Survivin, Possible Marker and Prognostic Factor in Oral Squamous Cell Carcinomas

  • Kim, Young-Youn (Department of Oral and Maxillofacial Surgery, Dental Research Institute, College of Dentistry, Seoul National University) ;
  • Kim, Myung-Jin (Department of Oral and Maxillofacial Surgery, Dental Research Institute, College of Dentistry, Seoul National University) ;
  • Choi, Keum-Kang (Department of Oral and Maxillofacial Surgery, Dental Research Institute, College of Dentistry, Seoul National University) ;
  • Hong, Seong-Doo (Department of Oral Oncology, Dental Research Institute, College of Dentistry, Seoul National University) ;
  • Myoung, Hoon (Department of Oral and Maxillofacial Surgery, Dental Research Institute, College of Dentistry, Seoul National University)
  • Published : 2008.02.29

Abstract

Survivin is a member of the inhibitors of apoptosis (IAP) family that have been known to inhibit activated caspases in apoptosis. In contrast to most IAP family members, survivin mRNA is expressed during fetal development, is not found in normal adult tissues and is overexpressed again in the cancer. Though survivin expression has been documented in most human cancers, little is known about its expression in OSCC and its potential value as a predictor of cancer survival. The purpose of this study was to investigate survivin expression in OSCC and to evaluate its value as a prognostic marker. We evaluated survivin expressions in cancer lines and OSCC samples and investigated the relationships between survivin expressions and clini-co-pathological parameters including stage, differentiation, proliferation, lymph node metastasis, blood vessel density, and gelatinolytic activity. With immunohistochemistry, we analyzed survivin expression in 38 OSCCs. Patients' clinico-pathological parameters and their survival rate were analyzed to reveal their correlations with Survivin expressions. We cultured oral cancer cell lines and evaluated the correlation between gelatinolytic activities and survivin expressions of them. Survivin protein was observed both in nuclei and cytoplasm of tumor specimens while little or not observed in normal gingival mucosal tissues. Additionally, survivin expressions were correlated with lymph node metastasis, tumor proliferation and survival rate. Survivin expression was observed in 100% of 38 samples of OSCC and its expression levels are statistically associated with the proliferative activity of the tumors, lymph node metastasis and the survival of the patients. Based on these results, survivin is commonly expressed in OSCC and may thus provide valuable prognostic information related with lymph node metastasis, proliferation and survival rate as well as a potential therapeutic target in OSCC.

Keywords

References

  1. Pisani P, Parkin DM, Bray F, Ferlay J: Estimates of the worldwide mortality from 25 cancers in 1990. Int J Cancer 1999;83:18-29
  2. Schliephake H: Prognostic relevance of molecular markers of oral cancer - a review. Int J Oral Maxillofac Surg 2003;32:233-45 https://doi.org/10.1054/ijom.2002.0383
  3. Friedlander PL: The use of genetic markers in the clinical care of patients with head and neck cancer. Arch Otolaryngol Head Neck Surg 2003;129:363-6 https://doi.org/10.1001/archotol.129.3.363
  4. Reed JC: The survivin saga goes in vivo. J Clin Invest 2001;108:965-9 https://doi.org/10.1172/JCI14123
