İbrahim SARI, ZEHRA BOZDAĞ, İLKER SEÇKİNER, Haluk ŞEN

Mesanenin ürotelyal karsinomlarında maspin ekspresyonunun tümör derece ve evresi ile ilişkisi

Amaç: Mesanenin ürotelyal karsinomlarında maspin’in immünhistokimyasal yöntemle ekspresyon’u araştırılmış, klinikopatolojik parametreler ile ilişkilerinin incelenmesi amaçlanmıştır.Giriş: Maspin serpin (serin proteaz inhibitörü) ailesinin bir üyesidir ve çeşitli tümör tiplerinde, tümör büyümesi ve anjiyogenez inhibitörü olduğu ve metastazı baskılayıcı olduğu gösterilmiştir. Mesane tümörlerinde prognozu belirleyen en önemli faktörler, tümörün histolojik derecesi ve evresidir.Gereç ve Yöntemler: Çalışmaya alınan örnekler, 2005-2011 yılları arasında transüretral rezeksiyon-mesane (TUR-M) yapılarak Gaziantep Üniversitesi Tıp Fakültesi Patoloji Anabilim Dalı tarafından ürotelyal karsinom tanısı almış 67 vakadan oluşuyordu. Vakalar DSÖ/ISUP 2004 derecelendirme sistemine göre 3’ü DMPPÜN, 25’i DDÜK, 39’ı YDÜK olarak sınıflandırıldı. Patolojik evreleme sistemine göre 35 pTa, 17 pT1, 12 pT2, 1 pT3, 2 pT4 vakadan oluşmakta idi. Çalışmamızda histolojik derece ile invazyon ve pT evre arasında anlamlı derecede bir ilişki bulundu. Histolojik derece arttıkça invazyon ve pT evre anlamlı olarak artış göstermekteydi (p=0,001). Bulgular: Çalışmamızda 57 (%85,1) tümör olgusu maspin pozitifliği gösterdi. Maspin ekspresyon seviyesine göre 4 olgu (%6) +1, 26 olgu (%38.8) +2, 27 olgu (%40.3) +3 olarak dağılım gösterdi. Maspin pozitifliği istatistiksel olarak anlamlı olmasa da noninvaziv ve düşük dereceli olgularda daha fazla idi. Maspin ekspresyon seviyesi dikkate alındığında histolojik derece ve pT evre ile anlamlı ilişkili saptandı (p=0,009, p=0.020). Maspin ekspresyon skoru pT evre ve histolojik derece ile anlamlı negatif korelasyon saptandı (r=-0.283, p=0.020) (r=-0.316, p=0.009). Maspin ekspresyon ile tümör rekürrensi ve tümör nedenli ölüm arasında anlamlı bir korelasyona rastlanmadı (p =0,933,p=0.208).Sonuç: Mesane ürotelyal karsinomlarında maspin ekspresyonu düşük derece ve evre ile ilişkilidir. Bulgularımız mesane tümörlerinde maspin ekspresyonunun değerlendirilmesinin tümörün davranışının tahmininde yararlı bir prognostik belirleyici olabileceğini düşündürmektedir.

Anahtar Kelimeler:

Mesane ürotelyal karsinomu, maspin, immünhistokimya

The relationship of maspin expression with tumor grade and stage in urothelial carcinomas of the urinary bladder

