Epitelyal Ovel Tümörlerinin CD 34 ve Vonwillebrand Faktör ile İmmunohistokimyasal Yöntemle Değerlendirilmesi

Amaç: Endotel hücrelerinin CD34 ve vonWillebrand Faktör (Faktör VIII) gibi özel işaretleyiciler ile immunohistokimyasal yöntemle boyanarak mikro damar sayılması, tümör anjiyogenezini belirlemede kullanılan bir yöntemdir. Bu çalışmada, jinekolojik kanserler içinde 3. sıklıkla görülen ve en öldürücü olan epitelyal over tümörlerinin, normal over dokusu ile anjiyogenez açısından karşılaştırmalı olarak değerlendirilmesi amaçlanmıştır. Materyal-Metod: Çalışmada SSK Ege Doğumevi ve Kadın Hastalıkları Eğitim Hastanesinde opere edilen ve patoloji laboratuvarında tanı konulan toplam 60 vaka değerlendirildi. Olgulardan folliküler ve luteal evredeki normal over dokuları kontrol grubu; borderline-seröz, borderline-müsinöz, seröz adenokarsinoma ve müsinöz adenokarsinoma tanılı olgular ise çalışma grubu olarak belirlendi (n=10). Hastalardan elde edilen biopsiler formalin ile tespit edilerek rutin parafin takip protokolü uygulandı. Kesitler histolojik değerlendirme için hematoksileneosin ile, anjiyogenezi belirlemek için endotel işaretleyiciler CD34 ve vonWillebrand Faktör primer antikorları ile indirek immunoperoksidaz tekniği kullanılarak değerlendirildi. Damar yüzey dansiteleri ölçümü için, çalışma ve kontrol gruplarında mikro damar sayımları intersept gridi kullanılarak yapıldı. Elde edilen veriler istatistiksel olarak ANOVA testi ile değerlendirildi. Bulgular: Folliküler ve luteal evrede alınan normal over dokularında damar yüzey dansite ölçümleri arasında istatistiksel olarak farklılık gözlenmedi. Borderline ve adenokarsinom olgularında istatistiksel olarak kontrol grubuna göre artış saptandı. Buna ilaveten, damar yüzey dansitesinin müsinöz kanserlerde en fazla olduğu görüldü. Sonuç: Anjiyogenez, normal siklusda over ile endometriumda gözlenen follikülerluteal evre değişikliklerinde ve kadın üreme sistemi hastalıklarının birçoğunda etiyopatogenezde ön plandadır. Bu çalışmada da malign over tümörlerinde damar yüzey dansitesinin istatistiksel olarak arttığı ve bu artışın müsinöz over karsinomlarında daha belirgin olduğu görülmüştür. Anjiyogenezin yoğun olduğu olgularda tedaviye antianjiyogenik kemoterapinin eklenmesinin yararlı olabileceği düşünülmüştür.

Purpose: The staining of endothelial cells with specific markers such as CD34 and Factor VIII-Related Factor (vonWillebrand Factor) is a method used to detect angiogenesis of tumour. In this study, we aimed to evaluate the 3rd common type of gynecological cancer and fatal epithelial ovarian tumours, by using immunohistochemistry to investigate vascular surface density. Materials and methods: In this study, sixty patients who were operated at the SSK Aegean Maternity Hospital were evaluated. Ovarian specimens from women in follicular or luteal phases without ovarian pathology were investigated as a control group; specimens with borderline serous, borderline musinous, musinous adenocarsinoma, who had gone undergone laporoscopy were investigated as the study group (n= 10). Ovarian tissues were fixed in formaline and embedded in paraffin. Histological sections were immunostained with CD34 and vonWillebrand factor primary antibodies using indirect immunoperoxidase technique. Vascular surface densities in both study and control groups were evaluated with using intercept grid. Data were evaluated statistically with using ANOVA test. Results: The mean vascular surface density was not statistically different between the ovarium in follicular and in luteal phases. The mean vascular surface density was significantly higher in both borderline and malign ovarian carcinoma than control group. In addition, the mean vascular surface density was highest in the in musinous carcinoma. Conclusion: Angiogenesis plays a key role during follicular and luteal phases in normal menstrual cycle and etiopathogenesis of female reproductive system diseases. In this study, the vascular surface density was increased statistically in malign ovarian carcinoma, and it was higher in musinous ovarian carcinoma. Our results suggested that anti-angiogenic chemotherapy might be added to the treatment of ovarian carcinoma with increased angiogenesis. Key Words: angiogenesis, Epithelial ovarian tumour, hemistry immunohistoc

