Prognostic significance of ezrin, Ki-67 and CD34 expressions in non-small cell carcinoma of the lung metastazing to the central nevrous cystem

Abstract

Keywords

• -

Merkez sinir sistemine metastazı yapan küçük hücreli dışı akciğer tümörlerinde ezrin, Ki-67 ve CD34 ekspresyonunun prognostik önemi

Abstract

Amaç: Akciğer karsinomu en yaygın malignitelerden biridir ve biyolojik davranışı tam olarak tanımlanamamıştır. Prognostik faktörlerin bilinmesi en etkin sağaltımın seçilmesinde çok önemlidir. Bu amaçla, bilinen prog-nostik faktörlerden Ki- 67 ve CD 34 ile daha az bilinen, malign hücrelerin invaziv davranışında önemli rol oyna-dığı düşünülen ezrinin, küçük hücreli dışı akciğer karsi-nomlarındaki prognostik önemi araştırılmıştır. Gereç ve yöntem: Çalışmanın materyalini 19’u merkez sinir sistemine (MSS) metastaz yapmayan toplam 35 küçük hücreli dışı akciğer karsinomu oluşturmaktadır. Her iki grupta tümör volümleri ve hasta sağkalımları ayrı ayrı değerlendirilirken, bunların ezrin, Ki-67 ve CD 34 immün reaktiviteleri ile korelasyonları araştırılmıştır. Bulgular: İki grup arasında karşılaştırılan parametreler ve immün boyalar açısından anlamlı bir ilişki saptanmamıştır. Sonuç: Bulgularımız, çalışılan olgu sayısının nispeten az oluşuna bağlı olabilir. Ayrıca, seçilen materyallerin bir kısmı bronkoskopik biyopsi, bir kısmı ise rezeksiyon materyalidir. Küçük hücreli dışı akciğer karsinomlarında tümör içi heterojenite önemli bir özelliktir ve bronkoskopik biyopsiler tümörün tamamını temsil etmez. Yine özellikle ezrin ile ilgili çok az kaynak bilgisi olup, çelişkili sonuçlara ulaşılmıştır. Daha ileri çalışmalarda, verilerin standart tutulması ve geniş dizilerde çalışılması, sonuçların daha güvenilir olmasına katkıda bulunacaktır

Keywords

• Ezrin, Ki-67, CD 34, prognoz, akciğer karsinomu

References

1. Soomro IN, Holmes J, Whimster WF. Predicting prognosis in lung cancer: use of proliferating marker, Ki-67 mono- clonal antibody. J Pak Med Assoc 1990; 48(3): 66-9.
2. Dar-Bin Shieh, John Godleski, James E, Herndon II, Toshifumi Azuma, Harriet Mercer, David J. Sugarbaker, et al. Cell motility as a prognostic factor in stage I nonsmall cell lung carcinoma. Cancer 1999; 85: 47-57.
3. Rosai J. Respiratory Tract, Ackerman’s Surgical Pathology, eighth ed, St. Louis: Mosby, 1996; 372-373.
4. Rubin E, Farber JL. Pathology, third ed. Philadelphia: Lippincott-Raven, 1999.
5. Nestl A, Von Stein OD, Zatloukal K, Thies WG, Herrlich P, Hofman M, et al. Gene expression patterns associated with the metastatic phenotype in rodent and human tumors. Cancer Res Feb 1999; 15; 61(4); 1569-77.
6. Kathrin D, Geiger, Peter Stoldt, Wolfgang Schlote and Amin Derouiche. Ezrin immunreactivity is associated with increasing malignancy of astrocytic tumors but is absent in oligodendrogliomas. Am J Pathol 2000; 157.
7. Francesc Granes, Jesus Mariano Urena, Nativitat Roca- mora and Senen Vilaro. Ezrin links syndecan-2 to the cytoskelaton. J Cell Scien 2000; 113: 1267-1276.
8. Anthony Bretscher, David Reczek and Mark Berryman. Ezrin: a protein requiring conformational activation to link microfilaments to the plasma membrane in the assembly of cell surface structures. J Cell Scien 1997; 110, 3011-3018.