AbstractObject: In this study we aimed to investigate maspin expressions by immunhistochemistry in bladder urothelial carsinomas and to examine the relationship with clinicopathologic parameters.Introduction: Maspin is a member of the serpin (serine protease inhibitor) family and has been shown to be a suppressor of tumor growth and an inhibitor of angiogenesis as well as metastasis in several types of tumors. The most important factors in determining the prognosis in the urinary bladder tumors are the histological grade and stages. Material and Methods: The samples were obtained from the 67 cases underwent transurethral resection-bladder(TUR-B) between the 2005-2011, which diagnosed with urothelial carcinomas at Gaziantep University School of Medicine Department of Pathology. The cases according to the WHO / ISUP 2004 grading system were; 3 PUNLMP, 25 LGUC, 39 HGUC.Results:They are distributed as 35 pTa, 17 pT1, 12 pT2, 1 pT3, 2 pT4 according to pathologic staging. Histologic grading was significantly related with invasion and pT staging. As the histologic grade was increased, invasion and pT staging were increased significantly (p=0,001). In this study, 57 (%85,1) tumoral cases were positive for maspin. According to maspin expression level, the cases were classified as 4 (%6) 1+, 26 (%38.8) 2+, 27 (%40.3) 3+. Although it was not statistically significant, maspin positivity was higher in noninvasive and low grade tumors. Considering maspin expression level, it was significantly associated with histologic grading and pT staging (p=0,009, p=0.020). Maspin expression score was significantly negatively correlated with pT staging and histologic grading (r=-0.283, p=0.020) (r=-0.316, p=0.009). There was no correlation between the maspin expression and tumor recurrence and tumorrelated death (p =0,933,p=0.208). Conclusion:According to our results, maspin expression seems to be related with lower histologic grade and stage in bladder urothelial carsinomas. Our findings suggested that the evaluation of maspin expression in bladder tumors is useful prognostic marker for predicting the tumor behavior.

Keywords:

