Kolorektal kanserlerde vitamin D reseptör ekspresyonunun kolorektal kanserlerde evre ile ilişkili ve prognoz üzerine etkisi

Yıl 2019, Cilt: 18 Sayı: 3, 101 - 108, 25.12.2019

Mehmet Sezgin Pepeler , Berna Savaş Merve Pamukcuoğlu Murat Törüner Hakan Akbulut

https://doi.org/10.17941/agd.601187

Cited By: 1

Öz

Amaç:  Kolorektal kanser  hücrelerinde vit D reseptör ekspresyonunun
tespiti ve bu reseptör ekspresyon derecesi ile kolorektal kanser  prognoz ve evresinin ilişkisi olup olmadığını
tespit etmektir. 

Yöntem ve Gereç: Çalışmaya 2003-2009
tarihleri arasında Ankara Üniversitesi Tıp Fakültesi (AÜTF)  Genel Cerrahi Bölümünde opere olmuş, AÜTF
Patoloji Bölümünde Kolon ve Rektum kanseri  (KRK) tanısı konulup medikal tedavisi AÜTF
Tıbbi Onkoloji Bölümünce yapılan hastalar dahil edilmiştir.Vit D reseptörlerinin değerlendirilmesi için
seçilen olguların Hematoksilen ve Eozin (H-E) kesitleri yeniden
değerlendirildi.

Bulgular:  Vit D reseptörü pozitif
olan hastalarda istatistiksel olarak anlamlı olmasa da medyan   sağkalım
reseptör negatif olanlara göre daha  iyi
bulunmuştur. Vitamin D reseptör (VDR)  pozitif olanlarda medyan sağkalıma
ulaşılamamıştır.5 yıllık sağkalım %69,4 oranında saptanmıştır. VDR negatif
olanlarda medyan sağkalım 60 ay saptanmıştır. 5 yıllık sağkalım %32 oranında
bulunmuştur. VDR pozitif ve negatif olanlar arasında medyan sağ kalım açısından
istatiksel olarak anlamlı fark saptanmamıştır(p:0,053). Hastalıksız sağkalım
için VDR'e göre anlamlı fark saptanmadı.VDR negatif olanlarda 5 yıllık
hastalıksız sağkalım  %56.8 bulunurken, VDR pozitif olanlarda  %43.3 bulunmuştur (Şekil 2.2). 

Sonuç: VDR ekspresyonunun KRK
prognozu üzerine olan etkisinin tek başına anlamlı olmadığı saptanmıştır. 
Reseptör ekspresyonu dışında reseptör polimorfizminin ve reseptörün etkilediği
yolaklarda rol oynayan mutasyonların da prognozu belirlemede etkili olabileceği
kanısına varılmıştır. 