  5. Ambrosini G, Adida C, Sirugo G, Altieri DC: Induction of apoptosis and inhibition of cell proliferation by survivin gene targeting. J Biol Chem 1998; 273: 461-6
  6. LaCasse E, Baird S, Korneluk RG, MacKenzie AE: The inhibitor of apoptosis (IAPs) and their emerging role in cancer. Oncogene 1998;17:3247-59 https://doi.org/10.1038/sj.onc.1202569
  7. Deveraux QK, Reed JC: IAP family proteins - suppressors of apoptosis. Genes Dev 1999;13:239-52 https://doi.org/10.1101/gad.13.3.239
  8. Shin S, Sung BJ, Cho YS, Kim HJ, Ha NC, Hwang JI, Chung CW, Jung YK, Oh BH: An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and ?7. Biochemistry 2001; 40:1117-23 https://doi.org/10.1021/bi001603q
  9. O'Connor DS, Grossman D, Plescia J, Li F, Zhang H, Villa A, Tognin S, Marchisio PC, Altieri DC: Regulation of apoptosis at cell division by p34cdc2 phosphorylation of surviving. Proc Natl Acad Sci USA, 2000;97:13103-7
  10. Swana HS, Grossman D, Anthony JN, Weiss RM, Altieri DC: Tumor content of the antiapoptosis molecule survivin and recurrence of bladder cancer. N Engl J Med 1999;341:452-3 https://doi.org/10.1056/NEJM199908053410614
  11. Adida C, Haioun C, Gaulard P, Lepage E, Morel P, Briere J, Dombret H, Reyes F, Diebold J, Gisselbrecht C, Salles G, Altieri DC, Molina TJ: Prognostic significance of survivin expression in diffuse large B-cell lymphomas. Blood 2000;96:1921-5
  12. Kawasaki H, Altieri DC, Lu CD, Toyoda M, Tenjo T, Tanigawa N: Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer. Cancer Res 1998;58:5071-4
  13. Ito T, Shiraki K, Sugimoto K, Yamanaka T, Fujikawa K, Ito M: Survivin promotes cell proliferation in human hepatocellular carcinoma. Hepatology 2000;31:1080-5 https://doi.org/10.1053/he.2000.6496
  14. Nakagawara A: Molecular basis of spontaneous regression of neuroblastoma: role of neurotrophic signals and genetic abnormalities. Hum Cell 1998;11:115-24
  15. Monzo M, Rosell R, Felip E, Astudillo J, Sanchez JJ, Maestre J, Martin C, Font A, Barnadas A, Abad A: A novel antiapoptosis gene: reexpression of survivin messenger RNA as a prognosis marker in nonsmall-cell lung cancers. J Clin Oncol 1999;17:2100-4 https://doi.org/10.1200/JCO.1999.17.7.2100
  16. Satoh K, Kaneko K, Hirota M, Masamune A, Satoh A, Shimosegawa T: Expression of survivin is correlated with cancer cell apoptosis and is involved in the development of human pancreatic duct cell tumors, Cancer 2001;92:271-8 https://doi.org/10.1002/1097-0142(20010715)92:2<271::AID-CNCR1319>3.0.CO;2-0
  17. Xing N, Qian J, Bostwick D, Bergstralh E, Young CY: Neuroendocrine cells in human prostate over-express the anti-apoptosis protein surviving. Prostate 2001;48:7-15 https://doi.org/10.1002/pros.1076
  18. Takamizawa S, Scott D, Wen J, Grundy P, Bishop W, Kimura K, Sandler A: The survivin : fas ratio in pediatric renal tumors J Pediatr Surg 2001;36:37-42 https://doi.org/10.1053/jpsu.2001.20000
  19. Okada E, Murai Y, Matsui K, Isizawa S, Cheng C, Masuda M, Tacano Y: Survivin expression in tumor cell nuclei is predictive of a favorable prognosis in gastric cancer patients. Cancer Lett 2001;163:109-16 https://doi.org/10.1016/S0304-3835(00)00677-7
  20. Noguchi N, Kawashiri K, Tanaka A, Kato K, Nakaya H: Effects of fibroblast growth inhibitor on proliferation and metastasis of oral squamous cell carcinoma. Oral Oncol 2003;39:240-7 https://doi.org/10.1016/S1368-8375(02)00092-1