___

  • DiSaia PJ, Creaseman WT. Epithelial ovarian cancer. In: DiSaia PJ, Creasman WT, ed. Clinical Oncology. St. Louis: Mosby–Year Book. 1993: 333-425.
  • Scully RE. Common epithelial tumors of borderline malignancy (carcinoma of low potential): Bull Cancer 1982 : 69; 228.
  • Russell P. Surface epitelial-stromal tumors of ovary. In: Kurman RJ, ed: Blaustein’s Pathology of the Female Genital Tract. New York , 1994: 705.
  • Rosai J. Ackerman’s Surgical Pathology: 8th ed. Mosby. StLouis Misouri, 1995.
  • Hart WR, Norris HJ. Borderline and malignant tumors of the ovary: Cancer 1973; 31: 1031.
  • Atasü T, Aydınlı K: Jinekolojik Onkoloji, Logos Yayıncılık, İstanbul, 1999: 312-440.
  • Gordon JD, Schifren JL, Poulk RA, Taylor RN, Jaffe RB. Angiogenesis in the female reproductive tract: Obstet Gynecol Surv 1995; 50: 688-697.
  • Abulafia O, Triest WE, Sherer DM. Angiogenesis in malignancies of the female genital tract: Gynecol Oncol 1999; 72: 220-231.
  • Alvarez AA, Krigman HR, Whitaker RS, Dodge RK, Rodriguez GC. The prognostic significance of angiogenesis in epithelial ovarian carcinoma: Clin Cancer Res 1999; 5: 587-591.
  • Brown MR, Blanchette JO, Kohn EC. Angiogenesis in ovarian cancer: Baillieres Best Pract Res Clin Obstet Gynaecol 2000; 14: 901-918.
  • Hollingsworth HC, Kohn EC, Steinberg SM, Rothenberg ML, Merino MJ. Tumor angiogenesis in advanced stage ovarian carcinoma: Am J Pathol 1995; 147: 33-41.
  • Howard C.V, Reed M.G. Unbiased Sterology: Three dimensional measurement in microscopy. Bios Scientific Publishers, U.K. 1998: 116
  • Jaffe RB. Importance of angiogenesis in reproductive physiology: Semin Perinatol 2000; 24: 79-81.
  • Koblizek TI, Weiss C, Yancopoulos GD, Deutsch U, Risau W. Angiopoietin-1 induces sprouting angiogenesis in vitro: Curr Biol 1998; 8: 529-532.
  • Klagsbrun M, D’Amore D. Regulation of angiogenesis: Annu Rev Physiol 1991; 53: 217-239.
  • Strivastava A, Laidler P, Davies RP, Horgan K, Hughes LE. The prognostic significance of tumor vascularity in intermediate thickness (0.76-4mm thick) skin melanoma: Am J Pathol 1988; 133: 413-423.
  • Weidner N, Semple JP, Welch WR, Folkman J. Tumor angiogenesis and metastasis: correlation in invasive breast carcinoma: N Eng J Med 1991; 324: 1-8.
  • Dickinson AJ, Fox SB, Persad AA, Hollyee J, Sibley GN, Harris AL. Quantification of angiogenesis as an independent predictor of prognosis in invasive bladder cancer: Br J Urol 1994; 74: 762-766.
  • Weldher N, Carroll PR, Flax J, Blimenfeld W, Folkman J. Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma: Am J Pathol 1993; 143: 401-409.
  • Macchiarini P, Fontani G, Hardin MJ, Squartini F, Angeletti CA. Relation of neovascular to metastasis of non-small cell lung cancer: Lancet 1992; 340: 145-146.
  • Olivarez D, Wilbroght T, DeRiese W, Foster R, Reister T, Einhorn L. Neovascularization in clinical stage A testicular germ cell tumor prediction of metastatic disease: Cancer Res 1994; 54: 2880-2882.
  • Wiggins DL, Granai CO, Steinhoff MM, Calabrewsi P. Tumor angiogenesis as a prognostic factor in cervical carcinoma: Gynecol Oncol 1993; 56: 353-356.
  • Kirschner CV, Alanis-Amezcua JM, Martin VG, Luna N, Morgan E, Yang JJ. Angiogenesis factor in endometrial carcinoma: a new prognostic indicator: Am J Obstet Gynecol 1996; 174: 1879-1884.
  • Heimburg S, Oehler MK, Papadopoulos T, Caffier H, Kristen P, Dietl J. Prognostic relevance of the endothelial marker CD34 in ovarian cancer: Anticancer Res 1999; 19: 2527-2529.
  • Obermair A, Wasicky R, Kaider A, Preyer O, Losch A, Leodolter S, Kolbl H. Prognostic significance of tumor angiogenesis in epithelial ovarian cancer: Cancer Lett 1999; 138: 175-182.
  • Gasparini G, Bonoldi E, Viale G, Verderio P, Boracchi P, Panizzoni GA, Radaelli U, Di Bacco A, Guglielmi RB, Bevilacqua P. Prognostic and predictive value of tumour angiogenesis in ovarian carcinomas: Int J Cancer 1996; 69: 205-211.
  • Brustmann H, Riss P, Naude S. The relevance of angiogenesis in benign and malignant epithelial tumors of theovary: a quantitative histologic study: Gynecol Oncol 1997; 67: 20-26.
  • Abulafia O, Ruiz JE, Holcomb K, Dimaio TM, Lee YC, Sherer DM. Angiogenesis in early-invasive and low-malignant-potential epithelial ovarian carcinoma: Obstet Gynecol 2000; 95: 548-552.
  • Schoell WM, Pieber D, Reich O, Lahousen M, Janicek M, Guecer F, Winter R. Tumor angiogenesis as a prognostic factor in ovarian carcinoma: quantification of endothelial immunoreactivity by image analysis. Cancer 1997; 80: 2257-2262.