Bladder Urothelial carcinomas, Maspin, Immunohistochemistry,

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1. K. Lindemann - Docter, R Knüchel - Clarke. Histopathologie des Harnblasen karzinoms, instıtut für pathologie. Universitat klinikum Aachen. Urologie 2008;47:627-38.
2. Hendricksen K, Witjes JA. Treatment of intermediate-risk non-muscle-invasive bladder cancer (NMIBC). Eur Urol 2007;6: 800-08.
3. Herr HW. Tumor progression and survival of patients with high grade, noninvasive papillary (TaG3) bladder tumors: 15-year outcome. J Urol 2000;163:60-2.
4. Bostwick DG, Mikuz G. Urothelial papillary (exophytic) neoplasms, Virchows Arch 2002;441:109- 16.
5. Hansen AB, Bjerregaard B, Ovesen H, Horn T. AgNOR counts and histological grade in stage pTa bladder tumours: reproducibility and relation to recurrence pattern. Histopathology 1992; 20:257-62.
6. Sorensen FB, Sasaki M, Fukuzawa S. Qualitative and quantitative histopathology in transitional cell carcinomas of the urinary bladder. An international investigation of intra- and interobserver reproducibility. Lab Invest 1994;70:242-54.
7. Pich A, Chiusa L, Comino A, Navone R. Cell proliferation indices, morphometry and DNA flow cytometry provide objective criteria for distinguishing low and high grade bladder carcinomas. Virchows Arch 1994; 424:143-48.
8. Wu TT, Chen JH, Lee YH, Hang JK. The role of bcl-2, p53, and Ki-67 index in predicting tumor recurrence for low grade superficial transitional cell bladder carcinoma, J Urol 2000; 163:758-60.
9. Oge O, Erdem E, Atsu N, Ahin A, Ozen H, Ozen H. Proposal for changes in cystoscopic follow-up patients with lowgrade pTa bladder tumor. Eur Urol 2000; 37: 271-74.
10. EL-Maqsoud NMR, Tawfıek ER. Loss of Maspin Expression in Bladder Cancer: Its Relationship with p53 and Clinicopathological Parameters. J Egyptian Nat Cancer Inst 2010; 22: 1-12.
11. Cao D, Zhang Q, Wu LS, Abruzzese JL, Maitra A, Ho L. Prognostic significance of maspin in pancreatic ductal adenocarcinoma: tissue microarray analysis of 223 Surgically resected cases. Mod Pathol 2007; 520: 570-78.
12. Blandamura S, D’Alessandro E, Giacomelli L et al. Expression of Maspin in Papillary Ta/T1 Bladder Neoplasms. Anticancer Research 2008; 28: 471-78.
13. Zhang M, Volpert O, Shi YH, Bouck N. Maspin is an angiogenesis inhibitor. Nat Med 2000; 6: 196-9.
14. Zou Z, Zhang W, Young D et al. Maspin expression profile in human prostate cancer (CaP) and in vitro induction of Maspin expression by androgen ablation. Clin Cancer Res 2002; 8: 1172-77.
15. Song SY, Lee SK, Kim DH et al. Expression of maspin in colon cancers: its relationship with p53 expression and micro vessel density. Dig Dis Sci 2002; 47: 1831-35.
16. Xia W, Lau YK, Hu MC et al. High tumoral maspin expression is associated with improved survival of patients with oral squamous cell carcinoma. Oncogene 2000; 19: 2398- 403.
17. Sugimoto S, Mass N, Takimoto Y et al. Expression and regulation of tumor suppressor gene Maspin in human bladder cancer. Cancer Letters 2004; 203: 209-215.
18. Friedrich GM, Toma IM, Petri S et al. Expression of Maspin in non-muscle invasive bladder carcinoma: correlation with tumor angiogenesis and prognosis. Eur Urol 2004; 45: 737-43.
19. Kirkali Z, Cihan T, Manoharan M et al. Bladder cancer: epidomiology, staging and grading and diagnosis. Urology 2005;66:4-34.
20. Tetsuya I, Kiyoshi K, Yoshio E, Tadao U, Takuma S, Mikio N. Dominant role of E-cadherin in the progression of bladder cancer. J Urol 1999;161:692-98.
21. Sexton JW, Wiegand RL, Correa J, Politis C, Dickinson IS, Kang CL. Bladder Cancer: A Review of Non-Muscle Invasive Disease. Cancer Control 2010; 17: 256-68.
22. Diaz De ST, Segersten U, Malmström PU. Molecular genetics of bladder cancer: an update. Minerva Urol Nefrol 2008; 60: 205-16.
23. Seitz M, Zaak D, Knüchel-Clarke R, Stief C. Harnblasentumoren Die neu WHO Klassifikation 2004. Urology 2005; 44: 1073-86.
24. Reuter E. Victor, The pathology of Bladder Cancer. Urology 2006; 11-18.
25. Carbin BE, Ekman P, Gustafson H, Christensen Nj, Sandstedt B, Silfversward C. Grading of human urothelial carcinoma based on nuclear atypia and mitotic frequency: Histological description. J Urol 1991;145:968-71.
26. Jakse G, Loidl W, Seeber G, Hofstadter F. Stage 1, grade 3 transitional cell carcinoma of the bladder: an unfavourable tumor. J Urol 1987;137:39-44.
27. Jordan AM, Weingarten J, Murphy WM. Transitional cell neoplasms of the urinary bladder: can biologic potential be predicted from histologic grading? Cancer 1987;60:2766- 74.
28. Lipponen PK, Eskelinen MJ, Jauhiainen K, Harju E, Terho R, Haapasalo H. Prognostic factors in nodular transitional cell bladder tumors. Scand J Urol Nephrol 1993;27:205-10.
29. Murphy WM. ASCP survey on anatomic pathology examination of the urinary bladder. Am J Clin Pathol 1994;102:715-23.
30. Pauwels RPE, Schapers RFM, Smeets AWGB, Debruyne FM, Geraedts JP. Grading in superficial bladder cancer. Morphological criteria. Br J Urol 1988;61:129-134.
31. Takashi M, Sakata T, Murase T, Hamajima N, Miyake K. Grade 3 bladder cancer with lamina propria invasionpT1:characteristics of tumor and clinical course. Nagoya J Med Sci 1991;53:1-8.
32. Teoh SYS, Whisstock JC, Brid IP. Maspin (SERPINB5) Is an Obligate Intracellular Serpin. J Biol Chem 2010; 285(14): 10862-869.
33. Cheng Liang, Montironi R, Davidson DD, Lopez-Beltran A. Staging and reporting of urothelial carcinoma of the urinary bladder. Mod Pathol 2009; 22:70-95.