  21. Bosari S: Microvessel quantitation and prognosis in invasive breast carcinoma. Hum Pathol 1992;23:755-61 https://doi.org/10.1016/0046-8177(92)90344-3
  22. Kennedy SM, O'Driscoll L, Purcell R, Fitz-Simons N, McDermott EW, Hill AD: Prognostic importance of survivin in breast cancer. Br J Cancer 2003;88:1077-83 https://doi.org/10.1038/sj.bjc.6600776
  23. Hong SD, Hong SP, Lee JI, Lim CY: Expression of matrix metalloproteinase-2 and -9 in oral squamous cell carcinomas with regard to the metastatic potential. Oral Oncol 2000;36:207-13 https://doi.org/10.1016/S1368-8375(99)00088-3
  24. Myoung H, Hong SP, Lee JI, Lim CY: Anti-cancer effect of genistein in oral squamous cell carcinoma with respect to angiogenesis and in vitro invasion. Cancer Sci 2003;94:215-20 https://doi.org/10.1111/j.1349-7006.2003.tb01422.x
  25. Ambrosini G, Adida C, Altieri DC: A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med 1997;3:917-21 https://doi.org/10.1038/nm0897-917
  26. Muzio LL, Staibano S, Pannone G, Mignogna MD, Mariggio A, Salvatore G, Chieffi P, Tramontano D, Rosa GD, Altieri DC: Expression of the Apoptosis Inhibitor survivin in Aggressive Squamous Cell Carcinoma. Experimental and Molecular Pathology 2001;70:249-54 https://doi.org/10.1006/exmp.2001.2367
  27. Miyachi K, Sasaki K, Onodera S, Taguchi T, Nagamachi M, Kaneko H, Sunagawa M: Correlation between survivin mRNA expression and lymph node metastasis in gastric cancer. Gastric Cancer 2003;6:217-24 https://doi.org/10.1007/s10120-003-0255-2
  28. O'Driscoll L, Linehan R, Kennedy M, Cronin D, Purcell R, Glynn S: Lack of prognostic significance of survivin, survivin-deltaEx3, survivin-2B, galectin-3, bag-1, bax-alpha and MRP-1 mRNAs in breast cancer. Cancer Lett 2003;201:225-36
  29. Adida C, Recher C, Raffoux E, Daniel MT, Taksin AL, Rousselot P, Sigaux F, Degos L, Altieri DC, Dombret H: Expression and prognostic significance of survivin in de novo acute myeloid leukaemia. Br J Haematol 2000;111:196-203 https://doi.org/10.1046/j.1365-2141.2000.02328.x
  30. Frost M, Jarboe EA, Orlicky D, Gianani R, Thompson LC, Enomoto T, Shroyer TS: Immunohistochemical localization of survivin in benign cervical mucosa, cervical dysplasia, and invasive squamous cell carcinoma. Am J Clin Pathol 2002;117:738-44 https://doi.org/10.1309/6V09-38K3-JQ40-UR50
  31. Rodriguez JA, Span SW, Ferreira CG, Kruyt FA, Giaccone G: CRM1-mediated nuclear export determines the cytoplasmic localization of the antiapoptotic protein surviving. Exp Cell Res 2002; 275:44-53 https://doi.org/10.1006/excr.2002.5492
  32. Konno R, Yamakawa H, Utsunomiya H, Ito K, Sato S, Yajima A: Expression of survivin and Bcl-2 in the normal human endometrium. Mol Hum Report 2000;6:529-34 https://doi.org/10.1093/molehr/6.6.529
  33. Li F, Ambrosini G, Chu EY, Plescia J, Tognin S, Marchisio PC, Altieri DC: Anti-apoptosis gene, survivin, and prognosis, Control of apoptosis and mitotic spindle checkpoint by surviving. Nature 1998;396:580-4 https://doi.org/10.1038/25141
  34. Uren AG, Wong L, Pakusch M, Fowler KJ, Burrows FJ, Vaux DL, Choo KH: Survivin and the inner centromere protein INCENP show similar cell-cycle localization and gene knockout phenotype. Curr Biol 2000;10:1319-28 https://doi.org/10.1016/S0960-9822(00)00769-7
