Breast Cancer. J of Clin Oncol 2007; Decem vol 25, 5815-24.
7. Ryosuke M, Naoki T, Mikako M, Daisuke K, Naoki T Survivin plays as a resistant factor against tamoxifen-induced apoptosis in human breast cancer cells. Breast cancer Res Treat (2009) 117: 261-271.
8. Tetsuhisa Y, Nobuhiko T.: The role of survivin as a new target of diagnosis and treatment in human cancer. Med Electron Microsc, 2001; 34: 12-20.
9. Altieri DC.:Validating survivin as a cancer therapeutic target. Nat Rev Cancer, 2003; 3: 46-54.
10. Dario C. Altieri. Survivin in apoptosis control and cell cycle regulation in cancer. Progress in Cell Cycle Research, Vol. 5, 447-452, (2003) .
11. Zhang SQ, Qiang SY, Yang WB, Jiang JT, Ji ZZ Expression of survivin in different stages of carcinogenesis and progression of breast cancer. 2004; 23:697-700 Chinese.
12. EBCTOG: Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: An overview of the randomised trials. Lancet 365: 1687-1717,2005.
13. Hong SE, Kim EK, Jin HO, Kim HA, Lee JK, Koh JS, Seol H, Kim JI, Park IC, Noh WC. S6K1 inhibition enhances tamoxifen-induced cell death in MCF-7 cells through translational inhibition of Mcl-1 and survivin. Cell Biol Toxicol. 2013 Aug; 29(4):273-82.
14. Span PN, Tjan-Heijnen VC, Manders P, Van Tienoven D, Lehr J, Sweep FC. High survivin predicts a poor response to endocrine therapy, but good response to chemotherapy in advanced breast cancer. Breast Cancer Res Treat 2006 Jul; 223-30.
15. Kumkum Jha, Mndula Shukla, Manoi Pandey. Survivin expression and targeting in breast cancer. Surgical Oncology. 2012; 21(2):125-131.
16. Jan-Show Chu, Jin-Yuh Shew, Chiun-Sheng Huang. Immunohischemical analysis of survivin expression in primary breast cancers. Journal of the Formosan Medical Association 2005;103(12): 925-931.
17. Shın-Ichı Y, Yoshika M, Takashi K, Yoshio H, Toshihiko M, Satoshi I, Mirei K, Shinsuke T, Katsunobu K. Survivin Expression Predicts Early Recurrence in Early-stage Breast Cancer. Anticancer Research. 2007; 27:2803-2808.
18. Nermeen S, Youssef, Iman H. Hewedi, Nermine M. Immunohistochemical Expression of Survivin in Breast Carcinoma: Relationship with Clinopathological Parameters, Proliferation and Molecular Classification. Journal of the Egyptian Nat. Cancer Inst. 2008;20(4), 348-357.
19. Al-Joudi F S, Iskandar Z A, Hasnan J, Rusli J, Kamal Y, Imran A K, Ahmed M, Zakaria J. Expression of survivin and its clinicopathological correlations in invasive ductal carcinoma of the breast. Singapore Med J 2007; 48(7): 607-14.
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