9. Hiscox S, Jiang WG. Ezrin regulates cell-cell and cell- matrix adhesion, a possible role with E-cadherine/beta- catenin. J Cell Sci 1999; 112 (18): 3081-90.
10. Tokunou M, Niki T, Saitoh Y, Imamura H, Sakamoto M, Hirohashi S. Altered expression of the ERM proteins in lung adenocarcinoma. Lab Invest 2000; 80(11): 1643-5.
11. Wolfgang Wick, Cornelia Grimmel, Christine Wild-Bode, Michael Platten, Monique Arpin, and Michael Weller. Ezrin- dependent promotion of glioma cell clonogenicity, motility, and invasion mediated by BCL-2 and transforming growth factor-ß2. J Neuroscien 2001; 21(10): 3360-3368.
12. Christophe Andreoli, Marianne Martin, Roland Le Borgne, Hubert Reggio and Paul Mangeat. Ezrin has properties to self-associate at the plasma membrane. J Cell Scien 1994; 107: 2509-2521.
13. Margaret Magendantz, Michael D. Henry, Arthur Lander and Frank Solomon. Interdomain interactions of radixin in vitro. The J Biol Chem 1995; 270(43): 25324-25327.
14. Crepaldi T, Gautreau A, Comoglio P, Louvard D, Arpin M. Ezrin is an effector of hepatocyte growth factor-mediated migration and morphogenesis in epithelial cells. J Cell Biol 1997; 138: 423-434.
15. Yen K. Tran, Bögler O, Gorse KM, Wieland I, Green MR, and NewshamIF. A novel member of the NF2/ERM/4.1 superfamily with growth suppressing properties in lung cancer. Cancer Res 1999; 59: 35-43.
16. Dransfield DT, Bradford AJ, Smith J, Martin M, Roy C, Mangeat PH et al. Ezrin is a cyclic AMP-dependent protein kinase anchoring protein.The EMBO J 1997; 16: 35- 43.
17. Vaheri A, Carpen O, Heiska L, Helander TS, Jaaskelainen J, Majander-Nordenswan et al. The ezrin protein family: membrane-cytoskeleton interactions and disease asso- ciations. Curr Cell Biol 1997; 9: 659-666.
18. Bretscher A. Regülation of cortical structure by the ezrin- radixin-moesin protein family. Curr Opin Cell Biol 1999; 11: 109-116.
19. Mangeat P, Roy C and Martin M. ERM proteins in cell adhesion and membrane dynamics. Trends Cell Biol 1999; 9: 187-192.
20. Yonemura S, Tsukita S, Tsukita S. Direct involvement of ezrin/radixin /moesin (ERM)-binding membrane proteins in the organisation of microvilli in collaboration with activated ERM proteins. J Cell Biol 1999; 145: 1497-1509.
21. Naoaki Akisawa, Isao Nishimori, Takeshi Iwamura, Saburo Onishi and Michael A. Hollingsworth. High levels of ezrin expressed by human pancreatic adenocarcinoma cell lines with high metastatic potential. Bioch and Biophys Research Communications 1999; 258, 395-400.
22. Nguyen VN, Mirejovsky P, Mirejovsky T, Melinova L and Mandys V. Expression of cyclinD1, Ki-67 and PCNA in non-small cell lung cancer; Prognostic significance and comparison with P53 and bcl-2. Acta Histochem 2000; 102(3): 323-38.
23. Viberti L, Papotti M, Abbona GC, Celano A, Filosso PL and Bussolati G. Value of Ki-67 immunostaining in preoperative biopsies of carcinomas of the lung. Hum Pathol 1997; 28(2): 189-92.
24. Shiba M, Kohno H, Kakizawa K, Lizasa T, Otsuji M, Saitoh Y et al. Ki-67 immunostaining and other prognostic factors including tobacco smoking in patients with resected non- small cell lung carcinoma. Cancer 2000; 89(7): 1457-65.
25. Demarchi LMMF, Reis MM, Pinheiro SA, Ferhat C, Taka- gaki TY, Beyruti R, et al. Prognostic values of stromal proportion and PCNA, Ki-67 and p53 proteins in patients with resected Adenocarcinoma of the Lung. Mod Pathol 2000; 13(5): 511-520.
26. Ishiwata N, Jinn Y, Tsukada Y, Inase N, Ichioka M and Yoshizawa Y. Relationship between apoptosis and im- munohistochemical staining for proliferating cell nuclear antigen and Ki-67 in non-smal cell lung cancer. Anticancer Res 2000; 20(3A): 1445-50.
27. Kawana H, Tamaru J, Tanaka T, Hirai A, Saito Y, Kitagawa M, et al. Role of p27 and Cyclin-dependent kinase 2 in the proliferation of non-small cell lung cancer. Am J Pathol 1998; 153: 505-513.