  35. Altieri DC: The molecular basis and potential role of survivin in cancer diagnosis and therapy. Trends Mol Med 2001;7:542-7 https://doi.org/10.1016/S1471-4914(01)02243-2
  36. Hedley DW, Friedlander ML, Taylor IW, Rugg CA, Musgrove EA: Method for analysis of cellular DNA content of paraffin-embedded pathological material using flowcytometry. J Histochem Cytochem 1983;31:1333-5 https://doi.org/10.1177/31.11.6619538
  37. Grossman D, Kim PJ, Schechner JS, Altieri DC: Inhibition of melanoma tumor growth in vivo by survivin targeting. Proc Natl Acad Sci USA 2001;98:635-40
  38. Suzuki A, Hayashida M, Ito T, Kawano H, Nakano T, Miura M, Akahane K, Shiraki K: Survivin initiates cell cycle entry by the competitive interaction with Cdk4/p16(INK4a) and Cdk2/cyclin E complex activation. Oncogene 2000;19:3225-34 https://doi.org/10.1038/sj.onc.1203665
  39. Adida C, Crotty PL, McGrath J, Berrebi D, Diebold D, Altieri DC: Developmentally regulated expression of the novel cancer anti-apoptosis gene survivin in human and mouse differentiation. Am J Pathol 1998;152:43-9
  40. Liotta LA, Rao CN, Barsky SH: Tumor invasion and the extracellular matrix. Lab Invest 1983;49:636-49
  41. Wyllie AH, Bellamy COC, Bubb AR, Clarke AR, Corbet S, Curtis L: Apoptosis and carcinogenesis. Br J Cancer 1999;80:34-7
  42. Sierra A, Castellsague X, Escobedo A, Lloveras B, Ramnrez MG, Moreno A: Bcl-2 with loss of apoptosis allows accumulation of genetic alterations: a pathway to metastatic progression in human breast cancer. Int J Cancer 2000;89:142-7 https://doi.org/10.1002/(SICI)1097-0215(20000320)89:2<142::AID-IJC7>3.0.CO;2-B
  43. Glinsky GV, Glinsky VV: Apoptosis and metastasis: a superior resistance of metastatic cancer cells to programmed cell death. Cancer Lett 1996;101:43-51 https://doi.org/10.1016/0304-3835(96)04112-2
  44. Glinsky GV, Glinsky VV, Ivanova AB, Hueser CJ: Apoptosis and metastasis: increased apoptosis resistance of metastatic cancer cells is associated with the profound deficiency of apoptosis execution mechanisms. Cancer Lett 1997;115:185-93 https://doi.org/10.1016/S0304-3835(97)04738-1
  45. Kato J, Kuwabara Y, Mitani M, Shinoda N, Sato A, Toyama T, Mitsui A, Nishiwaki T, Moriyama S, Kudo J, Fujii Y: Expression of survivin in esophageal cancer: correlation with the prognosis and response to chemotherapy. Int J Cancer 2001;95:92-5 https://doi.org/10.1002/1097-0215(20010320)95:2<92::AID-IJC1016>3.0.CO;2-9
  46. Yoshida H, Ishiko O, Sumi T, Matsumoto Y, Ogita S: Survivin, bcl-2 and matrix metalloproteinase-2 enhance progression of clear cell- and serous-type ovarian carcinomas. Int J Oncol 2001;19:537-42
  47. Xiangming C, Hokita S, Natsugoe S, Tanabe G, Baba M, Takao S: Angiogenesis as an unfavorable factor related to lymph node metastasis in early gastric cancer. Ann Surg Oncol 1998;5:585-9 https://doi.org/10.1007/BF02303826
  48. Maeda K, Chung YS, Ogawa Y, Takatsuka S, Kang SM, Ogawa M: Prognostic value of vascular endothelial growth factor expression in gastric carcinoma. Cancer 1996; 77:858-63 https://doi.org/10.1002/(SICI)1097-0142(19960301)77:5<858::AID-CNCR8>3.0.CO;2-A
  49. Tran J, Rak J, Sheehan C, Saibil SD, LaCasse E, Korneluk RG: Marked induction of the IAP family antiapoptotic proteins survivin and XIAP by VEGF in vascular endothelial cells. Biochem Biophys Res Commun 1999;264:781-8 https://doi.org/10.1006/bbrc.1999.1589