Aynur Albayrak SÖNMEZ, Berrak Gümüşkaya ÖCAL, Sema HÜCÜMENOĞLU, Murat ALPER, Murat OKTAY

Prostat Adenokarsinomlarında Annexin A2, A7 Ve A11 İmmünhistokimyasal Ekspresyonu ve Prognostik Faktörlerle İlişkisi

Amaç: Bu çalışmada kalsiyum bağımlı fosfolipid bağlayan proteinler olan Annexin ailesininüyelerinden Annexin A2, A7 ve A11’in prostat adenokarsinomu gelişimi ve ilerlemesi üzerindekirolü araştırıldı.Yöntem: 53 adet prostat adenokarsinomu olgusunda çevre normal doku ve karsinom dokularınıniyi temsil edildiği kesitlerde immünhistokimyasal olarak Annexin A2, A7 ve A11 ekspresyonu,çevre normal dokudan farkı ve tümör evresi, tümör derecesi ve diğer prognostik kriteler ileilişkisi değerlendirildi.Bulgular: Hücre homeostasisinde, membran fonksiyonlarının düzenlenmesinde ve hücreçoğalmasında etkileri olduğu bilinen Annexin A2, A7 ve A11’in normal prostat dokularındagüçlü sitoplazmik ekspresyon gösterdiği ancak prostat adenokarsinomlarında, tümörsüz çevredokuya oranla anlamlı olarak azalmış ekspresyon gösterdiği saptanmıştır ( sırası ile p=0,022;0,028; 0,033) . Gleson skor, yaş, evre, kapsül invazyonu ve perinöral invazyon ile anlamlı ilişkibulunmamıştır.Sonuç: Prostat adenokarsinom hücrelerinde gözlenen Annexin A2, A7, A11 ekspresyonazalmasının, tümör hücrelerinin diferansiasyon kaybı ve invazyon yeteneği kazanması ile ilişkiliolduğu düşünülmüştür. Ayrıca özellikle Annexin A2’nin prostat adenokarsinomunun normaldokudan ayırıcı tanısında immunhistokimyasal bir yardımcı olarak kullanılabileceğibelirlenmiştir

Anahtar Kelimeler:

Prostat adenokarsinomu, Annexin A2, Annexin A7, Annexin A11, immunhistokimya, karsinogenez

Annexin A2, A7 and A11 Immunohistochemical Expression in Prostate Adenocarcinoma and Relationship with Prognostic Factors

Purpose: The role of calcium dependent phospholipase binding protein family membersAnnexin A2, A7 and A11 in the development and progression of prostate cancer was explored.Methods: Protein expressions of Annexin A2, A7 and A11 were examined byimmunohistochemistry in 53 clinicopathologically characterized prostate cancer and peritumoralareas. Difference between cancer and normal tissues was evaluated and relationship withprognostic factors was determined.Results: The expression of Annexin A2, A7 and A11, effect regulation of membrane functions,cellular homeostasis, and proliferation, were down-regulated in prostate cancer compared withadjacent non-cancerous tissues ( respectively p=0,022; 0,028; 0,033). Expression of annexina2, a7 and a11 did not correlate with age, stage, invasion of capsule and perineural tissue.Conclusion: the decrease of expression of Annexin A2, A7 and A11 protein in prostateadenocarcinoma can associate with acquired capability of invasion and loss of differentiationof tumor cells. Annexin A2 can used as immunohistochemical helper in differential diagnosisbetween normal and carcinomatous tissues on biopsy

Keywords:

Prostate adenocarcinoma, Annexin A2, Annexin A7, Annexin A11, immunohistochemistry, carcinogenesis,

PDF

___

Gerke V, Creutz CE, Moss SE. Annexins: linking Ca2+ signalling to membrane dynamics. Nat Rev Mol Cell Biol 2005; 6(6): 449–461.

Frohlich M, Motte P, Galvin K, Takahashi H, Wands J, Ozturk M. Enhanced expression of the protein kinase substrate p36 in human hepatocellular carcinoma. Mol Cell Biol 1990; 10(6): 3216–3223.

Dreier R, Schmid KW, Gerke V, Riehemann K. Differential expression of annexins I, II and IV in human tissues: an immunohistochemical study. Histochem Cell Biol 1998; 110(2): 137–148.

Massey-Harroche D, Mayran N, Maroux S. Polarized localizations of annexins I, II, VI and XIII in epithelial cells of intestinal, hepatic and pancreatic tissues. J Cell Sci 1998; 111(Part 20): 3007– 3015.