Anahtar Kelimeler

Kolorektal karsinom, vitamin D reseptör pozitifliği, immunohistokimya

Kaynakça

• 1. Simboli-Campbell, M., et al., 1,25-Dihydroxyvitamin D3 translocates protein kinase C beta to nucleus and enhances plasma membrane association of protein kinase C alpha in renal epithelial cells. J Biol Chem, 1994. 269(5): p. 3257-64.2. Diaz, G.D., et al., Apoptosis is induced by the active metabolite of vitamin D3 and its analogue EB1089 in colorectal adenoma and carcinoma cells: possible implications for prevention and therapy. Cancer Res, 2000. 60(8): p. 2304-12. 3 . Haussler, M.R., et al., The nuclear vitamin D receptor: biological and molecular regulatory properties revealed. J Bone Miner Res, 1998. 13(3): p. 325-49.4 Barsony, J., et al., Immunocytology with microwave-fixed fibroblasts shows 1 alpha,25-dihydroxyvitamin D3-dependent rapid and estrogen-dependent slow reorganization of vitamin D receptors. J Cell Biol, 1990. 111(6 Pt 1): p. 2385-95.5 Fedirko, V., et al., Effects of supplemental vitamin D and calcium on oxidative DNA damage marker in normal colorectal mucosa: a randomized clinical trial. Cancer Epidemiol Biomarkers Prev, 2010. 19(1): p. 280-916 Freedman, L.P., Transcriptional targets of the vitamin D3 receptor-mediating cell cycle arrest and differentiation. J Nutr, 1999. 129(2S Suppl): p. 581S-586S.7 Zehnder, D., et al., Extrarenal expression of 25-hydroxyvitamin d(3)-1 alpha-hydroxylase. J Clin Endocrinol Metab, 2001. 86(2): p. 888-94.8 Hsu, J.Y., et al., Reduced 1alpha-hydroxylase activity in human prostate cancer cells correlates with decreased susceptibility to 25-hydroxyvitamin D3-induced growth inhibition. Cancer Res, 2001. 61(7): p. 2852-6.9 Friedrich, M., et al., Analysis of 25-hydroxyvitamin D3-1alpha-hydroxylase in normal and malignant breast tissue. Anticancer Res, 2006. 26(4A): p. 2615-20.10 Matusiak, D., et al., Expression of vitamin D receptor and 25-hydroxyvitamin D3-1{alpha}-hydroxylase in normal and malignant human colon. Cancer Epidemiol Biomarkers Prev, 2005. 14(10): p. 2370-6.11 Lointier, P., et al., The role of vitamin D3 in the proliferation of a human colon cancer cell line in vitro. Anticancer Res, 1987. 7(4B): p. 817-21.12 Shabahang, M., et al., 1,25-Dihydroxyvitamin D3 receptor as a marker of human colon carcinoma cell line differentiation and growth inhibition. Cancer Res, 1993. 53(16): p. 3712-8.13 Sheinin, Y., et al., In situ mRNA hybridization analysis and immunolocalization of the vitamin D receptor in normal and carcinomatous human colonic mucosa: relation to epidermal growth factor receptor expression. Virchows Arch, 2000. 437(5): p. 501-7.14 Elloul, S., et al., Snail, Slug, and Smad-interacting protein 1 as novel parameters of disease aggressiveness in metastatic ovarian and breast carcinoma. Cancer, 2005. 103(8): p. 1631-43.15 Otani, T., et al., Plasma vitamin D and risk of colorectal cancer: the Japan Public Health Center-Based Prospective Study. Br J Cancer, 2007. 97(3): p. 446-51.16 Grau, M.V., et al., Vitamin D, calcium supplementation, and colorectal adenomas: results of a randomized trial. J Natl Cancer Inst, 2003. 95(23): p. 1765-71.17 Wactawski-Wende, J., et al., Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med, 2006. 354(7): p. 684-96.18 Garland, C.F., et al., Serum 25-hydroxyvitamin D and colon cancer: eight-year prospective study. Lancet, 1989. 2(8673): p. 1176-819 Cross, H.S., et al., Growth control of human colon cancer cells by vitamin D and calcium in vitro. J Natl Cancer Inst, 1992. 84(17): p. 1355-7.20 Hulla, W., et al., Growth control of human colon-adenocarcinoma-derived Caco-2 cells by vitamin-D compounds and extracellular calcium in vitro: relation to c- myc-oncogene and vitamin-D-receptor expression. Int J Cancer, 1995. 62(6): p. 711-6.21 Matusiak, D., et al., Expression of vitamin D receptor and 25-hydroxyvitamin D3-1{alpha}-hydroxylase in normal and malignant human colon. Cancer Epidemiol Biomarkers Prev, 2005. 14(10): p. 2370-6.22 Deeb, K.K., D.L. Trump, and C.S. Johnson, Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. Nat Rev Cancer, 2007. 7(9): p. 684- 700.23 Zhang, Y., J. Zhang, and G.P. Studzinski, AKT pathway is activated by 1, 25-dihydroxyvitamin D3 and participates in its anti-apoptotic effect and cell cycle control in differentiating HL60 cells. Cell Cycle, 2006. 5(4): p. 447-51.24 Hughes, P.J. and G. Brown, 1Alpha,25-dihydroxyvitamin D3-mediated stimulation of steroid sulphatase activity in myeloid leukaemic cell lines requires VDRnuc- mediated activation of the RAS/RAF/ERK-MAP kinase signalling pathway. J Cell Biochem, 2006. 98(3): p. 590-617.25 Kure, S., et al., Vitamin D receptor expression is associated with PIK3CA and KRAS mutations in colorectal cancer. Cancer Epidemiol Biomarkers Prev, 2009. 18(10): p. 2765-72.26 Thomas, M.G., et al., Vitamin D receptor expression in colorectal cancer. J Clin Pathol, 1999. 52(3): p. 181-3.27 Meggough F, L.P., Saez S, Sex steroid and 1,25-dihydroxy vitamin D3 receptors in human colorectal adenocarcinoma and normal mucosa. Cancer Res 1991. 5: p. 1227-30.28 Kane, K.F., M.J. Langman, and G.R. Williams, 1,25-Dihydroxyvitamin D3 and retinoid X receptor expression in human colorectal neoplasms. Gut, 1995. 36(2): p. 255-8.29 Meggough F, Lointier P, Pezet D, Saez S; Evidence of 1,25-dihydroxyvitamin D3-receptors in human digestive mucosa and carcinoma tissue taken at different levels of digestive tract, in 152 patients, J Steroid Biochem, 1990 Jun; 36(1-2):143-730 Lointier P, Meggough F, Dechelotte P, Pezet D, Ferrier C, Chipponi J, Saez S; 1,25-Dihydroxyvitamin D3 receptors and human colon adenocarcinoma Br J Surs; 1991 Apr; 78(4):435-931 Welsh, J., Vitamin D and breast cancer:insights from animal models. American Journal of Clinical Nutrition, 2004. 80(6): p. 1721-1724. and Malignant Breast Tissue. Anticancer Research, 2009. 29: p. 155-158.32 Stephanie L. Hines, M.D., H. Keels S. Jorn, M.D., Kristine M. Thompson, M.D., and Jan M. Larson, M.D. , Breast cancer survivors and vitamin D: A review. Nutrition, 2010. 26: p. 255-262.33 Rebecca Suk Heist, W.Z., Zhaoxi Wang, Geoffrey Liu, Donna Neuberg, Li Su, Kofi Asomaning, and T.J.L. Bruce W. Hollis, John C. Wain, Edward Giovannucci, and David C. Christiani, Circulating 25-Hydroxyvitamin D, VDR Polymorphisms,and Survival in Advanced Non–Small-Cell Lung Cancer. journal of clinical oncology, 2008. 26: p. 34.34 Martin Blomberg Jensena, C.B.A., John E. Nielsena, Per Bagic, and A.J. Anne Jørgensena, Henrik Leffers Expression of the vitamin D receptor, 25-hydroxylases, 1-hydroxylase and 24-hydroxylase in the human kidney and renal clear cell cancer. Journal of Steroid Biochemistry & Molecular Biology, 2010. 121: p. 37382.35 Cross, H.S., et al., The Vitamin D endocrine system of the gut--its possible role in colorectal cancer prevention. J Steroid Biochem Mol Biol, 2005. 97(1-2): p. 121- 8.