28. Salven P, Lymboussaki A, Heikkila P, Jaaskela-Saari H, Enholm B, Aase K, et al. Vascular endothelial growth factors VEGF-B are expressed in human tumors. Am J Pathol 1998; 153: 103-108.
29. Lauren J, Gunji Y and Alitalo K.. Is Angiopoietin-2 necessary for the initiation of tumor angiogenesis? Am J Pathol 1998; 153: 1333-1339.
30. Risau W. Mechanisms of angiogenesis. Nature 1997; 386: 671-674.
31. Matsuyama K, Chiba Y, Sasaki M, Tanaka H, Muraoka R, Tanigawa N. Tumor angiogenesis as a prognostic marker, in operable non-small cell lung cancer. Ann Thorac Surg 1998; 65: 1405-9.
32. Weidner N. Intratumor microvessel density as a prognostic factor in cancer. Am J Pathol 1995; 147: 9.
33. Harpole DH, Richards WG, Herndon JE II and DJ Sugar- baker. Angiogenesis and molecular biologic substaging in patients with stage I non-small cell lung cancer. Ann Thorac Surg 1996; 61: 1470-6.
34. Fontanini G, Pingitore R, Bigini D, Vignati S, Pepe S, Ruggiero A et al. Growth fraction in non-small cell lung cancer estimated by proliferating cell nuclear antigen and comparison with Ki-67 labeling and DNA flow cytometry data. Am J Pathol 1992; 141: 285-1290.
35. Ishida H, Irie K, Itoh T, Furukawa T, Tokunaga O. The prognostic significance of p53 and bcl-2 expression in lung adenocarcinoma and its correlation with Ki-67 growth fraction. Cancer 1997; 80: 1034-4.
36. Wintzer HO, Zipfel I, Schulte-Mönting J, Hellerich U and von Kleist S. Ki-67 immunostaining in human breast tumors and its relationship to prognosis. Cancer 1991; 67: 421-8.
37. Quin CM, Wright NA. The clinical assesment of prolifera- tion and growth in human tumors: evaluation of methods and applications as prognostic variables. J Pathol 1990; 160: 93-102.
38. Mehdi SA, Etzell JE, Newman NB, Weidner N, Kohman LJ and Graziano SL. Prognostic significance of Ki-67 immunostaining and symptoms in resected stage I and II non-small cell lung cancer. Lung Cancer 1998; 20: 99-108.
39. Brown DC, Gatter KC. Monoclonal antibody Ki-67: its use in histopathology. Histopathology 1990; 17, 489-503.
40. Weidner N, Carrol PR, Flax J, Blumenfeld Wand, Folkman J. Tumor angiogenesis correlates with metastasis in in- vasive prostate carcinoma. Am J Pathol 1993; 143: 401-409.
41. Yamazaki K, Abe S, Takekawa H, Sukoh N, Watanabe N, Ogura S, et al. Tumor angiogenesis in human lung adenocarcinoma. Cancer 1994; 74: 2245-50.
42. Dazzi C, Cariello A, Maioli P, Solaini L, Scarpi E, Rosti G, et al. Prognostic and predictive value of intratumoral mic- rovessels density in operable non-small-cell lung cancer. Lung Cancer 1999; 24: 81-88.
43. Macchiarini P, Fontanini G, Dulmet E, de Montpreville V, Chapelier AR, Cerrina J, et al. Angiogenesis: an indicator of metastasis in non small cell lung cancer invading the thoracic inlet. Ann Thorac Surg 1994; 57: 1534-1539.
44. Ohtani K, Sakamato H, Rutherford T, Chen Z, Satoh K, Naftolin F. Ezrin, a membrane-cytoskeletal linking protein, is involved in the process of invasion of endometrial cancer cells. Cancer Lett 1999; 147(1-2): 31- 8.
45. Simony J, Pujol JL, Radal M, Ursule E, Michel FB, Pujol H. In situ evaluation of growth fraction determined by mono- clonal antibody Ki-67 and ploidy in surgically resected non-small cell lung cancers. Cancer Res 1990; 50(14): 4382-7.
46. Bubb RS, Komaki R, Hachiya T, Milas I, Ro JY, Langford L et al. Association of Ki-67, p53 and bcl-2 expression of the primary non-small-cell lung cancer lesion with brain metastatic lesion. Int J Radiat Oncol Biol Phys 2002; 53(5): 1216-24.
47. Giatromanolaki A, Koukourakis M, O’Byrne K, Fox S, Whitehouse R, Talbot D.C, et al. Prognostic value of an- giogenesis in operable non-small cell lung cancer. J Pathol 1996; 179: 80-8.