Chetcuti A, Margan SH, Russell P, Mann S, Millar DS, Clark SJ, Rogers J, Handelsman DJ, Dong Q. Loss of annexin II heavy and light chains in prostate cancer and its precursors. Cancer Res 2001; 61(17): 6331– 6334.

Banerjee AG, Liu J, Yuan Y, Gopalakrishnan VK, Johansson SL, Dinda AK, Gupta NP, Trevino L, Vishwanatha JK. Expression of biomarkers modulating prostate cancer angiogenesis: differential expression of annexin II in prostate carcinomas from India and USA. Mol Cancer 2003; 2: 34.

Liu JW, Shen JJ, Tanzillo-Swarts A, et al. Annexin II expression is reduced or lost in prostate cancer cells and its re-expression inhibits prostate cancer cell migration. Oncogene 2003; 22(10): 1475–1485.

Gillette JM, Chan DC, Nielsen-Preiss SM. Annexin 2 expression is reduced in human osteosarcoma metastases. J Cell Biochem 2004; 92(4): 820–832

Zhi H, Zhang J, Hu G, Lu J, Wang X, Zhou C, Wu M, Liu Z. The deregulation of arachidonic acid metabolism-related genes in human esophageal squamous cell carcinoma. Int J Cancer 2003; 106(3): 327–333

Pena-Alonso E, Rodrigo JP, Parra IC, et al. Annexin A2 localizes to the basal epithelial layer and is down-regulated in dysplasia and head and neck squamous cell carcinoma. Cancer Lett 2008, 263(1): 89–98.

Yee D, Narula N, Ramzy I et al. Ornstein, MD. Reduced Annexin II Protein Expression in High-Grade Prostatic Intraepithelial Neoplasia and Prostate CancerArch Pathol Lab Med 2007, 131, 902-908.

Raynal P, Pollard HB: Annexins: The problem of assessing the biological role for a gene family of multifunctional calcium- and phospholipid-binding proteins. Biochim Biophys Acta 1994, 1197:63–93.

Nir S, Stutzin A, Pollard HB: Effect of synexin on aggregation and fusion of chromaffin granule ghosts at pH 6. Biochim Biophys Acta 1987, 903:309–318.

Pollard HB, Rojas E, Burns AL: Synexin (ANXA7) and membrane fusion during the process of exocytotic secretion. Prog Brain Res 1992, 92:247–255.

Palmer RE, Lee SB, Wong JC, et al.: Induction of BAIAP3 by the EWS-WT1 chimeric fusion implicates regulated exocytosis in tumorigenesis. Cancer Cell 2002, 2:497–505.

Strivastava M, Atwater I, Glasman M,et al. Defects in inositol 1,4,5-triphophate receptor expression,Ca(2+) signaling, and insulin secretion in the ANX A7 (+/-)knockout mouse. Proc Natl Acad Sci USA 1999, 96:13783-13788.

Srivastava M, Montagna C, Leighton X, et al. Haploinsufficiency of ANXA7 tumor suppressor gene and consequent genomic instability promotes tumorigenesis in the ANXA7(+/-) mouse. Proc Natl Acad Sci USA 2003, 100:14287–14292.

Pıng-ı H, Mıng-Shyan H,The significance of ANX A7 expression and its correlation with poor cellular differentiation and enhanced metastatic potential of gastric cancer. J Surg Oncol 2008, 97:609-614.

Srivasta M, Torosyan Y, Raffeld M, et al. ANX a7 expression represents hormone-relevant tumor suppression in different cancers. Int J Cancer; 121:2628-2636. 2007

Srivastava M, Bubendorf L, Srikantan V, et al. ANX7, a candidate tumor suppressor gene for prostate cancer. Proc Natl Acad Sci U S A. 2001, 98(8):4575-80. 2001

Tomas A, Moss SE, Calcium and cell cycle dependent association of annexin 11 with the nuclear envelope. J Biol Chem 2003, 278:20210-20216.

Tomas A, Clare F, Moss SE, Annexin 11 is required for midbody formation and completion of the terminal phase of cytokinesis. J Cell Biol 2004, 165:813-822.

Song J, Shih IeM, Salani R, Chan DW, Zhang Z. Annexin XI is associated with cisplatin resistance and related to tumor recurrence in ovarian cancer patients. Clin Cancer Res 2007, 13:6842-9.

Xin W, Rhodes DR, Ingold C, Chinnaiyan AM, Rubin MA. Dysregulation of the annexin family protein family is associated with prostate cancer progression. Am. J. Pathol 2003, 162:255-61.